The relationship of prenatal ethanol exposure and anxiety-related behaviors and central androgen receptor and vasopressin expression in adult male mandarin voles.

PubMed

He, F

2014-04-25

Prenatal exposure to ethanol has been shown to increase the risk of anxiety in offspring. Here, we tested the effect of prenatal ethanol exposure on adult male mandarin voles (Microtus mandarinus). We examined anxiety-like behavior in the open field and elevated plus-maze tests in males exposed to ethanol prenatally. One control group was not exposed to ethanol or saline, while another control group was exposed to saline. At the age of 90days, males were tested and levels of serum testosterone, androgen receptor immunoreactive neurons (AR-IRs) and arginine vasopressin immunoreactive neurons (AVP-IRs) were measured. Animals exposed to ethanol spent less time in the center of the chamber, covered less distance and conducted fewer crossings in the open-field test. These animals also spent less time and conducted fewer crossings in the open arms. However, they spent more time and made more entries in the closed arms, and traveled less total distance during the elevated plus-maze test, compared to the control voles. Serum T was lower in the ethanol group, and the AR-IR number in the bed nucleus of the stria terminalis (BNST), medial preoptic area (mPOA) and medial amygdaloid nucleus (MeA) was significantly lower. The number of AVP-IRs in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the ethanol group was higher than that of the control groups. Our findings suggest that prenatal ethanol exposure may lead to reduced serum T levels, decreased AR and increased AVP in the CNS and result in the development of anxiety-like behaviors. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Gastroprotective effects of Corchorus olitorius leaf extract against ethanol-induced gastric mucosal hemorrhagic lesions in rats.

PubMed

Al Batran, Rami; Al-Bayaty, Fouad; Abdulla, Mahmood Ameen; Al-Obaidi, Mazen M Jamil; Hajrezaei, Maryam; Hassandarvish, Pouya; Fouad, Mustafa; Golbabapour, Shahram; Talaee, Samaneh

2013-08-01

Corchorus olitorius is a medicinal plant traditionally utilized as an antifertility, anti-convulsive, and purgative agent. This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C. olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats. The rats were divided into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20 mg/kg omeprazole), and four experimental groups (50, 100, 200, or 400 mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical evaluations. Compared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P < 0.05) and reduced (P < 0.05), respectively. In addition to the histologic analyses (HE and periodic acid-Schiff staining), immunohistochemistry confirmed the protection through the upregulation of Hsp70 and the downregulation of Bax proteins. The gastroprotection of the experimental groups was comparable to that of the reference control medicine omeprazole. Our study reports the gastroprotective property of an ethanolic extract of C. olitorius against ethanol-induced gastric mucosal hemorrhagic lesions in rats. © 2013 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Gastroprotective effects of Corchorus olitorius leaf extract against ethanol-induced gastric mucosal hemorrhagic lesions in rats

PubMed Central

Al Batran, Rami; Al-Bayaty, Fouad; Ameen Abdulla, Mahmood; Jamil Al-Obaidi, Mazen M; Hajrezaei, Maryam; Hassandarvish, Pouya; Fouad, Mustafa; Golbabapour, Shahram; Talaee, Samaneh

2013-01-01

Background and AimCorchorus olitorius is a medicinal plant traditionally utilized as an antifertility, anti-convulsive, and purgative agent. This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C. olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats. MethodsThe rats were divided into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20 mg/kg omeprazole), and four experimental groups (50, 100, 200, or 400 mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical evaluations. ResultsCompared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P < 0.05) and reduced (P < 0.05), respectively. In addition to the histologic analyses (HE and periodic acid-Schiff staining), immunohistochemistry confirmed the protection through the upregulation of Hsp70 and the downregulation of Bax proteins. The gastroprotection of the experimental groups was comparable to that of the reference control medicine omeprazole. ConclusionsOur study reports the gastroprotective property of an ethanolic extract of C. olitorius against ethanol-induced gastric mucosal hemorrhagic lesions in rats. PMID:23611708

Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

PubMed

Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

2016-12-01

Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Differential effects of context on psychomotor sensitization to ethanol and cocaine.

PubMed

Didone, Vincent; Quoilin, Caroline; Dieupart, Julie; Tirelli, Ezio; Quertemont, Etienne

2016-04-01

Repeated drug injections lead to sensitization of their stimulant effects in mice, a phenomenon sometimes referred to as drug psychomotor sensitization. Previous studies showed that sensitization to cocaine is context dependent as its expression is reduced in an environment that was not paired with cocaine administration. In contrast, the effects of the test context on ethanol sensitization remain unclear. In the present study, female OF1 mice were repeatedly injected with 1.5 g/kg ethanol to test for both the effects of context novelty/familiarity and association on ethanol sensitization. A first group of mice was extensively pre-exposed to the test context before ethanol sensitization and ethanol injections were paired with the test context (familiar and paired group). A second group was not pre-exposed to the test context, but ethanol injections were paired with the test context (nonfamiliar and paired group). Finally, a third group of mice was not pre-exposed to the test context and ethanol was repeatedly injected in the home cage (unpaired group). Control groups were similarly exposed to the test context, but were injected with saline. In a second experiment, cocaine was used as a positive control. The same behavioral procedure was used, except that mice were injected with 10 mg/kg cocaine instead of ethanol. The results show a differential involvement of the test context in the sensitization to ethanol and cocaine. Cocaine sensitization is strongly context dependent and is not expressed in the unpaired group. In contrast, the expression of ethanol sensitization is independent of the context in which it was administered, but is strongly affected by the relative novelty/familiarity of the environment. Extensive pre-exposure to the test context prevented the expression of ethanol sensitization. One possible explanation is that expression of ethanol sensitization requires an arousing environment.

Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

PubMed Central

Sena, Maria Clécia P; Nunes, Fabíola C; Stiebbe Salvadori, Mirian G S; Carvalho, Cleyton Charles D; Morais, Liana Clébia S L; Braga, Valdir A

2011-01-01

OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n  =  16) had access to sugarcane spirit + distilled water, the mice in Group B (n  =  15) had access to ethanol + distilled water, and the mice in Group C (control, n  =  14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 ± 8 vs. 7 ± 2 s, n  =  9) or sugarcane spirit (36 ± 9 vs. 7 ± 2 s, n  =  9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 ± 1 for the control group, 27 ± 2 for the ethanol group, and 31 ± 3 for the sugarcane-spirit group; n  =  9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 ± 0.17 for the control group and 2.67 ± 0.17 for the sugarcane spirit group; n  =  8 for each group). CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice. PMID:21789394

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Zhenhua

Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanolmore » by gavage (5 g/kg, 25% ethanol w/v) daily for 3 days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3 days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas. - Highlights: • Chronic plus binge alcohol drinking causes more pancreatic injury. • Chronic plus binge alcohol drinking induces more pancreatic inflammation. • Chronic plus binge alcohol causes more endoplasmic reticulum stress and oxidative stress.« less

Ethanol prefermentation of food waste in sequencing batch methane fermentation for improved buffering capacity and microbial community analysis.

PubMed

Yu, Miao; Wu, Chuanfu; Wang, Qunhui; Sun, Xiaohong; Ren, Yuanyuan; Li, Yu-You

2018-01-01

This study investigates the effects of ethanol prefermentation (EP) on methane fermentation. Yeast was added to the substrate for EP in the sequencing batch methane fermentation of food waste. An Illumina MiSeq high-throughput sequencing system was used to analyze changes in the microbial community. Methane production in the EP group (254mL/g VS) was higher than in the control group (35mL/g VS) because EP not only increased the buffering capacity of the system, but also increased hydrolytic acidification. More carbon source was converted to ethanol in the EP group than in the control group, and neutral ethanol could be converted continuously to acetic acid, which promoted the growth of Methanobacterium and Methanosarcina. As a result, the relative abundance of methane-producing bacteria was significantly higher than that of the control group. Kinetic modeling indicated that the EP group had a higher hydrolysis efficiency and shorter lag phase. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protective effect of [6]-gingerol on the ethanol-induced teratogenesis of cultured mouse embryos.

PubMed

Yon, Jung-Min; Baek, In-Jeoung; Lee, Se-Ra; Kim, Mi-Ra; Hong, Jin Tae; Yong, Hwanyul; Lee, Beom Jun; Yun, Young Won; Nam, Sang-Yoon

2012-01-01

Excessive ethanol consumption during pregnancy causes fetal alcohol syndrome. We investigated the effect of [6]-gingerol on ethanol-induced embryotoxicity using a whole embryo culture system. The morphological changes of embryos and the gene expression patterns of the antioxidant enzymes cytosolic glutathione peroxidase (cGPx), cytoplasmic Cu/Zn superoxide dismutase (SOD1), and Mn-SOD (SOD2), and SOD activity were examined in the cultured mouse embryos exposed to ethanol (5 μL/3 mL) and/or [6]-gingerol (1×10(-8) or 1×10(-7) μg/mL) for 2 days. In ethanol-exposed embryos, the standard morphological score of embryos was significantly decreased compared with those of the control (vehicle) group. However, cotreatment of embryos with [6]-gingerol and ethanol significantly improved all of the developmental parameters except crownrump length and head length, compared with those of the ethanol alone group. The mRNA expression levels of cGPx and SOD2, not SOD1, were decreased consistently, SOD activity were significantly decreased compared with the control group. However, the decreases in mRNA levels of antioxidant enzymes and SOD activity were significantly restored to the control levels by [6]-gingerol supplement. These results indicate that [6]-gingerol has a protective effect against ethanol-induced teratogenicity during mouse embryogenesis.

[A study on the expression of HSP70 in endothelial cells pretreated with ethanol and fluid shear stress].

PubMed

Yan, Hong-tao; Zhang, Yi; Liao, Ga; Zhang, Kui; Li, Bin; Wang, Ye; Liao, Zhi-gang

2006-07-01

To detect whether ethanol can affect the expression of HSP70 in endothelial cells under fluid shear stress. Ethanol at different concentrations was added to the culture medium of endothelial cells, EA. Hy926, which was treated statically or under 1Pa fluid shear stress. After the incubation of 1 h, 2 h, 4 h and 6 h, the expression of HSP70 was detected by immunohistochemical method(SP). In the control group, the expression of HSP70 was negative under static state, while it was positive under 1Pa fluid shear stress lasting 4 h even without ethanol. No statistic difference was found between the 50 mg/dL ethanol group and the control group with the same treatment time of fluid shear stress. HSP70 expression was found under static state with 150 mg/dL ethanol after 4 h or 300 mg/dL ethanol after 2 h respectively. The expression increased greatly under 1Pa fluid shear stress in the same ethanol concentrations. Medium to high ethanol concentration in coordination with fluid shear stress can strongly stimulates the expression of HSP70 by a kinetic mechanism of time-dependent.

Consistent, high-level ethanol consumption in pig-tailed macaques via a multiple-session, limited-intake, oral self-dosing procedure.

PubMed

Weed, Michael R; Wilcox, Kristin M; Ator, Nancy A; Hienz, Robert D

2008-06-01

Alcohol abuse is a major public health burden that can lead to many adverse health effects such as impaired hepatic, gastrointestinal, central nervous system and immune system function. Preclinical animal models of alcohol abuse allow for experimental control over variables often difficult to control in human clinical studies (e.g., ethanol exposure before or during the study, history of other drug use, access to medical care, nutritional status, etc). Nonhuman primate models in particular provide increased genetic, anatomic and physiologic similarity to humans, relative to rodent models. A small percentage of macaques will spontaneously consume large quantities of ethanol; however, most nonhuman primate models of "voluntary" ethanol intake produce relatively low daily ethanol intake in the majority of monkeys. To facilitate study of chronic exposure to high levels of ethanol intake, a macaque model has been developed that induces consistent, daily high-level ethanol consumption. This multiple-session procedure employed 4 drinking sessions per day, with sessions occurring once every 6 hours. The group average alcohol consumption was 4.6 g/kg/d (SEM 0.4), roughly twice the group average consumption of previous reports. Ethanol drinking sessions produced group mean blood ethanol levels of 95 mg/dl after 60 minutes, and fine motor control was impaired up to 90 minutes after a drinking session. This model of multiple-session, limited access, oral ethanol self-dosing produced consistent, high-level ethanol consumption with each session qualifying as a "binge" drinking session using the definition of "binge" provided by the NIAAA (>80 mg/dl/session). This model of ethanol drinking in macaques will be of great utility in the study of immunological, physiological and behavioral effects of ethanol in nonhuman primates.

Oxidative damage and histopathological changes in lung of rat chronically exposed to nicotine alone or associated to ethanol.

PubMed

Dhouib, H; Jallouli, M; Draief, M; Bouraoui, S; El-Fazâa, S

2015-12-01

Smoking is the most important preventable risk factor of chronic obstructive pulmonary disease and lung cancer. This study was designed to investigate oxidative damage and histopathological changes in lung tissue of rats chronically exposed to nicotine alone or supplemented with ethanol. Twenty-four male Wistar rats divided into three groups were used for the study. The nicotine group received nicotine (2.5mg/kg/day); the nicotine-ethanol group was given simultaneously same dose of nicotine plus ethanol (0.2g/kg/day), while the control group was administered only normal saline (1 ml/kg/day). The treatment was administered by subcutaneous injection once daily for a period of 18 weeks. Chronic nicotine administration alone or combined to ethanol caused a significant increase in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and catalase (CAT) activity in lung tissue compared to control rats suggesting an oxidative damage. However, these increases were mostly prominent in nicotine group. The histopathological examination of lung tissue of rats in both treated groups revealed many alterations in the pulmonary structures such as emphysema change (disappearance of the alveolar septa, increased irregularity and size of air sacs) and marked lymphocytic infiltration in perivascular and interstitial areas. However, the changes characterized in the nicotine group (pulmonary congestion, hemorrhage into alveoli and interstitial areas, edema) were more drastic than those observed in the nicotine-ethanol group, and they can be attributed to a significant degree of capillary endothelial permeability and microvascular leak. Conversely, the ethanol supplementation caused an appearance of fatty change and fibrosis in pulmonary tissue essentially due to a metabolism of ethanol. Finally, the lung damage illustrated in nicotine group was more severe than that observed in the nicotine-ethanol group. We conclude that the combined administration of nicotine and ethanol may moderate the effect of nicotine administered independently by counteractive interactions between these two drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Morphine decreases social interaction of adult male rats, while THC does not affect it.

PubMed

Šlamberová, R; Mikulecká, A; Macúchová, E; Hrebíčková, I; Ševčíková, M; Nohejlová, K; Pometlová, M

2016-12-22

The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.

The investigation of the prenatal and postnatal alcohol exposure-induced neurodegeneration in rat brain: protection by betaine and/or omega-3.

PubMed

Kusat Ol, Kevser; Kanbak, Güngör; Oğlakcı Ilhan, Ayşegül; Burukoglu, Dilek; Yücel, Ferruh

2016-03-01

We aim to study the effect of neurodegeneration on the brain of rat pups caused by prenatal and postnatal ethanol exposure with modified liquid diet to elucidate protective effects of betaine and omega-3 supplementation. When ethanol is consumed during prenatal and postnatal periods, it may result in fetal alcohol syndrome (FAS) in the offspring. Rats were divided into control, ethanol, ethanol + betaine, ethanol + omega-3, ethanol + omega-3 + betaine groups. The effect of betaine and omega-3 in response to ethanol-induced changes on the brain, by biochemical analyses cytochrome c, caspase-3, calpain, cathepsin B and L, DNA fragmentation, histological and morfometric methods were evaluated. Caspase-3, calpain, cathepsin B, and cytochrome c levels in ethanol group were significantly higher than control. Caspase-3, calpain levels were decreased in ethanol + betaine, ethanol + omega-3, and ethanol + omega-3 + betaine groups compared to ethanol group. Cathepsin B in ethanol + omega-3 + betaine group was decreased compared to ethanol, ethanol + betaine groups. Cathepsin L and DNA fragmentation were found not statistically significant. We found similar results in histological and morfometric parameters. We found that pre- and postnatal ethanol exposure is capable of triggering necrotic cell death in rat brains, omega-3, and betaine reduce neurodegeneration. Omega-3 and betaine may prove beneficial for neurodegeneration, particularly in preventing FAS.

[Antiurolithic Activity of the Ethanolic Extract of Ayacuchano Propolis in Rats].

PubMed

López-Cabanillas, Rita; Huayanay-Conde, Ronal; Gonzales, Cinthya; Maguiña, Mahli; Granados, Italo; Ccasani, Mila; Laguna, Astrid; León, Ernesto; Romero-Caballero, Nuria; Chacón, Jessenia

2017-01-01

To determine the antiurolytic activity of the ethanolic extract of Ayacuchan propolis in a preventive model of urolithiasis in rats. A total of 45 male Sprague-Dawley albino rats were studied. The antiurolithic effect was analyzed in five groups of six animals each: blank, control (treated with 1 mL of 5% ethylene glycol and 1 mL of 5% ammonium chloride), and three experimental groups (treated with the ethanol extract of propolis at a daily dose of 250, 350, and 500 mg/kg, respectively). The drugs were administered by orogastric cannulation for 16 days. The diuretic effect was evaluated in 15 rats distributed in five groups: blank, control (treated with furosemide at 20 mg/kg), and three experimental groups (treated with the ethanol extract of propolis at daily doses of 250, 350, and 500 mg/kg, respectively). Urinary pH, urinary density, and sedimentation of calcium oxalate were measured. The presence of kidney stones was evaluated by examination of hematoxylin-eosin-stained histopathological sections under polarized light. The ethanolic extract of Ayacuchan propolis caused significant changes in the levels of uric acid, serum lactate dehydrogenase, pH, and urinary density in the three dose groups. The results of histological analysis indicated a lower presence of calcium oxalate crystals in kidney tubular cells in the group treated with 250 mg/kg. The diuretic effect in the group treated with 250 mg/kg was higher than that in the control group. The ethanolic extract of Ayacuchan propolis demonstrated antiurolytic activity in a preventive rat model of urolithiasis.

Atrial and ventricular septal changes in ethanol vapour exposed chick embryos.

PubMed

Kamran, Kiran; Khan, Muhammad Yunus; Minhas, Liaqat Ali

2015-03-01

To study the effects of ethanol vapour exposure on development of atrial and ventricular septa of chick embryo. The experimental study was conducted at the College of Physicians and Surgeons, Islamabad, from 2006 to 2007. The experimental and control groups were further divided into three subgroups based on the day of sacrifice. The experimental group was exposed to ethanol vapours produced in a specially-designed vapour chamber and then compared with age-matched controls. There were 90 eggs in each of the two groups. The development of inter-ventricular septum completed at day 7 of development in chick embryo. Ethanol vapour exposure produced a small discontinuity at day 10 of development in a chick embryo which may be labelled as ventricular septal defect since ventricular development is completed by day 7. Interatrial septum formed till day 7 with small perforations which persisted till hatching. Ethanol vapour exposure may lead to ventricular septal defect.

Ginger extract mitigates ethanol-induced changes of alpha and beta - myosin heavy chain isoforms gene expression and oxidative stress in the heart of male wistar rats.

PubMed

Shirpoor, Alireza; Zerehpoosh, Mitra; Ansari, Mohammad Hasan Khadem; Kheradmand, Fatemeh; Rasmi, Yousef

2017-09-01

The association between ethanol consumption and heart abnormalities, such as chamber dilation, myocyte damage, ventricular hypertrophy, and hypertension is well known. However, underlying molecular mediators involved in ethanol-induced heart abnormalities remain elusive. The aim of this study was to investigate the effect of chronic ethanol exposure on alpha and beta - myosin heavy chain (MHC) isoforms gene expression transition and oxidative stress in rats' heart. It was also planned to find out whether ginger extract mitigated the abnormalities induced by ethanol in rats' heart. Male wistar rats were divided into three groups of eight animals as follows: Control, ethanol, and ginger extract treated ethanolic (GETE) groups. After six weeks of treatment, the results revealed a significant increase in the β-MHC gene expression, 8- OHdG amount, and NADPH oxidase level. Furthermore, a significant decrease in the ratio of α-MHC/β-MHC gene expression to the amount of paraoxonase enzyme in the ethanol group compared to the control group was found. The consumption of Ginger extract along with ethanol ameliorated the changes in MHC isoforms gene expression and reduced the elevated amount of 8-OHdG and NADPH oxidase. Moreover, compared to the consumption of ethanol alone, it increased the paraoxonase level significantly. These findings indicate that ethanol-induced heart abnormalities may in part be associated with MHC isoforms changes mediated by oxidative stress, and that these effects can be alleviated by using ginger extract as an antioxidant molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

Urine ethanol concentration and alcohol hangover severity.

PubMed

Van de Loo, Aurora; Mackus, Marlou; Korte-Bouws, Gerdien; Brookhuis, Karel; Garssen, Johan; Verster, Joris

2017-01-01

The aim of this study was to examine the relationship between urine ethanol concentration and alcohol hangover severity. N = 36 healthy social drinkers participated in a naturalistic study, comprising a hangover day and a control day. N = 18 of them have regular hangovers (the hangover group), while the other N = 18 claim to be hangover immune (hangover-immune group). On each test day at 9.30 am, urine samples were collected. Participants rated their overall hangover severity on a scale from 0 (absent) to 10 (extreme), as well as 18 individual hangover symptoms. Urine ethanol concentration was significantly higher on the hangover day when compared to the control day (p = 0.006). On the hangover day, urine ethanol concentration was significantly lower in the hangover-immune group when compared to the hangover group (p = 0.027). In the hangover-immune group, none of the correlations of urine ethanol concentration with individual hangover symptoms was significant. In contrast, in the hangover group, significant correlations were found with a variety of hangover symptoms, including nausea, concentration problems, sleepiness, weakness, apathy, sweating, stomach pain, thirst, heart racing, anxiety, and sleep problems. Urine ethanol levels are significantly associated with the presence and severity of several hangover symptoms.

The effect of ethanol vapour exposure on atrial and ventricular walls of chick embryos.

PubMed

Kamran, Kiran; Khan, Muhammad Yunus; Minhas, Liaqat Ali

2016-10-01

To study the effects of ethanol vapour exposure on atrial and ventricular walls of heart in chick embryo. The study design was experimental, conducted at Islamabad Centre of College of Physicians and Surgeons, Pakistan. One hundred and eighty chicken eggs were divided into two groups, experimental and control, of 90 eggs each. Each group was subdivided into three subgroups of 30 eggs each based on the day of sacrifice. Experimental group was exposed to ethanol vapours and then compared with age matched controls. The thickness of atrial and ventricular walls along with lengths of valvular cusps increased in hearts of day 7 and day 10 chick embryos in experimental group. There was thinning of walls and decreased length of valvular cusps in hearts of experimental chicks on hatching as compared to age matched controls. Ethanol vapour exposure during development causes cardiac and septal wall thickening during initial days of development followed by cardiac and septal wall thinning which is a classical picture of alcohol induced cardiomyopathies.

Changes in oral ethanol self-administration patterns resulting from ethanol concentration manipulations.

PubMed

Slawecki, C J; Samson, H H

1997-09-01

A variety of initiation procedures have been used to develop oral ethanol consumption. Using the sucrose-substitution procedure, oral self-administration of ethanol-water solutions with ethanol concentrations as high as 40% can be initiated in food- and fluid-sated rats. An important question for these models is the relationship between ethanol concentration and self-administration patterns after initiation. This study examined the differential patterns of ethanol self-administration maintained by a range of ethanol solutions (10 to 30%) over a 5-week period, compared with rats maintained on 10% ethanol for 5 weeks. In 43 male Long Evans rats, the sucrose-substitution procedure was used to initiate responding maintained by 10% ethanol on a Fixed Ratio 4 schedule of reinforcement. The ethanol concentration presented was then increased to 30% in stepwise fashion and then returned to 10% [Ethanol Concentration Manipulation (ECM) group, n = 32], or 10% ethanol was maintained as the reinforcer for 5 weeks [Control (Con) group, n = 11]. Significant increases in ethanol intake and decreases in responding were associated with increased ethanol concentration. Although no overall differences in total session responding were observed in either group between week 1 and week 5 (10E vs. 10E), examination of changes in initial low responders of the ECM group revealed significant increases in responding that were not observed in the initial low responders of the Con group. Significant increases in momentary response rates were observed on both the ECM and Con groups, independent of the ethanol concentration presented. Increases in response rate in the ECM group were the result of increases in initial low rate and high rate responders; however, the increased response rates in the Con group were the result of increases only in the initial low rate responders. These data suggest that the ECM procedure can aid in the initiation of ethanol self-administration and may be particularly useful in rats of heterogeneous stock.

Social opportunity and ethanol drinking in rats.

PubMed

Tomie, Arthur; Burger, Kelly M; Di Poce, Jason; Pohorecky, Larissa A

2004-11-01

Two experiments were designed to evaluate the effects of pairings of ethanol sipper conditioned stimulus (CS) with social opportunity unconditioned stimulus (US) on ethanol sipper CS-directed drinking in rats. In both experiments, rats were deprived of neither food nor water, and initiation of drinking of unsweetened 3% ethanol was evaluated, as were the effects of increasing the concentration of unsweetened ethanol (3-10%) across sessions. In Experiment 1, Group Paired (n=8) received 35 trials per session wherein the ethanol sipper CS was presented for 10 s immediately prior to 15 s of social opportunity US. All rats initiated sipper CS-directed drinking of 3% ethanol. Increasing the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8%, 10% (vol./vol.)] across sessions induced escalation of daily g/kg ethanol intake. To evaluate the hypothesis that the drinking in Group Paired was due to autoshaping, Experiment 2 included a pseudoconditioning control that received sipper CS and social opportunity US randomly with respect to one another. All rats in Group Paired (n=6) and in Group Random (n=6) initiated sipper CS-directed drinking of 3% ethanol and daily mean g/kg ethanol intake in the two groups was comparable. Also comparable was daily g/kg ethanol intake, which increased for both groups with the availability of higher concentrations of ethanol in the sipper CS, up to a maximum of approximately 0.8 g/kg ethanol intake of 10% ethanol. Results indicate that random presentations of ethanol sipper CS and social opportunity US induced reliable initiation and escalation of ethanol intake, and close temporally contiguous presentations of CS and US did not induce still additional ethanol intake. This may indicate that autoshaping CR performance is not induced by these procedures, or that high levels of ethanol intake induced by factors related to pseudoconditioning produces a ceiling effect. Implications for ethanol drinking in humans are discussed.

Effects of an ethanol-paired CS on responding for ethanol and food: Comparisons with a stimulus in a Truly-Random-Control group and to a food-paired CS on responding for food.

PubMed

Lamb, R J; Ginsburg, Brett C; Schindler, Charles W

2016-12-01

Motivational increases due to exposure to alcohol-paired Conditioned Stimuli (CS) are central to some accounts of alcoholism. However, few studies isolate a stimulus's function as a CS from its other potential functions. Pavlovian-Instrumental-Transfer (PIT) procedures isolate a stimulus's function as a CS from its other functions. Though there are several relevant studies using PIT, knowledge gaps exist. Particularly, it is not clear that an alcohol-paired CS will increase alcohol seeking compared to the same stimulus in a Truly-Random-Control group, nor whether such increases are specific to alcohol seeking. To address these knowledge gaps in Experiment 1, rats responded for ethanol (0.1 ml 8% w/v) under an RI 30-sec schedule, then the lever was removed and half the rats had ethanol delivered during occasional 120-sec light presentations, while the remainder had ethanol and the light presented under independent RT schedules. Later the lever was returned and the light was presented during responding in extinction (PIT test). Following this test, levers were again removed and the light was presented without ethanol (light extinction), following again by a PIT test. Responding in the two groups during light presentations did not differ in either PIT test. Experiment 2 repeated Experiment 1 using food instead of ethanol. In Experiment 2, responding during light presentations increased in the paired group. In Experiment 3, rats were trained on a concurrent FR schedule of food and ethanol delivery. Ethanol was delivered following 5 responses and the response requirement for food adjusted so that similar numbers of food and ethanol deliveries were obtained. Subsequently, rats underwent conditioning, control and testing procedures identical to those in Experiment 1. In Experiment 3, the ethanol-paired CS increased ethanol-responding, but not food-responding. These results are most easily interpreted as changes in responding resulting from CS-elicited behavior rather than motivational changes. This interpretation is more compatible with some descriptions of the role of an alcohol-paired CS in alcoholism than others. Copyright © 2016 Elsevier Inc. All rights reserved.

A possible role of a cerebral energy gene in alcoholism.

PubMed

Ribeiro, A F; Correia, D; Boerngen-Lacerda, R; Brunialti-Godard, A L

2012-02-17

We examined a possible relationship between genes responsible for energy metabolism of the brain and addictive behavior in an animal model. We used non-inbred, Swiss mice exposed to a three-bottle free-choice model [water, 5% (v/v) ethanol, and 10% (v/v) ethanol] over a 16-week period, consisting of four phases: acquisition, withdrawal, reexposure, and quinine-adulteration. The mice were then behaviorally classified into three groups: loss-of-control-drinker (preference for ethanol and high levels of consumption during all phases, N = 6), heavy-drinker (preference for ethanol and high levels of consumption during acquisition and reduction during quinine-adulteration, N = 7), and light-drinker (preference for water during all phases, N = 10). Another group only received tap water (ethanol-naive control mice, N = 9). Further analysis using quantitative real-time PCR showed that in mice behaviorally classified as loss-of-control-drinkers, there was a significant inverse correlation between transcript levels of the Hadh gene and those of other energy metabolism genes in the nucleus of the amygdala, suggesting that this pathway may contribute to ethanol consumption in these mice. We conclude that cerebral energy metabolism is involved with ethanol addiction, meriting further study.

Lack of relation between drug-seeking behavior in an addiction model and the expression of behavioral sensitization in response to ethanol challenge in mice.

PubMed

Ribeiro, A F; Pigatto, G; Goeldner, F O; Lopes, J F; de Lacerda, R B

2008-01-01

Drug-induced sensitization has been associated with enhanced self-administration and may contribute to addiction. The possible association between sensitization and voluntary ethanol consumption using an addiction model was investigated. Mice (n = 60) were individually housed with ad libitum access to food and had free choice between ethanol (5% and 10%) and water in a four-phase paradigm: free choice (12 weeks), withdrawal (2 weeks), re-exposure (2 weeks), and quinine-adulteration (2 weeks). Control mice (n = 10) had access to water. Mice were characterized as addicted (n = 10, ethanol preference without reducing intake with adulterated ethanol), heavy (n = 22, ethanol preference but reduced intake with adulterated ethanol), and light (n = 21, water preference). Oral ethanol then was withdrawn, and 24 h later mice received a 2 g/kg ethanol (i.p.) challenge dose or saline, and ambulation was evaluated 10 min later. Half of the classified mice received daily 2 g/kg ethanol injections for 14 days, and ambulation was assessed 10 min after the last dose. Acute ethanol increased ambulation in all groups compared to the control group, and chronic ethanol induced sensitization, showing no difference among ethanol-treated mice. The data suggest that independent neural mechanisms are responsible for the development of addiction and sensitization.

Wound healing activity of Sida cordifolia Linn. in rats.

PubMed

Pawar, Rajesh S; Chaurasiya, Pradeep K; Rajak, Harish; Singour, Pradeep K; Toppo, Fedelic Ashish; Jain, Ankit

2013-01-01

The present study provides a scientific evaluation for the wound healing potential of ethanolic (EtOH) extract of Sida cordifolia Linn. (SCL) plant. Excision, incision and burn wounds were inflicted upon three groups of six rats each. Group I was assigned as control (ointment base). Group II was treated with 10% EtOH extract ointment. Group III was treated with standard silver sulfadiazine (0.01%) cream. The parameters observed were percentage of wound contraction, epithelialization period, hydroxyproline content, tensile strength including histopathological studies. It was noted that the effect produced by the ethanolic extract of SCL ointment showed significant (P < 0.01) healing in all wound models when compared with the control group. All parameters such as wound contraction, epithelialization period, hydroxyproline content, tensile strength and histopathological studies showed significant (P < 0.01) changes when compared with the control. The ethanolic extract ointment of SCL effectively stimulates wound contraction; increases tensile strength of excision, incision and burn wounds.

Effects of short-term prenatal alcohol exposure on maze, activity, and olfactory orientation performance in rats.

PubMed

Vorhees, C V; Fernandez, K

1986-01-01

Long-Evans rats were gavaged twice each day with 4 g/kg/day, of ethanol on days 10-14 of gestation. Ethanol and control offspring were reared by untreated surrogate dams to minimize possible postnatal maternal treatment influences. Ethanol-exposed offspring exhibited delayed olfactory orientation (discrimination) to home cage scent and delayed lower incisor eruption compared to pair-fed or ad lib fed controls. After weaning, the ethanol offspring exhibited increased open-field section entries, particularly of centrally located sections, and facilitated swimming performance in a water maze. Ethanol exposure significantly decreased weight gain and increased postnatal, but not prenatal, mortality in the progeny. The female ethanol offspring also showed delayed vaginal patency development. This was due to large delays in vaginal development in a small number of individuals in this group; no such lag was seen in any members of either control group. The data confirm that short-term prenatal alcohol exposure can produce many of the behavioral effects previously reported when alcohol is administered throughout most or all of pregnancy.

Neuroprotective Effect of Exogenous Melatonin on Dopaminergic Neurons of the Substantia Nigra in Ovariectomized Rats

PubMed Central

Mehraein, Fereshteh; Talebi, Reza; Jameie, Behnamedin; Joghataie, Mohammad Taghi; Madjd, Zahra

2011-01-01

Background: Melatonin has receptors in substantia nigra pars compacta (SNc) and regulates development of dopaminergic (DA) neurons. This study was undertaken to determine ability of melatonin to protect SNc dopaminergic neuron loss induced by estrogen deficiency in ovariectomized rats. Methods: Female rats were randomized into four groups of seven each: control, ethanol sham, ovariectomy (ovx) and ovx with melatonin (ovx + m). In ovx, ovaries were removed. Ovx + m group was intraperitoneally injected with melatonin for 10 days, while the ethanol sham group received only ethanol. All rats were perfused with 4% paraformaldehyde, midbrains removed, fixed and paraffin embedded, then processed for Nissl and tyrosine hydroxylase staining (IHC). Ten sections of SNc in Nissl and IHC staining were analyzed in each animal, Nissl stained and tyrosine hydroxylase (TH) immunoreactive cells were counted in five experimental groups randomly. Data was analyzed using SPSS by ANOVA and t-test. Differences were considered significant for P<0.05. Results: There was less cell number in ovx compared to control and ethanol sham groups significantly (P<0.001). The ovx + m group had more cells than the ovx group in the SNc significantly (P<0.001). Furthermore, there was significant decrease of TH positive cell number in the ovx group compared to control and ethanol sham groups (P<0.05). The number of TH immunoreactive cells was higher in ovx + m compared to the ovx group (P<0.05). Conclusion: These findings can be compared with human and used in clinical application for prevention of DA neuron death of SNc after ovariectomy. PMID:21725499

Deficits in the extinction of ethanol-seeking behavior following chronic intermittent ethanol exposure are attenuated with positive allosteric modulation of mGlu5.

PubMed

Gass, J T; McGonigal, J T; Chandler, L J

2017-02-01

Alcoholism is a chronic relapsing disorder characterized by periods of heavy alcohol consumption and unsuccessful attempts at abstinence. Relapse is one of the most problematic aspects in the treatment of alcoholism and is triggered by ethanol-associated cues. Extinction-based cue exposure therapies have proven ineffective in the treatment of alcoholism. However, positive allosteric modulation of mGlu5 with CDPPB enhances the extinction learning of alcohol-seeking behavior. The current study investigated the impact of chronic alcohol exposure on the extinction of ethanol-seeking behavior. Adult Wistar rats were trained to self-administer alcohol with a light/tone stimulus serving as the alcohol cue. After training, one group of rats was exposed to chronic intermittent ethanol (CIE) daily for a period of 2 weeks to induce ethanol dependence. Control rats were exposed to air for the same period of time. Both groups were then retrained to self-administer ethanol and subsequently tested for changes in extinction learning. CIE exposed rats consumed more ethanol compared to their pre-CIE levels and to control rats. During extinction training, CIE rats responded significantly more on the previously active lever and required more sessions to reach extinction criteria compared to control rats. Treatment with CDPPB facilitated extinction in control rats and attenuated the increased resistance to extinction in CIE-exposed rats. These results demonstrate that chronic ethanol exposure not only alters ethanol intake, but also the extinction of ethanol-seeking behaviors. The ability to attenuate deficits through modulation of mGlu5 provides a potential target for pharmacological manipulation that could ultimately reduce relapse in alcoholics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid

PubMed Central

A. Ketuly, Kamal; A. Hadi, A. Hamid; Golbabapour, Shahram; Hajrezaie, Maryam; Hassandarvish, Pouya; Ali, Hapipah Mohd; Majid, Nazia Abdul; Abdulla, Mahmood A.

2013-01-01

Background Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats. Methodology/Principal Finding Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. Conclusion/Significance The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent. PMID:23516624

Acute toxicity and gastroprotection studies with a newly synthesized steroid.

PubMed

Ketuly, Kamal A; Hadi, A Hamid A; Golbabapour, Shahram; Hajrezaie, Maryam; Hassandarvish, Pouya; Ali, Hapipah Mohd; Abdul Majid, Nazia; Abdulla, Mahmood A

2013-01-01

Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3'H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats. Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.

Effect of ethanol-wet bonding with hydrophobic adhesive on caries-affected dentine.

PubMed

Huang, Xueqing; Li, Li; Huang, Cui; Du, Xijin

2011-08-01

Frequently encountered in clinical practice, caries-affected dentine (CAD) is the most challenging bonding substrate. This study evaluated the effect of ethanol-wet bonding with hydrophobic adhesive to sound dentine and to CAD. In the control groups, prepared sound dentine and CAD were bonded with Adper Single Bond 2 using a traditional water-wet bonding technique. In the experimental groups, the specimens were treated as follows: Group 1, rinsed with stepwise ethanol dehydration; Group 2, immersion in 100% ethanol, three times, for 20 s each time; and Group 3, immersion in 100% ethanol for 20 s. Microtensile bond strength (μTBS) testing was used to evaluate the effects of the different protocols on bonding. The microhardness of debonded dentine surfaces was measured to ensure the presence of CAD. Interfacial nanoleakage was evaluated by field-emission scanning electron microscopy. Treatment significantly improved the μTBS in CAD in Groups 1 and 2, but had no effect on Group 3. Conversely, treatment significantly reduced the μTBS in sound dentine in Groups 2 and 3, but had no effect in Group 1. The presence of nanoleakage varied with the ethanol-wet protocol used. In conclusion, ethanol-wet bonding can potentially improve bond efficacy to CAD when an appropriate protocol is used. © 2011 Eur J Oral Sci.

Loss of control over the ethanol consumption: differential transcriptional regulation in prefrontal cortex.

PubMed

de Paiva Lima, Carolina; da Silva E Silva, Daniel Almeida; Damasceno, Samara; Ribeiro, Andrea Frozino; Rocha, Cristiane S; Berenguer de Matos, Alexandre H; Correia, Diego; Boerngen-Lacerda, Roseli; Brunialti Godard, Ana Lúcia

2017-09-01

Alcohol use disorder (AUD) is a complex multifactorial disease with heritability of ∼50% and corresponds to the state in which the body triggers a reinforcement or reward compulsive behavior due to ethanol consumption, even when faced with negative consequences. Although several studies have shown the impact of high ethanol intake on the prefrontal cortex (PFC) gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with relapsing. In this study, we used a chronic three-bottle free-choice mouse model to investigate the PFC transcriptome in three different groups of mice drinkers: 'Light drinkers' (preference for water throughout the experiment); 'Heavy drinkers' (preference for ethanol with a non-compulsive intake), and 'Inflexible drinkers' (preference for ethanol with a compulsive drinking component). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the PFC, a brain region critical for the development and maintenance of alcohol addiction. We found that the Camk2a gene showed a downregulated profile only in the Inflexible when compared to the Light drinkers group, the Camk2n1 and Pkp2 genes showed an upregulated profile only in the Inflexible drinkers when compared to the Control group, and the Gja1 gene showed an upregulated profile in the Light and Inflexible drinkers when compared to the Control group. These different transcription patterns have been associated to the presence of alcohol, in the Camk2n1 and Gja1 genes; to the amount of ethanol consumed, in the Camk2a gene; and to the loss of control in the alcohol consumption, in the Pkp2 gene. Here, we provide, for the first time, the potential involvement of the Pkp2 gene in the compulsivity and loss of control over the voluntary ethanol consumption.

Amelioration of cerebellar dysfunction in rats following postnatal ethanol exposure using low-intensity pulsed ultrasound.

PubMed

Bolbanabad, Hiva Mohammadi; Anvari, Enayat; Rezai, Mohammad Jafar; Moayeri, Ardashir; Kaffashian, Mohammad Reza

2017-04-01

The neonatal development stage of the cerebellum in rats is equivalent to a human foetus in the third trimester of pregnancy. In this stage, cell proliferation, migration, differentiation, and synaptogenesis occur. Clinical and experimental findings have shown that ethanol exposure during brain development causes a variety of disruptions to the brain, including neurogenesis depression, delayed neuronal migration, changes in neurotransmitter synthesis, and neuronal depletion.During postnatal cerebellar development, neurons are more vulnerable to the destructive effects of ethanol. The effects of low-intensity pulsed ultrasound (LIPUS) on the number of cells and thickness of the cell layers within the cerebellar cortex were examined during the first two postnatal weeks in rats following postnatal ethanol exposure. Postpartum rats were distributed randomly into six groups. Normal saline was injected intraperitoneally into control animals and ethanol (20%) was injected into the intervention groups for three consecutive days. Intervention groups received LIPUS at different frequencies (3 or 5MHz), after administration of ethanol. After transcardial perfusion, the rat's brain was removed, and a complete series of sagittal cerebellum sections were obtained by systematic random manner. Photomicrographs were made with Motic digital cameras and analysed using Nikon digital software. The numbers of granular cells decreased in ethanol-treated rats compared to the control group. LIPUS, administered at (3 or 5MHz), combined with ethanol administration resulted in a reduction of ethanol's effects. Using 5MHz LIPUS resulted in significantly higher numbers of granular cells in the internal layer compared to the control rats. Using 3 or 5MHz LIPUS alone resulted in a significant enhancement in the granular cells of the molecular layer. A significant reduction was seen in the thickness of the external granular layer in ethanol-treated rats. This study showed that exposure to LIPUS can affect the number of granular cells and thickness of the cell layer within the cerebellar cortex in neonatal rats. LIPUS also could attenuate ethanol toxicity effects on the cerebellum. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective effect of Allium neapolitanum Cyr. versus Allium sativum L. on acute ethanol-induced oxidative stress in rat liver.

PubMed

Nencini, Cristina; Franchi, Gian Gabriele; Cavallo, Federica; Micheli, Lucia

2010-04-01

This study investigated the protective effect of Allium neapolitanum Cyr., a spontaneous species of the Italian flora, compared with garlic (Allium sativum L.) on liver injury induced by ethanol in rats. Male albino Wistar rats were orally treated with fresh Allium homogenates (leaves or bulbs, 250 mg/kg) daily for 5 days, whereas controls received vehicle only. At the end of the experimental 5-day period, the animals received an acute ethanol dose (6 mL/kg, i.p.) 2 hours before the last Allium administration and were sacrificed 6 hours after ethanol administration. The activities of catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GR) and the levels of malondialdehyde (MDA), ascorbic acid (AA), and reduced (GSH) and oxidized glutathione in liver tissue were determined. Administration of both Allium species for 5 days (leaves or bulbs) led to no statistical variation of nonenzymatic parameters versus the control group; otherwise Allium treatment caused an increase of GSH and AA levels compared with the ethanol group and a diminution of MDA levels, showing in addition that A. neapolitanum bulb had the best protective effect. Regarding to enzymatic parameters, GR and CAT activities were enhanced significantly compared with the ethanol group, whereas SOD activity showed a trend different from other parameters estimated. However, the treatment with both Allium species followed by acute ethanol administration reestablished the nonenzymatic parameters similar to control values and enhanced the activities of the enzymes measured. These results suggest that fresh Allium homogenates (leaves or bulbs) possess antioxidant properties and provide protection against ethanol-induced liver injury.

Chronic social instability increases anxiety-like behavior and ethanol preference in male Long Evans rats.

PubMed

Roeckner, Alyssa R; Bowling, Alexandra; Butler, Tracy R

2017-05-01

Chronic stress during adolescence is related to increased prevalence of anxiety disorders and alcohol use disorders in humans. This phenotype has been consistently recapitulated in animal models with male subjects, but models using female subjects are fewer. The aim of these studies was to test the hypothesis that chronic social instability (CSI) during adolescence engenders increased anxiety-like behavior, increased corticosterone, and greater ethanol intake and/or preference than control groups in male and female rats. A chronic social instability (CSI) procedure was conducted in separate cohorts of female and male adolescent Long Evans rats. CSI included daily social isolation for 1h, and then pair housing with a novel cage mate for 23h until the next 1h isolation period from PND 30-46. Control groups included social stability (SS), chronic isolation (ISO), and acute social instability (aSI). At PND 49-50, anxiety-like behavior was assessed on the elevated plus maze, and on PND 51 tails bloods were obtained for determination of corticosterone (CORT) levels. This was followed by 4weeks of ethanol drinking in a home cage intermittent access ethanol drinking paradigm (PND 55-81 for males, PND 57-83 for females). Planned contrast testing showed that the male CSI group had greater anxiety-like behavior compared controls, but group differences were not apparent for CORT. CSI males had significantly higher levels of ethanol preference during drinking weeks 2-3 compared to all other groups and compared to SS and ISO groups in week 4. For the female cohort, we did not observe consistent group differences in anxiety-like behavior, CORT levels were unexpectedly lower in the ISO group only compared to the other groups, and group differences were not apparent for ethanol intake/preference. In conclusion, chronic stress during adolescence in the form of social instability increases anxiety-like behavior and ethanol preference in male rats, consistent with other models of chronic stress during adolescence. Conversely, and contrary to our hypothesis, female rats' anxiety-like behavior, CORT level, and ethanol intake/preference were not altered by CSI. New paradigms must continue to be explored for study of clinically relevant relationships in female preclinical models. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary fructose augments ethanol-induced liver pathology.

PubMed

Thomes, Paul G; Benbow, Jennifer H; Brandon-Warner, Elizabeth; Thompson, Kyle J; Jacobs, Carl; Donohue, Terrence M; Schrum, Laura W

2017-05-01

Certain dietary components when combined with alcohol exacerbate alcohol-induced liver injury (ALI). Here, we tested whether fructose, a major ingredient of the western diet, enhances the severity of ALI. We fed mice ethanol for 8 weeks in the following Lieber-DeCarli diets: (a) Regular (contains olive oil); (b) corn oil (contains corn oil); (c) fructose (contains fructose and olive oil) and (d) corn+fructose (contains fructose and corn oil). We compared indices of metabolic function and liver pathology among the different groups. Mice fed fructose-free and fructose-containing ethanol diets exhibited similar levels of blood alcohol, blood glucose and signs of disrupted hepatic insulin signaling. However, only mice given fructose-ethanol diets showed lower insulin levels than their respective controls. Compared with their respective pair-fed controls, all ethanol-fed mice exhibited elevated levels of serum ALT; the inflammatory cytokines TNF-α, MCP-1 and MIP-2; hepatic lipid peroxides and triglycerides. All the latter parameters were significantly higher in mice given fructose-ethanol diets than those fed fructose-free ethanol diets. Mice given fructose-free or fructose-containing ethanol diets each had higher levels of hepatic lipogenic enzymes than controls. However, the level of the lipogenic enzyme fatty acid synthase (FAS) was significantly higher in livers of mice given fructose control and fructose-ethanol diets than in all other groups. Our findings indicate that dietary fructose exacerbates ethanol-induced steatosis, oxidant stress, inflammation and liver injury, irrespective of the dietary fat source, to suggest that inclusion of fructose in or along with alcoholic beverages increases the risk of more severe ALI in heavy drinkers. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of chronic ethanol consumption on the response of parathyroid hormone to hypocalcemia in the pregnant rat.

PubMed

Duggal, Shalu; Simpson, Mary Elizabeth; Keiver, Kathy

2007-01-01

Chronic alcohol (ethanol) consumption during pregnancy results in maternal/fetal hypocalcemia, which may underlie some of ethanol's adverse effects on maternal and fetal bone, and fetal/neonatal health. Ethanol appears to alter the relationship between parathyroid hormone (PTH) and blood calcium (Ca) level, and PTH does not increase in response to ethanol-induced hypocalcemia. However, it is not known whether ethanol actually prevents PTH from responding, or whether the ability to regulate blood Ca is intact, but ethanol lowers the level of Ca maintained. The objective of this study was to determine whether chronic ethanol consumption impairs the ability of the pregnant female to increase PTH in response to acute hypocalcemia. Rats were fed isocaloric diets with ethanol (36% ethanol-derived calories, E group) or without ethanol [pair-fed (PF) and control (C) groups], before and throughout 21 days of gestation. On day 21 gestation, rats received an intraperitoneal injection of ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (300 or 500 mumol/kg body weight) or saline (saline group), or no injection (baseline group). Blood was collected from the baseline group, and at 30 or 60 minutes postinjection (saline and EGTA groups), and analyzed for ionized Ca (iCa), pH, and PTH. Consistent with previous studies, ethanol consumption decreased blood iCa levels at baseline, but PTH levels did not differ among groups. Administration of EGTA significantly decreased blood iCa levels by 30 minutes, but ethanol did not prevent PTH from increasing in response to the hypocalcemia. In all diet groups, PTH levels were significantly increased by 30 minutes. Ethanol did, however, appear to decrease the maximum PTH level achievable in blood. These data suggest that chronic ethanol consumption does not impair the ability of the pregnant rat to raise serum PTH levels in response to acute hypocalcemia, but ethanol's effect on maximal PTH secretion could impair the ability of the pregnant female to sustain high PTH levels in response to chronic hypocalcemia.

Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves postnatal survival after prenatal ethanol exposure in mice.

PubMed

Summers, Brooke L; Rofe, Allan M; Coyle, Peter

2009-04-01

We have previously demonstrated that ethanol teratogenicity is associated with metallothionein-induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol-related dysmorphology. Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn-supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60. Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn-supplemented fetuses was not different from saline-treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre- or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un-supplemented groups. These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.

Pregnancy outcomes and ethanol cook stove intervention: A randomized-controlled trial in Ibadan, Nigeria.

PubMed

Alexander, Donee A; Northcross, Amanda; Karrison, Theodore; Morhasson-Bello, Oludare; Wilson, Nathaniel; Atalabi, Omolola M; Dutta, Anindita; Adu, Damilola; Ibigbami, Tope; Olamijulo, John; Adepoju, Dayo; Ojengbede, Oladosu; Olopade, Christopher O

2018-02-01

Household air pollution (HAP) exposure has been linked to adverse pregnancy outcomes. A randomized controlled trial was undertaken in Ibadan, Nigeria to determine the impact of cooking with ethanol on pregnancy outcomes. Three-hundred-twenty-four pregnant women were randomized to either the control (continued cooking using kerosene/firewood stove, n=162) or intervention group (received ethanol stove, n=162). Primary outcome variables were birthweight, preterm delivery, intrauterine growth restriction (IUGR), and occurrence of miscarriage/stillbirth. Mean birthweights for ethanol and controls were 3076 and 2988g, respectively; the difference, 88g, (95% confidence interval: -18g to 194g), was not statistically significant (p=0.10). After adjusting for covariates, the difference reached significance (p=0.020). Rates of preterm delivery were 6.7% (ethanol) and 11.0% (control), (p=0.22). Number of miscarriages was 1(ethanol) vs. 4 (control) and stillbirths was 3 (ethanol) vs. 7 (control) (both non-significant). Average gestational age at delivery was significantly (p=0.015) higher in ethanol-users (39.2weeks) compared to controls (38.2weeks). Perinatal mortality (stillbirths and neonatal deaths) was twice as high in controls compared to ethanol-users (7.9% vs. 3.9%; p=0.045, after adjustment for covariates). We did not detect significant differences in exposure levels between the two treatment arms, perhaps due to large seasonal effects and high ambient air pollution levels. Transition from traditional biomass/kerosene fuel to ethanol reduced adverse pregnancy outcomes. However, the difference in birthweight was statistically significant only after covariate adjustment and the other significant differences were in tertiary endpoints. Our results are suggestive of a beneficial effect of ethanol use. Larger trials are required to validate these findings. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol intake in rats.

PubMed

Sukul, N C; Ghosh, S; Sinhababu, S P; Sukul, A

2001-04-01

To see whether Strychnos nux-vomica extract (mother tincture [MT]), its potency Nux 30c, and its principal alkaloid, strychnine, could reduce voluntary ethanol intake in rats. To analyze the solution structure of Nux MT, Nux 30c, 90% ethanol, and ethanol 30c by means of electronic (ES) and nuclear nuclear magnetic resonance (NMR) spectra. Potentially alcoholic rats were first given 20% ethanol and then kept on a two-choice bottle, one with 20% ethanol and another with tap water. These rats were given the following oral treatments for 15 days: group 1, control; group 2, strychnine at 0.36 mg/kg per day; group 3, ethanolic extract of S. nux-vomica seeds (Nux MT) at 3.6 mg/kg per day; and group 4, Nux 30c at 0.05 mL/d per rat. Nux 30c was prepared by successive dilution of Nux MT and 90% ethanol (1:100) and sonication at 20 kHz for 30 seconds in 30 steps. Both Nux MT and Nux 30c significantly reduced ethanol intake and increased water intake in rats. ES of two dilutions of Nux MT and Nux 30c showed intersections at more than one point suggesting existence of molecular complexes. ES of Nux MT in CCl4 showed a red shift when 90% ethanol was added indicating molecular complexation and charge transfer interaction between ethanol and Nux compounds. NMR spectra of Nux MT, 90% ethanol, ethanol 30c, and Nux 30c indicated a change in solution structure of the medium (90% ethanol) of Nux 30c. Nux MT and Nux 30c could reduce ethanol intake in rats. The altered solution structure of Nux 30c is thought to mimic Nux MT and produce ethanol aversion in rats.

Wound healing activity of Sida cordifolia Linn. in rats

PubMed Central

Pawar, Rajesh S.; Chaurasiya, Pradeep K.; Rajak, Harish; Singour, Pradeep K.; Toppo, Fedelic Ashish; Jain, Ankit

2013-01-01

Introduction: The present study provides a scientific evaluation for the wound healing potential of ethanolic (EtOH) extract of Sida cordifolia Linn. (SCL) plant. Materials and Methods: Excision, incision and burn wounds were inflicted upon three groups of six rats each. Group I was assigned as control (ointment base). Group II was treated with 10% EtOH extract ointment. Group III was treated with standard silver sulfadiazine (0.01%) cream. The parameters observed were percentage of wound contraction, epithelialization period, hydroxyproline content, tensile strength including histopathological studies. Result: It was noted that the effect produced by the ethanolic extract of SCL ointment showed significant (P < 0.01) healing in all wound models when compared with the control group. All parameters such as wound contraction, epithelialization period, hydroxyproline content, tensile strength and histopathological studies showed significant (P < 0.01) changes when compared with the control. Conclusion: The ethanolic extract ointment of SCL effectively stimulates wound contraction; increases tensile strength of excision, incision and burn wounds. PMID:24130382

Hepatoprotective and nephroprotective effects of sardinelle (Sardinella aurita) protein hydrolysate against ethanol-induced oxidative stress in rats.

PubMed

Kamoun, Zeineb; Kamoun, Alya Sellami; Bougatef, Ali; Kharrat, Rim Marrakchi; Youssfi, Houssem; Boudawara, Tahia; Chakroun, Mouna; Nasri, Moncef; Zeghal, Najiba

2017-01-01

Ethanol consumption-induced oxidative stress that is a major etiological factor has been proven to play important roles in organs' injury. In the present study, we investigated the protective effect of fish protein hydrolysate prepared from the heads and viscera of sardinelle (Sardinella aurita) (SPH) against the toxicity of ethanol on the liver and kidney of adult male rats. Animals were divided into four groups of six animals each: group C served as control, group Eth received 30 % ethanol solution at the dose of 3 g/kg body weight, group SPH received only 7.27 mg of SPH/kg body weight, and group Eth-SPH received ethanol and SPH simultaneously at the doses of 30 % and 7.27 mg/kg body weight, respectively. All groups were treated by gavage way for 15 days. Ethanol treatment decreased the defense enzymatic system including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), which increased after the co-administration of SPH. Malondialdehyde (MDA) and toxicity biomarker levels such as aspartate transaminase (AST) and alanine transaminase (ALT) and alcaline phosphatase (ALP) and gamma-glutamyl transaminase (GGT) activities were enhanced after chronic ethanol treatment and reduced by co-treatment with SPH. The histological examination of the liver and kidney confirmed biochemical changes in ethanol-treated rats and demonstrated the protective role of SPH.

Chronic and intermittent exposure to alcohol vapors: a new model of alcohol-induced osteopenia in the rat.

PubMed

Maurel, Delphine B; Jaffré, Christelle; O'Brien, Emmanuelle Simon; Tournier, Carine C; Houchi, Hakim; Benhamou, Claude-Laurent; Naassila, Mickael

2013-01-01

Different models are used to study the effects of chronic alcohol consumption on bone tissue in the rat. However, the current models take several months to show indices of osteopenia as observed in chronic drinkers. Numerous studies have supported that chronic and intermittent exposure to ethanol vapors has predictive validity as a model of alcohol dependence in humans. However, this model has never been applied to bone research to study its effects on the parameters that define osteopenia. This was the goal of this study in the rat. Male Wistar rats were exposed to ethanol vapor inhalation (n = 6) or air (controls, n = 6). Animals were exposed to chronic (11 weeks) and intermittent (14 hours a day) ethanol vapor reaching stable blood alcohol levels (BALs; 150 to 250 mg/dl) at the end of the third week of inhalation. After the sacrifice, right and left femur and tibia were dissected free of fat and connective tissue and bone mineral density (BMD) was assessed by dual X-ray absorptiometry. The microarchitecture of the femur was studied using microcomputed tomography. The BMD of the left and right femurs and the left tibia was lower in the ethanol group compared with the control group. The bone volume fraction (BV/TV) and the bone surface density (BS/TV) were lower in the ethanol group compared with control animals. The trabecular number (Tb.N) was lower in the ethanol group while the trabecular spacing was higher. The decrease in the BMD, BV/TV, and Tb.N is in the same range as what is observed in human drinkers and what is reported with other animal alcohol models (Lieber-DeCarli liquid diet, ethanol in the tap water). Therefore, this model could be useful to study the effects of chronic alcohol consumption in the bone research field and has the advantage of controlling easily targeted BALs. Copyright © 2012 by the Research Society on Alcoholism.

The effect of Ipomoea reptans poir ethanolic extract on the histopathological parameters of pancreas in streptozotocin-induced diabetic rats

NASA Astrophysics Data System (ADS)

Hayati, Farida; Widyarini, Sitarina; Lanova, Lulung; Wijayanti, Marsih

2017-03-01

The aim of this study was to investigate the effect of ethanolic extract of Ipomoea reptans Poir in male Wistar rats on the histopathological parameters of the pancreas. The rats (N=30) were divided into six groups, each consisting of five rats. The treatment groups were divided into: group I as the normal group fed ad libitum during the research, group II as the positive control administered glibenclamide 0.09 mg/200g BW, group III as the negative control given aquadest, and group IV to VI given ethanolic extract of Ipomoea reptans Poir as much as 200 mg/KgBW, 400 mg/KgBW and 600 mg/KgBW respectively. The study of antidiabetic effect was undertaken by oral administration for 21 days. On the 21st day, all the rats were dissected to prepare histopathological preparates through Gomori's chrome alum hematoxylin-phloxine staining method. The histopathological study showed that the ethanol extract of Ipomoea reptans Poir at a dose of 200 mg/KgBW and 400mg/KgBW had an antidiabetic activity through protection of pancreatic β-cell from damage in male Wistar rats induced by streptozotocin.

Effect of subchronic administration of nutmeg (Myristica fragrans Houtt) ethanolic extract to hematological parameters in rat

NASA Astrophysics Data System (ADS)

Bachri, M. S.; Yuliani, S.; Sari, A. K.

2017-11-01

Nutmeg is dried kernel of broadly ovoid seed of Myristica fragrans Houtt. It has been mentioned in ethnomedical literature as aphrodisiac, stomachic, carminative, tonic, and nervous stimulant. In order to establish the safety of nutmeg, the effect of the repeated administration of nutmeg is needed. The study was aimed to determine the toxic effect of subchronic administration of nutmeg ethanolic extract to hematological parameters in rat. A total of 28 male adult Wistar rats divided into 4 groups. Group I as control was given by 0.5% CMC-suspension, group II, III, and IV were given by 50, 100, and 200 mg/kg bw, respectively, of nutmeg ethanolic extract. The treatments were administered daily for 31 days. On day 31 bloods were taken from orbital sinus. The hematological parameter consisted of the numbers of erythrocyte and leukocyte as well as hemoglobin and total protein levels were measured. The data were statistically analyzed by one way Anova followed by LSD test. All of observed hematological parameters in rats showed that there were no significant difference between the nutmeg ethanolic extract treated groups and control group. The result indicated that the subchronic administration of 50, 100, and 200 mg/kg bw of nutmeg ethanolic extract did not cause the change of hematological parameters in rat.

[Influence of carbodiimide-ethanol solution surface treatment on dentin microtensile bond strength].

PubMed

Zhang, Yi; Liu, Yu-hua; Zhou, Yong-sheng; Chung, Kwok-hung

2015-10-18

To evaluate the microtensile bond strength changes and patterns of fractures of the bonding interface after dentine surface treatment with carbodiimide-ethanol solution. 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) dissolved in ethanol was diluted into different concentrations of 2, 1, 0.3, 0.1 and 0.01 mol/L EDC-ethanol solutions. Twenty-eight caries-free extracted human third molars were ground metallurgically to prepare flat occlusal mid-coronal dentin surfaces and etched with 35% (mass fraction) phosphoric acid gel. Then they were treated with EDC-ethanol solution for 60 s before the bonding procedure and randomly divided into five experimental groups corresponding to the tested EDC-ethanol concentrations. The ethanol treated and no pre-treated surfaces were used as controls. Single Bond 2 adhesive was applied and resin composite disk was stacked on the treated dentine surface. The teeth with resin composite disks were stored in water at room temperature for 24 h and then sectioned longitudinally to produce stick specimens for microtensile bond strength test. Fracture patterns were observed with a stereomicroscope. The dentin surfaces pre-treated with 2 mol/L [(22.17±13.31) MPa] and 1 mol/L [(45.31±17.80) MPa] EDC-ethanol solutions resulted in statistically significant lower bond strength value (P<0.05). Increasing numbers of fracture pattern at the resin-dentin interface were also found in this two groups with percentages of 81.2% and 41.3% respectively. No significant difference was observed in the groups with 0.3, 0.1, 0.01 mol/L EDC surface treatment (P>0.05). No significant difference of immediate bond strengths was found in the 0.3, 0.1, 0.01 mol/L groups compared with the control group. EDC-ethanol solution surface treatment with concentrations of 2 mol/L and 1 mol/L resulted in decreasing of the bonding strength.

Cognitive enhancing of pineapple extract and juice in scopolamine-induced amnesia in mice

PubMed Central

Momtazi-borojeni, Amir Abbas; Sadeghi-Aliabadi, Hojjat; Rabbani, Mohammed; Ghannadi, Alireza; Abdollahi, Elham

2017-01-01

The objective of the present study was to evaluate the cognitive enhancing of pineapple juice and ethanolic extract in scopolamine-induced cognitive deficit mice. The ethanolic extract of pineapple (Ananas comosus (L.) Merr.) was prepared by maceration method and its juice was obtained by a homogenizer. Object recognition task was used to evaluate the mice memory. Exploration time in the first and second trial was recorded. The differences in exploration time between a familiar and a novel object in the second trial were taken as a memory index. Animals were randomly assigned into 15 groups of 6 each including: control group (normal saline + vehicle), positive control group (scopolamine + rivastigmine), seven experimental groups (received scopolamine alone or scopolamine + ethanolic extract of pineapple in different doses), six other experimental groups were treated by ethanolic extract or juice of pineapple in different doses. Scopolamine (100 μL, 1 mg/kg, i.p.) and pineapple juice or extract (50, 75 and 100 mg/kg, i.p.) were administered 40 and 30 min before starting the second trial in the experimental groups. Object discrimination was impaired after scopolamine administration. Results showed that juice and ethanolic extract of pineapple significantly restored object recognition ability in mice treated with scopolamine. These finding suggested that pineapple had a protective role against scopolamine-induced amnesia, indicating its ability in management of cognitive disorders. PMID:28626484

Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure.

PubMed

Wellmann, Kristen A; George, Finney; Brnouti, Fares; Mooney, Sandra M

2015-06-01

Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10 mg/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol's damaging effects. Copyright © 2015 Elsevier B.V. All rights reserved.

Overexpression of NGF ameliorates ethanol neurotoxicity in the developing cerebellum.

PubMed

Heaton, M B; Mitchell, J J; Paiva, M

2000-11-05

Transgenic mice overexpressing NGF in the central nervous system under the control of the glial fibrillary acidic protein (GFAP) promoter were exposed to ethanol via vapor inhalation on postnatal days 4 and 5 (P4-5), the period of maximal cerebellar Purkinje cell sensitivity to ethanol. Wild-type controls were exposed in a similar manner. There were no differences in body weight or size following these procedures, but the transgenic brain weights at this age were significantly greater than wild-type controls. In the wild-type animals, a significant 33.3% ethanol-mediated loss of Purkinje cells in lobule I was detected via unbiased three-dimensional stereological counting on P5. In the GFAP-NGF transgenic animals, however, the 17.6% difference in Purkinje cell number in control and ethanol-exposed animals was not significant. There was a similar difference in Purkinje cell density in both groups, which did reach statistical significance (-32.7% in wild-type ethanol-treated animals, -17% in transgenic ethanol-exposed animals). These results suggest that endogenous overexpression of neurotrophic factors, which have previously been shown to protect against ethanol neurotoxicity in culture, can serve a similar protective function in the intact animal. Copyright 2000 John Wiley & Sons, Inc.

Calorie restriction inhibits relapse behaviour and preference for alcohol within a two-bottle free choice paradigm in the alcohol preferring (iP) rat.

PubMed

Guccione, Lisa; Djouma, Elvan; Penman, Jim; Paolini, Antonio G

2013-02-17

Among its many beneficial effects, calorie restriction (CR) has also been found to reduce anxiety related behavior in the rodent. With heightened levels of stress and anxiety implicated as a key precipitating factor of relapse and alcohol addiction, it was found that a 25% CR in addition to inducing anxiolytic effects also had the capacity to reduce intake of alcohol and inhibit relapse within a model of operant self-administration. The aim of this study was to investigate if a 25% CR would also display similar effects in a two-bottle free choice paradigm, whereby 24 h ad libitum access to both 10% ethanol and water is provided. All animals were initially tested on the elevated plus maze (EPM) and open field test prior to commencing the two-bottle free choice paradigm. Differences between control and CR25% animals demonstrated the anxiolytic effects of CR, with the CR25% group displaying greater percentage of open arm/total arm duration and open arm/total arm entries in the EPM. During the acquisition phase of the two-bottle free choice paradigm, CR25% animals showed a reduced intake of 10% ethanol in ml/kg, in comparison to the control group. Whilst control animals displayed a strong preference for 10% ethanol, the CR25% group consumed both 10% ethanol and water equally with no differences found in total fluid intake between groups. Similarly this was also the case following forced deprivation. In addition to reduced intake and lack of preference for 10% ethanol, CR 25% animals unlike controls failed to display a typical alcohol deprivation effect following abstinence. Taken collectively the results of this study suggest that CR may act as a protective factor against addiction and relapse in the alcohol preferring (iP) rat. In addition, given CR25% animals did not display a preference for 10% ethanol, results also suggest that CR may be altering the hedonic impact of ethanol within this group. Copyright © 2012 Elsevier Inc. All rights reserved.

Fomepizole versus ethanol in the treatment of acute methanol poisoning: Comparison of clinical effectiveness in a mass poisoning outbreak.

PubMed

Zakharov, Sergey; Pelclova, Daniela; Navratil, Tomas; Belacek, Jaromir; Komarc, Martin; Eddleston, Michael; Hovda, Knut Erik

2015-01-01

Mass or cluster methanol poisonings are frequently reported from around the world. The comparative effectiveness of ethanol and fomepizole as antidotes for methanol poisoning is unknown due to the difficulty of performing a randomized controlled trial. During an outbreak of mass poisonings in the Czech Republic in 2012-2014, we compared the effects of antidotes on the frequency of health sequelae and mortality. The study was designed as a cross-sectional case series and quasi-case-control study. Patients with a diagnosis of methanol poisoning on admission to hospitals were identified for the study. Diagnosis was established when (i) a history of recent ingestion of illicit spirits was available and serum methanol was higher than 6.2 mmol/L (20 mg/dL), or (ii) there was a history/clinical suspicion of methanol poisoning, and serum methanol was above the limit of detection with at least two of the following: pH < 7.3, serum bicarbonate < 20 mmol/L, and anion gap or AG ≥ 20 mmol/L. Fomepizole was given as a bolus dose of 15 mg/kg i.v. diluted in isotonic saline, followed by 10 mg/kg every 12 h (every 4 h during hemodialysis); ethanol was administered both intravenously as a 10% solution in 5% glucose, and per os in boluses of 20% solution. Multivariate regression was applied to determine the effect of antidote on outcome. Additionally, for a retrospective quasi-case-control study, a control group of patients treated with ethanol, matched carefully on severity of poisoning and other key parameters, was selected. Data were obtained from 100 hospitalized patients with confirmed poisoning: 25 patients treated with fomepizole were compared with 68 patients receiving ethanol (seven patients did not receive any antidote). More severely acidotic (p < 0.001) and late-presenting (>12 h; p = 0.028) patients received fomepizole more often than ethanol, as reflected in the higher number of fomepizole-treated patients being intubated (p = 0.009). No association was found between the type of antidote and the survival in either the case series (p = 0.205) or the quasi-control groups (p = 0.705) in which patients were very closely matched to minimize confounding by allocation. In the multivariate analysis, positive serum ethanol (odds ratio [OR], 10.8; 95% confidence interval [CI], 2.9-39.9) and arterial blood pH (OR, 3.7; 95% CI, 1.3-10.5) on admission were the only independent variables for the survival. The median intensive care unit length of stay was 6 (range, 2-22) days in the fomepizole group and 4 (range, 1-33) days in the ethanol group (p = 0.131). There were no differences in the use of elimination techniques between the two groups (neither in the full material (n = 100), nor the case-control groups (n = 50)). This study on antidotes for methanol poisoning did not show any evidence of different clinical effectiveness. Although ethanol is generally associated with a higher incidence of complications, this study suggests that both antidotes are similarly effective and that ethanol should not be avoided on grounds of effectiveness.

Variable effects of chronic intermittent ethanol exposure on ethanol drinking in a genetically diverse mouse cohort.

PubMed

Lopez, Marcelo F; Miles, Michael F; Williams, Robert W; Becker, Howard C

2017-02-01

The BXD family of mice were generated by crossing and inbreeding ethanol-preferring C57BL/6J and ethanol-avoiding DBA/2J strains that differ greatly in genome sequence and other behaviors. This study evaluated variations in the level of voluntary ethanol intake in a cohort of 42 BXD strains and both progenitor strains using a model of alcohol dependence and relapse drinking. A total of 119 BXDs (85 males, 34 females) (n ∼ 4 per genotype; 1/genotype/sex/group) were evaluated along with males from both progenitor strains (n = 14-15/genotype). Mice were evaluated for intake using limited access (2 h/day) 2-bottle (15% v/v ethanol vs. water) model for 6 weeks (baseline intake). Each animal received 4 weekly cycles of chronic intermittent ethanol (CIE) vapor exposure (CIE group) or air control exposure (CTL group) (16 h/day × 4 days) interleaved by 5-day drinking test cycles. Blood ethanol concentrations (BEC) ranged from 150 to 300 mg/dl across genotypes. Baseline intake varied greatly among cases-from ∼0.8 to ∼2.9 g/kg. As expected, CIE exposure induced a significant increase in ethanol drinking in C57BL/6J relative to baseline as well as air controls that remained relatively stable over the four test cycles. In contrast, DBA/2J cases did not show a significant increase in consumption. Heritability of variation in baseline consumption, calculated from C57BL/6J and DBA/2J strains is about 54% but this increases following treatment to 60-80%. As expected from the marked difference between progenitors, ethanol intake and level of escalation varied greatly among BXDs after exposure (∼-1.3 to 2.6 g/kg). Interestingly, the magnitude and direction of changes in ethanol intake did not relate to BEC values of the preceding CIE exposure cycle. Overall, these data indicate significant variation in consumption and even escalation, much of it under genetic control, following repeated CIE treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Variable Effects of Chronic Intermittent Ethanol Exposure on Ethanol Drinking in a Genetically Diverse Mouse Cohort

PubMed Central

Lopez, Marcelo F.; Miles, Michael F.; Williams, Robert W.; Becker, Howard C.

2016-01-01

The BXD family of mice were generated by crossing and inbreeding ethanol-preferring C57BL/6J and ethanol-avoiding DBA/2J strains that differ greatly in genome sequence and other behaviors. This study evaluated variations in the level of voluntary ethanol intake in a cohort of 42 BXD strains and both progenitor strains using a model of alcohol dependence and relapse drinking. A total of 119 BXDs (85 males, 34 females) (n ~ 4 per genotype; 1/genotype/sex/group) were evaluated along with males from both progenitor strains (n = 14–15/genotype). Mice were evaluated for intake using limited access (2 hr/day) 2-bottle (15% v/v ethanol vs. water) model for 6 weeks (baseline intake). Each animal received 4 weekly cycles of chronic intermittent ethanol (CIE) vapor exposure (CIE group) or air control exposure (CTL group) (16 hr/day × 4 days) interleaved by 5-day drinking test cycles. Blood ethanol concentrations (BEC) ranged from 150–300 mg/dl across genotypes. Baseline intake varied greatly among cases—from ~0.8 to ~2.9 g/kg. As expected, CIE exposure induced a significant increase in ethanol drinking in C57BL/6J relative to baseline as well as air controls that remained relatively stable over the four test cycles. In contrast, DBA/2J cases did not show a significant increase in consumption. Heritability of variation in baseline consumption, calculated from C57BL/6J and DBA/2J strains is about 54% but this increases following treatment to 60–80%. As expected from the marked difference between progenitors, ethanol intake and level of escalation varied greatly among BXDs after exposure (~-1.3 to ~2.6 g/kg). Interestingly, the magnitude and direction of changes in ethanol intake did not relate to BEC values of the preceding CIE exposure cycle. Overall, these data indicate significant variation in consumption and even escalation, much of it under genetic control, following repeated CIE treatment. PMID:27793543

Effect of chlorhexidine and ethanol on the durability of the adhesion of the fiber post relined with resin composite to the root canal.

PubMed

Cecchin, Doglas; de Almeida, José Flávio Affonso; Gomes, Brenda P F A; Zaia, Alexandre Augusto; Ferraz, Caio Cesar Randi

2011-05-01

The aim of this study was to investigate the effects of pretreatment of gel chlorhexidine and ethanol on the bond strength and durability of the adhesion of the fiber post relined with resin composite to the root dentin. Sixty bovine incisor roots were divided into four groups: irrigation with physiologic solution (control), 5 minutes with chlorhexidine, 1 minute with ethanol, and 5 minutes with chlorhexidine followed by 1 minute with ethanol. Fiber posts relined with resin composite were cemented with RelyX ARC (3M ESPE, St Paul, MN) and a self-etching adhesive system Clearfil SE Bond (Kuraray, Kurashiki, Japan). Each group was randomly divided into three subgroups: 24 hours of water storage, 12 months of water storage, and 12 months of oil storage. All roots were sectioned transversely in the coronal, middle, and apical regions, producing 1-mm thick slices, and the push-out test was performed. Statistical analysis was performed using analysis of variance and the Tukey test for post hoc comparisons (α = 0.05). Immediate groups showed similar bond strength values with or without chlorhexidine and/or ethanol pretreatment (P > .05). A significant decrease in the bond strength in the control group was observed after 12 months of storage in water and oil (P < .05). The use of chlorhexidine- and/or ethanol-preserved bond strength in the groups stored in water and oil for 12 months (P < .05). Chlorhexidine and/or ethanol pretreatment were capable of preserving the bond strength of the fiber post relined with resin composite to root dentin for 12 months. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Influence of rearing conditions on voluntary ethanol intake and response to stress in rats.

PubMed

Rockman, G E; Hall, A M; Markert, L E; Glavin, G B

1988-03-01

The effects of exposure to four environmental rearing conditions on subsequent voluntary ethanol intake and response to immobilization stress were examined. Male weanling rats were reared in an enriched environment, with a female partner, with a male partner, or individually, for 90 days. At 111 days of age, voluntary consumption of ethanol in increasing concentrations (3 to 9%, v/v) was assessed. Following the ethanol-exposure period, rats were randomly divided into stressed and nonstressed groups and exposed to 3 h of immobilization. Results indicated that the enriched animals consumed greater amounts of ethanol as compared to all other groups, suggesting that the enriched environment and not handling, housing conditions, or the presence of another male or female is responsible for the observed increase in ethanol drinking behavior. Ulcer data indicated that among environmentally enriched rats, ethanol attenuated stress ulcer development relative to their non-ethanol-exposed but stressed controls. In nonstressed enriched rats, ethanol alone exacerbated stomach damage. We suggest that environmental rearing conditions markedly influence the complex interaction between ethanol intake and the response to stress.

Red spinach (Amaranthus tricolor L.) ethanolic extract as prevention against atherosclerosis based on the level of Low-Density Lipoprotein and histopathological feature of aorta in male Sprague-Dawley rats

NASA Astrophysics Data System (ADS)

Pradana, Dimas Adhi; Pondawinata, Marizki; Widyarini, Sitarina

2017-03-01

This study aimed to determine the potential activity of standardized ethanolic extract of red spinach as prevention against atherosclerosis based on the level of Low-Density Lipoprotein (LDL) and histopathological feature of aorta in male Sprague-Dawley rats induced by high-fat, high-cholesterol diet. A total of 42 animals was divided into 6 groups: normal control group, negative control group, positive control group (0.9 mg/kgBW of simvastatin), first intervention group (200 mg/kgBW of red spinach extract), second intervention group (400 mg/kgBW of red spinach extract), and third intervention group (800 mg/kgBW of red spinach extract). From the first day up to the 66th day, all the groups, except the normal control group and negative control group, were administered simvastatin (positive control) and extract of amaranth (intervention). Then, from the eighth day until Day 66, induction of high-fat and high-cholesterol diet was given in two hours after the simvastatin and red spinach extract administration. The determination of LDL parameters was conducted on Day 0, Day 35, and Day 67. On the 67th day, the animals were dissected to examine the aortic histopathological parameters. The results showed that the ethanolic extract of red spinach with a dose of 200 mg/kgBW, 400 mg/kgBW, and 800 mg/kgBW statistically demonstrated a significant difference (p<0.05). The histopathological feature of the aorta in the treatment indicated the absence of fat in the blood vessel walls or even of foam cells supporting thereby the result of LDL level. This means there was a significant effect of ethanolic extract of red spinach on the prevention against atherosclerosis based on the level of Low-Density Lipoprotein and the histopathological feature of aorta in male Sprague-Dawley rats.

Interactive effects of ethanol on ulcerative colitis and its associated testicular dysfunction in pubertal BALB/c mice.

PubMed

Adedara, Isaac A; Ajayi, Babajide O; Awogbindin, Ifeoluwa O; Farombi, Ebenezer O

2017-11-01

Available epidemiological reports have indicated an increase in the incidence of ulcerative colitis, as well as alcohol consumption, globally. The present study investigated the possible interactive effects of ethanol consumption on ulcerative colitis and its associated testicular dysfunction using six groups of 12 pubertal mice each. Group I (Control) mice received drinking water alone. Group II mice received ethanol alone at 5 g/kg body weight. Group III mice received 2.5% dextran sulphate sodium (DSS) in drinking water followed by normal drinking water. Groups IV, V, and VI mice received DSS followed by ethanol at 1.25, 2.5, and 5 g/kg, respectively. Administration of ethanol to mice with ulcerative colitis intensified the disease-activity index with marked reduction in colon length, colon mass index, body weight gain, and organo-somatic indices of testes and epididymis when compared with the DSS-alone group. Moreover, ethanol exacerbated colitis-mediated decrease in enzymatic and non-enzymatic antioxidants but increased the oxidative stress and inflammatory biomarkers in the testes and epididymis. The diminution in luteinizing hormone, follicle stimulating hormone, and testosterone levels was intensified following administration of ethanol to mice with ulcerative colitis that were administered 5 g/kg ethanol alone. The decrease in sperm functional parameters and testicular spermatogenic indices as well as histopathological damage in colon, testes, and epididymis was aggravated following administration of ethanol to mice with ulcerative colitis. In conclusion, the exacerbating effects of ethanol on ulcerative colitis-induced testicular dysfunction are related to increased oxidative stress and inflammation in the treated mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Ethanol Extract of Haliclona sp. Improved Histological Grade of Mammary Adenocarcinoma in C3H Mice

NASA Astrophysics Data System (ADS)

Murwani, R.; Trianto, A.; Wijayanti, E.; Ridlo, A.; Susilaningsih, N.

2018-02-01

The sponge Haliclona sp. contains secondary metabolites belong to alkaloids which are cytotoxic to the human tumor. The following research was conducted to study the effect of a graded level of Haliclona sp. extract on mammary adenocarcinoma in C3H mice. Haliclona sp. was obtained from Bandengan water in Jepara, and the crude extract was prepared by maceration with ethanol. Fifteen C3H mice with an initial weight of 20-25 gram were assigned into control, H-1, and H-2 groups. Control, H1, and H2 groups each received the ethanol extract of 0, 0.15, and 1.5 mg per mouse per day respectively for two weeks. Cancer cells were introduced to all groups from a cancerous donor mouse. The donor cancer cells were injected into each mouse via left or right axilla and allowed to grow. The cancer mass was removed and processed for histological examination, and the cancer growth was determined according to Elston and Ellis criteria. The result showed that histological grade of cancer mass from control group was in grade 2 or differentiated moderately. The histological grade of cancer mass from H-1 and H-2 groups were in grade 1 or similar to a normal cell. Analyses of the data by Kruskal-Wallis showed a significant difference (p<0,05) between control and treated groups. No significant difference was found between H-1 and H-2 groups. The results suggest the potential of active substances in the ethanol extract of Haliclona sp as an anti-cancer drug.

Ethanol Consumption by Wistar Rat Dams Affects Selenium Bioavailability and Antioxidant Balance in Their Progeny

PubMed Central

Ojeda, María Luisa; Vázquez, Beatriz; Nogales, Fátima; Murillo, María Luisa; Carreras, Olimpia

2009-01-01

Ethanol consumption affects maternal nutrition, the mothers’ antioxidant balance and the future health of their progeny. Selenium (Se) is a trace element cofactor of the enzyme glutathione peroxidase (GPx). We will study the effect of ethanol on Se bioavailability in dams and in their progeny. We have used three experimental groups of dams: control, chronic ethanol and pair-fed; and three groups of pups. Se levels were measured by graphite-furnace atomic absorption spectrometry. Serum and hepatic GPx activity was determined by spectrometry. We have concluded that ethanol decreased Se retention in dams, affecting their tissue Se deposits and those of their offspring, while also compromising their progeny’s weight and oxidation balance. These effects of ethanol are caused by a reduction in Se intake and a direct alcohol-generated oxidation action. PMID:19742151

Mechanisms of Gastroprotective Effects of Ethanolic Leaf Extract of Jasminum sambac against HCl/Ethanol-Induced Gastric Mucosal Injury in Rats

PubMed Central

AlRashdi, Ahmed S.; Salama, Suzy M.; Alkiyumi, Salim S.; Abdulla, Mahmood A.; Hadi, A. Hamid A.; Abdelwahab, Siddig I.; Taha, Manal M.; Hussiani, Jamal; Asykin, Nur

2012-01-01

Jasminum sambac is used in folk medicine as the treatment of many diseases. The aim of the present investigation is to evaluate the gastroprotective effects of ethanolic extracts of J. sambac leaves against acidified ethanol-induced gastric ulcers in rats. Seven groups of rats were orally pre-treated with carboxymethylcellulose (CMC) as normal group, CMC as ulcer group, 20 mg/kg of omeprazole as positive group, 62.5, 125, 250, and 500 mg/kg of extract as the experimental groups, respectively. An hour later, CMC was given orally to normal group and acidified ethanol solution was given orally to the ulcer control, positive control, and the experimental groups. The rats were sacrificed after an hour later. Acidity of gastric content, the gastric wall mucus, ulcer areas, and histology and immunohistochemistry of the gastric wall were assessed. Gastric homogenates were determined for prostaglandin E2 (PGE2), superoxide dismutase (SOD), andmalondialdehyde (MDA) content. Ulcer group exhibited significantly severe mucosal injury as compared with omeprazole or extract which shows significant protection towards gastric mucosal injury the plant promotes ulcer protection as it shows significant reduction of ulcer area grossly, and histology showed marked reduction of edema and leucocytes infiltration of submucosal layer compared with ulcer group. Immunohistochemistry showed overexpression of Hsp70 protein and downexpression of Bax protein in rats pretreated with extract. Significant increased in the pH, mucus of gastric content and high levels of PGE2, SOD and reduced amount of MDA was observed. PMID:22550543

Six-month evaluation of adhesives interface created by a hydrophobic adhesive to acid-etched ethanol-wet bonded dentine with simplified dehydration protocols.

PubMed

Sadek, Fernanda T; Mazzoni, Annalisa; Breschi, Lorenzo; Tay, Franklin R; Braga, Roberto R

2010-04-01

To evaluate the efficacy of simplified dehydration protocols, in the absence of tubular occlusion, on bond strength and interfacial nanoleakage of a hydrophobic experimental adhesive blend to acid-etched, ethanol-dehydrated dentine immediately and after 6 months. Molars were randomly assigned to 6 treatment groups (n=5). Under pulpal pressure simulation, dentine crowns were acid-etched with 35% H(3)PO(4) and rinsed with water. Adper Scotchbond Multi-Purpose was used for the control group. The remaining groups had their dentine surface dehydrated with ethanol solutions: group 1=50%, 70%, 80%, 95% and 3x100%, 30s for each application; group 2 the same ethanol sequence with 15s for each solution; groups 3, 4 and 5 used 100% ethanol only, applied in seven, three or one 30s step, respectively. After dehydration, a primer (50% BisGMA+TEGDMA, 50% ethanol) was used, followed by the neat comonomer adhesive application. Resin composite build-ups were then prepared using an incremental technique. Specimens were stored for 24h, sectioned into beams and stressed to failure after 24h or after 6 months of artificial ageing. Interfacial silver leakage evaluation was performed for both storage periods (n=5 per subgroup). Group 1 showed higher bond strengths at 24h or after 6 months of ageing (45.6+/-5.9(a)/43.1+/-3.2(a)MPa) and lower silver impregnation. Bond strength results were statistically similar to control group (41.2+/-3.3(ab)/38.3+/-4.0(ab)MPa), group 2 (40.0+/-3.1(ab)/38.6+/-3.2(ab)MPa), and group 3 at 24h (35.5+/-4.3(ab)MPa). Groups 4 (34.6+/-5.7(bc)/25.9+/-4.1(c)MPa) and 5 (24.7+/-4.9(c)/18.2+/-4.2(c)MPa) resulted in lower bond strengths, extensive interfacial nanoleakage and more prominent reductions (up to 25%) in bond strengths after 6 months of ageing. Simplified dehydration protocols using one or three 100% ethanol applications should be avoided for the ethanol-wet bonding technique in the absence of tubular occlusion, as they showed decreased bond strength, more severe nanoleakage and reduced bond stability over time. Copyright 2009 Elsevier Ltd. All rights reserved.

High doses of alcohol during pregnancy cause DNA damages in osteoblasts of newborns rats.

PubMed

Carvalho, Isabel Chaves Silva; Dutra, Tamires Pereira; Andrade, Dennia Perez De; Balducci, Ivan; Pacheco-Soares, Cristina; Rocha, Rosilene Fernandes da

2016-02-01

Alcohol exerts teratogenic effects and its consumption during pregnancy can cause deficit of bone development. The aim of the current study was to evaluate the genotoxic effects of prenatal exposure to ethanol on newborn rat osteoblasts. Wistar rats were initially divided into two groups: Ethanol group which received Ethanol 20% V/V in liquid diet and solid diet ad libitum, and Control group, which received solid diet and water ad libitum. Each group received a specific diet for 8 weeks before breeding and throughout three weeks of gestation and the treatment was finished on the day the pups were killed. On the fifth day of life, the pups from each group were killed for removal of the calvaria and isolation of osteogenic cells by sequential enzymatic digestion. The cells were cultured for a maximum period of 14 days. The detection of genotoxic effects of alcohol was investigated by the comet and the micronucleus assay. Micronucleus and comet assay showed significant increases in DNA damage at 7 days in Ethanol group (p = 0.0302, p = 0.0446, respectively). However, at 14 days both assay showed no significant difference between the groups (p = 0.6194, p = 0.8326, respectively). Our results showed that prenatal exposure to ethanol induced DNA damage in osteoblasts, as shown by micronucleus formation and higher percentage of DNA in the comet tail. It can be concluded that prenatal exposure to ethanol damages osteoblast DNA in newborns exposed to high doses of ethanol during pregnancy, suggesting that prenatal ethanol consumption has a direct effect on fetal osteoblasts. © 2015 Wiley Periodicals, Inc.

Effects of ethanol on social avoidance induced by chronic social defeat stress in mice.

PubMed

Favoretto, Cristiane A; Macedo, Giovana C; Quadros, Isabel M H

2017-01-01

In rodents, chronic social defeat stress promotes deficits in social interest and social interaction. We further explored these antisocial effects by comparing the consequences of two different defeat stress protocols (episodic vs. continuous stress) in a social investigation test. We expected that continuous, but not episodic, stress would induce social deficits in this model. Furthermore, we tested whether a potentially anxiolytic dose of ethanol reverses social deficits induced by defeat stress. Male Swiss mice were exposed to a 10-day social defeat protocol, using daily confrontations with an aggressive resident mouse. Episodic stress consisted of brief defeat episodes, after which the defeated mouse was returned to its home cage, until the next defeat 24 h later (n = 7-11/group). For continuous stress, similar defeat episodes were followed by cohabitation with the aggressive resident for 24 h, separated by a perforated divider, until the following defeat (n = 8-14/group). Eight days after stress termination, defeated and control mice were assessed in a social investigation test, after treatment with ethanol (1.0 g/kg, i.p.) or 0.9% saline. Considering the time spent investigating a social target, mice exposed to episodic or continuous social stress showed less social investigation than controls (p < .05). Deficits in social interest were not reversed by acute ethanol treatment. However, ethanol reduced time spent in social interaction in one control group (p < .05). Locomotor activity was not affected by social stress or ethanol. Thus, a history of social defeat stress, whether episodic or continuous, promotes deficits in social investigation that were not reversed by acute treatment with ethanol.

Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations.

PubMed

Ramlan, Nurul Farhana; Sata, Nurul Syafida Asma Mohd; Hassan, Siti Norhidayah; Bakar, Noraini Abu; Ahmad, Syahida; Zulkifli, Syaizwan Zahmir; Abdullah, Che Azurahanim Che; Ibrahim, Wan Norhamidah Wan

2017-08-14

Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors, decreases ethanol consumption in alcohol-preferring UChB rats.

PubMed

Quiroz, Gabriel; Guerra-Díaz, Nicolás; Iturriaga-Vásquez, Patricio; Rivera-Meza, Mario; Quintanilla, María Elena; Sotomayor-Zárate, Ramón

2018-09-03

Alcohol abuse is a worldwide health problem with high economic costs to health systems. Emerging evidence suggests that modulation of brain nicotinic acetylcholine receptors (nAChRs) may be a therapeutic target for alcohol dependence. In this work, we assess the effectiveness of four doses of erysodine (1.5, 2.0, 4.0 or 8.0 mg/kg/day, i.p.), a competitive antagonist of nAChRs, on voluntary ethanol consumption behavior in alcohol-preferring UChB rats, administered during three consecutive days. Results show that erysodine administration produces a dose-dependent reduction in ethanol consumption respect to saline injection (control group). The highest doses of erysodine (4 and 8 mg/kg) reduce (45 and 66%, respectively) the ethanol intake during treatment period and first day of post-treatment compared to control group. While, the lowest doses of erysodine (1.5 and 2 mg/kg) only reduce ethanol intake during one day of treatment period. These effective reductions in ethanol intake were 23 and 29% for 1.5 and 2 mg/kg erysodine, respectively. Locomotor activity induced by a high dose of erysodine (10 mg/kg) was similar to those observed with saline injection in control rats, showing that the reduction in ethanol intake was not produced by hypolocomotor effect induced by erysodine. This is the first report showing that erysodine reduces ethanol intake in UChB rats in a dose-dependent manner. Our results highlight the role of nAChRs in the reward effects of ethanol and its modulation as a potentially effective pharmacological alternative for alcohol dependence treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats

PubMed Central

Hosseini, Sayed Masoud; Taghiabadi, Elahe; Abnous, Khalil; Hariri, Alireza Timcheh; Pourbakhsh, Hamed; Hosseinzadeh, Hossein

2017-01-01

Objective(s): Long term consumption of ethanol may induce damage to many organs. Ethanol induces its noxious effects through reactive oxygen species production, and lipid peroxidation and apoptosis induction in different tissues and cell types. Previous experiments have indicated the antioxidant characteristics of thymoquinone, the active constituent of Nigella sativa fixed oil, against biologically dangerous reactive oxygen species. This experiment was planned to evaluate the protective effect of thymoquinone against subchronic ethanol toxicity in rats. Materials and Methods: Experiments were performed on six groups. Each group consisted of six animals, including control group (saline, gavage), ethanol-receiving group (3 g/kg/day, gavage), thymoquinone (2.5, 5, 10 mg/Kg/day, intraperitoneally (IP)) plus ethanol and thymoquinone (10 mg/Kg/day, IP) groups. Treatments were carried out in four weeks. Results: Thymoquinone reduced the ethanol-induced increase in the lipid peroxidation and severity of histopathological alteration in liver and kidney tissues. In addition it improved the levels of proinflammatory cytokines in liver tissue. Furthermore, thymoquinone corrected the liver enzymes level including alanine transaminase, aspartate transaminase and alkaline phosphatase in serum and glutathione content in liver and kidney tissues. Other experiments such as Western blot analysis and quantitative real-time RT-PCR revealed that thymoquinone suppressed the expression of Bax/Bcl-2 ratio (both protein and mRNA level), and caspases activation pursuant to ethanol toxicity. Conclusion: This study indicates that thymoquinone may have preventive effects against ethanol toxicity in the liver and kidney tissue through reduction in lipid peroxidation and inflammation, and also interrupting apoptosis. PMID:29085585

Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys

PubMed Central

Miller, R T; Miksys, S; Hoffmann, E; Tyndale, R F

2014-01-01

BACKGROUND AND PURPOSE CYP2D6 metabolizes many centrally acting drugs, neurotoxins and endogenous neurochemicals, and differences in brain levels of CYP2D have been associated with brain function and drug response. Alcohol consumers and smokers have higher levels of CYP2D6 in brain, but not liver, suggesting ethanol and/or nicotine may induce human brain CYP2D6. We investigated the independent and combined effects of chronic ethanol self-administration and nicotine treatment on CYP2D expression in African green monkeys. EXPERIMENTAL APPROACH Forty monkeys were randomized into control, ethanol-only, nicotine-only and ethanol + nicotine groups. Two groups voluntarily self-administered 10% ethanol in sucrose solution for 4 h·day−1, whereas two groups consumed sucrose solution on the same schedule. Two groups received daily s.c. injections of 0.5 mg·kg−1 nicotine in saline bid, whereas two groups were injected with saline on the same schedule. KEY RESULTS Both nicotine and ethanol dose-dependently increased CYP2D in brain; brain mRNA was unaffected, and neither drug altered hepatic CYP2D protein or mRNA. The combination of ethanol and nicotine increased brain CYP2D protein levels to a greater extent than either drug alone (1.2–2.2-fold, P < 0.05 among the eight brain regions assessed). Immunohistochemistry revealed the induction of brain CYP2D protein within specific cell types and regions in the treatment groups. CONCLUSIONS AND IMPLICATIONS Ethanol and nicotine increase brain CYP2D protein levels in monkeys, in a region and treatment-specific manner, suggesting that CNS drug responses, neurodegeneration and personality may be affected among people who consume alcohol and/or nicotine. PMID:24611668

Effects of ethanol on superovulation in the immature rat following pregnant mare's serum gonadotropin (PMSG) or PMSG and human chorionic gonadotropin treatment.

PubMed

Bo, W J; Krueger, W A; Rudeen, P K

1983-05-01

We sought to determine whether superovulation could occur in immature rats on a 5% ethanol diet and treated with pregnant mare's serum gonadotropin (PMSG) alone or with human chorionic gonadotropin (hCG). Holtzman female rats were divided into five groups at 20 days of age. Six rats (Group I) were killed at that age. Ten rats (Group II) were placed on an ad libitum laboratory chow diet and killed on Day 33. Twenty-four rats (Group III) were placed on an ad libitum laboratory chow diet. Twenty-four rats (Group IV) were placed on 5% ethanol liquid diet, while 24 rats in Group V were pair-fed with the animals in Group IV. At 30 days of age, 12 rats from each Group, III, IV, and V, received 25 IU of PMSG s.c. and were killed 74-76 h later. The remaining 12 rats from each Group, III, IV and V, received 25 IU of PMSG and 54-56 h later received 10 IU of hCG and were killed 20 h later. Ovulation occurred in all the rats of Groups III and V that received PMSG alone or with hCG. In the ethanol-treated rats that received PMSG alone, 75% ovulated, while 92% ovulated that received PMSG and hCG. The number of ova shed in the ethanol-PMSG-treated rats was significantly less than in the ethanol-PMSG-hCG-treated animals and in the controls. The uterine weights and morphology of the animals in Group IV were similar to those in Groups III and V. The study indicates that ethanol does not have a direct gonadotoxic effect on the ovary but indicates that ethanol has an effect on the hypothalamus and/or the pituitary, thereby disrupting the synthesis and/or release of luteinizing hormone releasing hormone (LHRH) or luteinizing hormone (LH).

Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol-3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In Rats.

PubMed

Tayeby, Faezeh; Salman, Abbas Abdul Ameer; Kamran, Sareh; Khaing, Si Lay; Salehen, Nur'ain Binti; Mohan, Gokula Mohan A/L Duchiyanda

2017-01-01

The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)-methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The aim of this research investigation was to evaluate the acute toxicity and the ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy methyl cellulose) for the normal and ulcer control groups each, Omeprazole (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for experimental groups, respectively. After one hour, instead of rats in the normal group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice, gastric mucosa, morphologies of gastric ulcers and protein expressions of both control and treatment groups were evaluated. TIBH showed a ulcer prevention potential by increase of the mucus secretion, decrease of the gastric acidity, up-regulation of HSP70 protein, down-regulation of Bax protein, decrease of the lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in gastric tissue homogenate. Acute toxicity assay exposed valuable information on the safety of this compound. TIBH had a dose dependent ulcer prevention potential against HCl/Ethanol-triggered gastric ulcer.

Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol-3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In Rats

PubMed Central

Tayeby, Faezeh; Salman, Abbas Abdul Ameer; Kamran, Sareh; Khaing, Si Lay; Salehen, Nur'ain Binti; Mohan, Gokula Mohan A/L Duchiyanda

2017-01-01

The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)-methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The aim of this research investigation was to evaluate the acute toxicity and the ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy methyl cellulose) for the normal and ulcer control groups each, Omeprazole (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for experimental groups, respectively. After one hour, instead of rats in the normal group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice, gastric mucosa, morphologies of gastric ulcers and protein expressions of both control and treatment groups were evaluated. TIBH showed a ulcer prevention potential by increase of the mucus secretion, decrease of the gastric acidity, up-regulation of HSP70 protein, down-regulation of Bax protein, decrease of the lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in gastric tissue homogenate. Acute toxicity assay exposed valuable information on the safety of this compound. TIBH had a dose dependent ulcer prevention potential against HCl/Ethanol-triggered gastric ulcer. PMID:29200945

Effects of glutamine administration on inflammatory responses in chronic ethanol-fed rats.

PubMed

Peng, Hsiang-Chi; Chen, Ya-Ling; Chen, Jiun-Rong; Yang, Sien-Sing; Huang, Kuan-Hsun; Wu, Yi-Chin; Lin, Yun-Ho; Yang, Suh-Ching

2011-03-01

The purpose of this study was to investigate the effects of glutamine supplementation on inflammatory responses in chronic ethanol-fed rats. Male Wistar rats weighing about 160 g were divided into five groups. Two groups were fed a normal liquid diet and three groups were fed a glutamine-containing liquid diet. After 1 week, one of the normal liquid diet groups was fed an ethanol-containing liquid diet (CE), and the other group served as the control (CC) group. At the same time, one of the glutamine-containing liquid diet groups was continually fed the same diet (GCG), but the other two groups were fed ethanol-containing diet supplemented with glutamine (GEG) or without glutamine (GE). The following items were analyzed: (1) liver function, (2) cytokine contents, and (3) hepatic oxidative stress. The activities of aspartate transaminase (AST) and alanine transaminase (ALT) and levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the CE group had significantly increased. In addition, hepatic cytochrome P450 2E1 (CYP2E1) expression had significantly increased in the CE, GE and GEG groups. However, the activities of AST and ALT and levels of TNF-α and IL-1β in the GE group were significantly lower than those of the CE group. The results suggest that the plasma inflammatory responses of rats fed an ethanol-containing liquid diet for 7 weeks significantly increased. However, pretreatment with glutamine improved the plasma inflammatory responses induced by ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

The pathogenesis of ethanol versus methionine and choline deficient diet-induced liver injury.

PubMed

Gyamfi, Maxwell Afari; Damjanov, Ivan; French, Samuel; Wan, Yu-Jui Yvonne

2008-02-15

The differences and similarities of the pathogenesis of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH) were examined. Mice (six/group) received one of four Lieber-Decarli liquid diets for 6 weeks: (1) paired-fed control diet; (2) control diet with ethanol (ethanol); (3) paired-fed methionine/choline deficient (MCD) diet; and (4) MCD plus ethanol (combination). Hepatotoxicity, histology, and gene expression changes were examined. Both MCD and ethanol induced macrovesicular steatosis. However, the combination diet produced massive steatosis with minor necrosis and inflammation. MCD and combination diets, but not ethanol, induced serum ALT levels by 1.6- and 10-fold, respectively. MCD diet, but not ethanol, also induced serum alkaline phosphatase levels suggesting bile duct injury. Ethanol increased liver fatty acid binding protein (L-FABP) mRNA and protein levels. In contrast, the combination diet decreased L-FABP mRNA and protein levels and increased hepatic free fatty acid and lipid peroxide levels. Ethanol, but not MCD, reduced hepatic S-adenosylmethionine (SAM) and GSH levels. Hepatic TNFalpha protein levels were increased in all treatment groups, however, IL-6, a hepatoprotective cytokine which promotes liver regeneration was increased in ethanol-fed mice (2-fold), but decreased in the combination diet-treated mice. In addition, the combination diet reduced phosphorylated STAT3 and Bcl-2 levels. While MCD diet might cause bile duct injury and cholestasis, ethanol preferentially interferes with the SAM-GSH oxidative stress pathway. The exacerbated liver injury induced by the combination diet might be explained by reduced L-FABP, increased free fatty acids, oxidative stress, and decreased IL-6 protein levels. The combination diet is an efficient model of steatohepatitis.

Chlorogenic Acid Prevents Alcohol-induced Brain Damage in Neonatal Rat.

PubMed

Guo, Zikang; Li, Jiang

2017-01-01

The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells.

Amelioration of cisplatin-induced nephrotoxicity by ethanolic extract of Bauhinia purpurea: An in vivo study in rats.

PubMed

Rana, Md Azmat; Khan, Rahat Ali; Nasiruddin, Mohammad; Khan, Aijaz Ahmed

2016-01-01

Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dose-dependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats.

Chronic ethanol use in alcoholic beverages by HIV-infected patients affects the therapeutic window of stavudine, lamivudine and nevirapine during the 9-month follow-up period: using chronic alcohol-use biomarkers.

PubMed

Bbosa, Godfrey S; Kyegombe, David B; Anokbonggo, William W; Ogwal-Okeng, Jasper; Musoke, David; Odda, John; Lubega, Aloysius; Ntale, Muhammad

2014-01-27

Abstract Background: Chronic ethanol use is a global problem including among HIV-infected patients on stavudine/lamivudine/nevirapine (d4T/3TC/NVP) regimen. The study determined the effect of chronic ethanol use on the therapeutic window of d4T, 3TC and NVP in HIV-infected patients using alcohol-use biomarkers to screen patients for chronic ethanol use. Methods: A case-control study using repeated measures design with serial measurements was used to quantify drugs in plasma. The WHO alcohol use disorder identification test (AUDIT) tool was initially used to screen patients for chronic alcohol use, and then they were further sorted using alcohol-use bioamarkers (γ-glutamyl transferase ≥55.0 IU; mean corpuscular volume, ≥96 fl, aspartate amino transferase/alanine aminotransferase ratio ≥2.0 value). A total of 41 patients (26 in the alcohol group and 15 in the control group) were followed up for 9 months with blood sampling done at 3-month intervals. Plasma drug concentrations were quantified using a Shimadzu Class-VP™ HPLC data system version 6.1. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed model. Means were compared using Student's t-test. Results: The mean steady-state plasma drug concentrations of d4T and 3TC in the alcohol group were lower than that in the control group during the 9-month period of follow-up. For 3TC, there was a statistical difference in the mean steady-state plasma drug concentrations between the alcohol group and the control group (p≤0.05) in the 6- and 9-month period of follow-up. For NVP, in both groups they were within the reference ranges, although the drug plasma concentrations were higher in the alcohol group compared to the control group and were statistically significant (p<0.05) in 0, 3 and 6 months of follow-up. Conclusions: Chronic ethanol use by HIV-infected patients reduced the therapeutic steady-state plasma drug concentrations of d4T and 3TC and increased the NVP drug concentrations in the HIV-infected patients.

Effects of different concentrations of sugarcane alcohol on food intake and nutritional status of male and female periadolescent rats.

PubMed

Gonçalves de Orange, Luciana; Bion, Francisca Martins; Rolim de Lima, Cybelle

2009-03-01

The present study evaluated the effects of food and alcohol intake on the nutritional and metabolic status of male and female periadolescent rats submitted to single (15%) and multiple (10%, 20%, 30%) concentrations of hydroalcoholic solutions of sugar-based alcohol associated with a feed mixture. Thirty-six periadolescent Wistar rats were used and randomly arranged into three groups: Group A (control; 0% ethanol; six males and six females), Group B (15% ethanol; six males and six females), and Group C (10%, 20%, and 30% ethanol; six males and six females). Food consumption, body weight, water intake (mL), ethanol intake (g/kg/day), ethanol preference in relation to water and different concentrations, and serum biochemical dosages (glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein fraction, triglycerides, cholesterol/HDL [CT/HDL], albumin) were analyzed. Males from Group C ingested more feed than females, which consumed reducing amounts throughout the weeks studied. Males also had heavier body weight, which increased throughout the experimental period. The animals ingested more water (females ingested more than males) in the first experimental week. Group C had a higher ethanol intake and greater preference for ethanol over water in both genders than Group B, which decreased over the subsequent weeks. Serum glucose was lower in Group A, whereas the CT/HDL ratio was lower in Group C. These findings allow the conclusion that nutritional and metabolic impact resulting from alcohol intake is different between genders and between the different forms in which the drug is offered. It is important to warn the population about the concentrations of alcohol intake, which may influence the growth and development of adolescents, thereby compromising their quality of life.

The effects of ethanol and strontium on growth and development of two-cell arrested mouse embryos.

PubMed

Darabi, Mohammad Reza; Shiravi, Abdolhossein; Hojati, Vida

2012-01-01

Arresting at a certain stage of development like the two-cell stage could be one of the causes of infertility. The aim of this study is to evaluate the effects of ethanol and strontium on growth and development of mice embryos arrested at the two-cell stage. In this experimental study, female mice were coupled with a male following superovulation. Positive vaginal plug mice were sacrificed 48 hours after human chorionic gonadotropin (hCG) injection. Two-cell embryos were transferred to M16 medium and divided to four groups. The first control group was incubated without any exposure to low temperatures. Groups 2, 3 and 4 were exposed to 4°C for 24 hours. The second control group was incubated immediately, while the third and fourth groups were exposed to 10 mM strontium for five minutes and 0.1% ethanol for a further five minutes. Growth rate and developmental parameters of embryos were analyzed by one- way ANOVA. The significant difference between the groups was determined by Post Hoc. The data shows that developmental rate is decreased significantly by 4°C exposure. The mean percentage of degenerated embryo was significantly different between groups but the mean cleavage rate was not significantly different. The mean percent of morula, blastocyst and hatched blastocyst formation were significantly different between groups during a 120 hours study post hCG injection. The effect of strontium and ethanol on arrested two-cell embryos had no significant effect on the mean percentage of morula, but ethanol treatment significantly increased the percentage of blastocyst and hatched blastocyst formation compared to strontium.

Autoshaping induces ethanol drinking in nondeprived rats: evidence of long-term retention but no induction of ethanol preference.

PubMed

Tomie, Arthur; Kuo, Teresa; Apor, Khristine R; Salomon, Kimberly E; Pohorecky, Larissa A

2004-04-01

The effects of autoshaping procedures (paired vs. random) and sipper fluid (ethanol vs. water) on sipper-directed drinking were evaluated in male Long-Evans rats maintained with free access to food and water. For the paired/ethanol group (n=16), autoshaping procedures consisted of presenting the ethanol sipper (containing 0% to 28% unsweetened ethanol) conditioned stimulus (CS) followed by the response-independent presentation of food unconditioned stimulus (US). The random/ethanol group (n=8) received the sipper CS and food US randomly with respect to one another. The paired/water group (n=8) received only water in the sipper CS. The paired/ethanol group showed higher grams per kilogram ethanol intake than the random/ethanol group did at ethanol concentrations of 8% to 28%. The paired/ethanol group showed higher sipper CS-directed milliliter fluid consumption than the paired/water group did at ethanol concentrations of 1% to 6%, and 15%, 16%, 18%, and 20%. Following a 42-day retention interval, the paired/ethanol group showed superior retention of CS-directed drinking of 18% ethanol, relative to the random/ethanol group, and superior retention of CS-directed milliliter fluid drinking relative to the paired/water group. When tested for home cage ethanol preference using limited access two-bottle (28% ethanol vs. water) procedures, the paired/ethanol and random/ethanol groups did not differ on any drinking measures.

The body composition and lipid metabolic effects of long-term ethanol feeding during a high omega 6 polyunsaturated fatty acid diet in micropigs.

PubMed

Nakamura, M T; Tang, A B; Villanueva, J; Halsted, C H; Phinney, S D

1993-10-01

Our previous research with miniature pigs has shown that long-term ethanol feeding with a low-fat diet decreases arachidonic acid (20:4 omega 6) levels in multiple tissues, but we did not find significant liver pathology. In this study, we investigated the effect of ethanol feeding with high dietary linoleic acid (18:2 omega 6) on tissue fatty acid (FA) profiles and body composition. Five Yucatan micropigs were fed 370 kJ (89 kcal)/kg body weight of a diet containing ethanol and fat as 40% and 34% of energy, respectively; five control pigs were pair-fed corn starch in place of ethanol. Corn oil, 61% 18:2 omega 6, supplied most of the dietary fat. Liver biopsies were performed at baseline (n = 2 per group) and at three other time points (n = 5 per group). Phospholipid (PL) FA levels were measured by thin-layer and gas chromatography. Body composition was analyzed by underwater weighing of carcasses. Body composition analysis demonstrated a marked reduction of carcass fat in the ethanol group, but no significant reduction of carcass lean weight after 12 months. In liver PLs, the ethanol group showed decreased 20:4 omega 6 and docosahexaenoic acid (22:6 omega 3) after 1 month. While the decreased 20:4 omega 6 remained constant after 1 month, 22:6 omega 3 showed a progressive decrease up to 12-months, resulting in a continuous decrease of the omega 3/omega 6 FA ratio. This slowly progressive decrease in the omega 3/omega 6 ratio in liver PLs with ethanol feeding may have enhanced the inflammatory response in the liver, contributing to liver pathology. Body composition results indicate marked wasting of energy in the ethanol group.

Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine.

PubMed

Sogut, Ibrahim; Uysal, Onur; Oglakci, Aysegul; Yucel, Ferruh; Kartkaya, Kazim; Kanbak, Gungor

2017-03-01

Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy. Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei. Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments. We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.

Effect of melatonin on motor performance and brain cortex mitochondrial function during ethanol hangover.

PubMed

Karadayian, A G; Bustamante, J; Czerniczyniec, A; Cutrera, R A; Lores-Arnaiz, S

2014-06-06

Increased reactive oxygen species generation and mitochondrial dysfunction occur during ethanol hangover. The aim of this work was to study the effect of melatonin pretreatment on motor performance and mitochondrial function during ethanol hangover. Male mice received melatonin solution or its vehicle in drinking water during 7 days and i.p. injection with EtOH (3.8 g/kg BW) or saline at the eighth day. Motor performance and mitochondrial function were evaluated at the onset of hangover (6h after injection). Melatonin improved motor coordination in ethanol hangover mice. Malate-glutamate-dependent oxygen uptake was decreased by ethanol hangover treatment and partially prevented by melatonin pretreatment. Melatonin alone induced a decrease of 30% in state 4 succinate-dependent respiratory rate. Also, the activity of the respiratory complexes was decreased in melatonin-pretreated ethanol hangover group. Melatonin pretreatment before the hangover prevented mitochondrial membrane potential collapse and induced a 79% decrement of hydrogen peroxide production as compared with ethanol hangover group. Ethanol hangover induced a 25% decrease in NO production. Melatonin alone and as a pretreatment before ethanol hangover significantly increased NO production by nNOS and iNOS as compared with control groups. No differences were observed in nNOS protein expression, while iNOS expression was increased in the melatonin group. Increased NO production by melatonin could be involved in the decrease of succinate-dependent oxygen consumption and the inhibition of complex IV observed in our study. Melatonin seems to act as an antioxidant agent in the ethanol hangover condition but also exhibited some dual effects related to NO metabolism. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

THC inhibits the expression of ethanol-induced locomotor sensitization in mice.

PubMed

Filev, Renato; Engelke, Douglas S; Da Silveira, Dartiu X; Mello, Luiz E; Santos-Junior, Jair G

2017-12-01

The motivational circuit activated by ethanol leads to behavioral changes that recruit the endocannabinoid system (ECS). Case reports and observational studies suggest that the use of Cannabis sp. mitigates problematic ethanol consumption in humans. Here, we verified the effects of the two main phytocannabinoid compounds of Cannabis sp., cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), in the expression of ethanol-induced locomotor sensitization in mice. Male adult DBA/2 mice were exposed to locomotor sensitization by daily intraperitoneal injections of ethanol (2.5 g/kg) for 12 days; control groups received saline. After the acquisition phase, animals were treated with cannabinoids: CBD (2.5 mg/kg); THC (2.5 mg/kg); CBD + THC (1:1 ratio), or vehicle for 4 days with no access to ethanol during this period. One day after the last cannabinoid injection, all animals were challenged with ethanol (2.0 g/kg) to evaluate the expression of the locomotor sensitization. Mice treated with THC alone or THC + CBD showed reduced expression of locomotor sensitization, compared to the vehicle control group. No effects were observed with CBD treatment alone. Our findings showing that phytocannabinoid treatment prevents the expression of behavioral sensitization in mice provide insight into the potential therapeutic use of phytocannabinoids in alcohol-related problems. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats.

PubMed

Sathiavelu, Jayanthi; Senapathy, Giftson Jebakkan; Devaraj, Rajkumar; Namasivayam, Nalini

2009-06-01

To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

Ethanol disrupts chondrification of the neurocranial cartilages in medaka embryos without affecting aldehyde dehydrogenase 1A2 (Aldh1A2) promoter methylation

PubMed Central

Hu, Yuhui; Willett, Kristine L.; Khan, Ikhlas A.; Scheffler, Brian E.; Dasmahapatra, Asok K.

2009-01-01

Medaka (Oryzias latipes) embryos at different developmental stages were exposed to ethanol for 48 h, then allowed to hatch. Teratogenic effects were evaluated in hatchlings after examining chondrocranial cartilage deformities. Ethanol disrupted cartilage development in medaka in a dose and developmental stage-specific manner. Compared to controls, the linear length of the neurocranium and other cartilages were reduced in ethanol-treated groups. Moreover, the chondrification in cartilages, specifically trabeculae and polar cartilages, were inhibited by ethanol. To understand the mechanism of ethanol teratogenesis, NAD+: NADH status during embryogenesis and the methylation pattern of Aldh1A2 promoter in whole embryos and adult tissues (brain, eye, heart and liver) were analyzed. Embryos 6 dpf had higher NAD+ than embryos 0 or 2 dpf. Ethanol (200 or 400 mM) was able to reduce NAD+ content in 2 and 6 dpf embryos. However, in both cases reductions were not significantly different from the controls. Moreover, no significant difference in either NADH content or in NAD+: NADH status of the ethanol-treated embryos, with regard to controls, was observed. The promoter of Aldh1A2 contains 31 CpG dinucleotides (-705 to +154, ATG = +1); none of which were methylated. Compared to controls, embryonic ethanol exposure (100 and 400 mM) was unable to alter Aldh1A2 promoter methylation in embryos or in the tissues of adults (breeding) developmentally exposed to ethanol (300 mM, 48 hpf). From these data we conclude that ethanol teratogenesis in medaka does not induce alteration in the methylation pattern of Aldh1A2 promoter, but does change cartilage development. PMID:19651241

[Effect of flavonoids of ginkgo biloba on anti-oxidizing system of mice after acute alcohol administration].

PubMed

Yao, Ping; Liu, Lie-Gang; Jia, Wen-Bo; Song, Fang-Fang; Zhou, Shaoliang; Zhang, Xiping; Sun, Xiufa

2005-05-01

To investigate the protective effects of flavonoids of ginkgo biloba on anti-oxidizing system damaged by acute alcohol administration. Adult male Kunming mice were employed and divided into randomly flavonoid intervention group, normal control and ethanol control group according to body weight. After pretreated with flavonoids of ginkgo biloba (96mg/kg bw), the mice in flavonoid intervention group ingested alcohol (ethanol 4.8g/kg bw) via i.g. and were decapitated after 0.5, 1, 2, 4, 6, 9, and 15 h of ethanol administration. The same treatment was carried out on ethanol control group except that physiological saline was applied instead of flavonoid of ginkgo biloba. Meanwhile, the normal control group was established. The concentration of glutathione (GSH), malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) in the serum and liver were determined. The experiment displays that the content of GSH and the activities of GSH-Px and SOD decreased rapidly after 1 h of treatment with alcohol and dropped to the lowest level at 4h of treatment. After 6h of treatment, these indexes came to the normal level rapidly. The level of MDA of serum and liver increased rapidly after 1 h of treatment and reached the climax at 4h and 6h respectively. It went back to the normal concentration until 15h and 9 h respectively. On a whole, there were similar curves between flavonoids intervention group and alcohol control group on the indexes. However, to some extent, the supplement of flavonoid of ginkgo biloba can prohibit the rise of MDA level and the decline of GSH-Px, SOD, GSH which were induced by acute alcohol intakes. Flavonoid of ginkgo biloba have some protective effects on the damage of anti-oxidizing system of mice induced by acute alcohol adminstration.

Pancreatic polypeptide cells of rat pancreas after chronic ethanol feeding.

PubMed

Koko, V; Todorović, V; Drndarević, N; Glisić, R; Nedeljković, M; Nikolić, A

2001-05-01

Male Wistar rats, (2 months old) were randomly divided into two groups according to the diet offered (C-control and E-ethanol treated rats). Final body weight was significantly increased but pancreatic weight as a percentage of body weight was decreased in ethanol treated rats. Volume density, number of pancreatic poly peptide (PP)-cells per islet and per micron 2 of islet were significantly increased. PP-cells were abundant and occupied the whole periphery of islets in the splenic part of the pancreas. Those cells showed strong immunopositivity. At the ultrastructural level PP granules had predominantly less electron density. The mean diameter of PP granules was significantly increased and the number of granules of larger diameter was greater in the E group of rats, than in the controls.

Hepatic lipid profiling of deer mice fed ethanol using {sup 1}H and {sup 31}P NMR spectroscopy: A dose-dependent subchronic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernando, Harshica; Bhopale, Kamlesh K.; Boor, Paul J.

2012-11-01

Chronic alcohol abuse is a 2nd major cause of liver disease resulting in significant morbidity and mortality. Alcoholic liver disease (ALD) is characterized by a wide spectrum of pathologies starting from fat accumulation (steatosis) in early reversible stage to inflammation with or without fibrosis and cirrhosis in later irreversible stages. Previously, we reported significant steatosis in the livers of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup −}) vs. hepatic ADH-normal (ADH{sup +}) deer mice fed 4% ethanol daily for 2 months [Bhopale et al., 2006, Alcohol 39, 179–188]. However, ADH{sup −} deer mice fed 4% ethanol also showed a significant mortality. Therefore,more » a dose-dependent study was conducted to understand the mechanism and identify lipid(s) involved in the development of ethanol-induced fatty liver. ADH{sup −} and ADH{sup +} deer mice fed 1, 2 or 3.5% ethanol daily for 2 months and fatty infiltration in the livers were evaluated by histology and by measuring dry weights of extracted lipids. Lipid metabolomic changes in extracted lipids were determined by proton ({sup 1}H) and {sup 31}phosphorus ({sup 31}P) nuclear magnetic resonance (NMR) spectroscopy. The NMR data was analyzed by hierarchical clustering (HC) and principle component analysis (PCA) for pattern recognition. Extensive vacuolization by histology and significantly increased dry weights of total lipids found only in the livers of ADH{sup −} deer mice fed 3.5% ethanol vs. pair-fed controls suggest a dose-dependent formation of fatty liver in ADH{sup −} deer mouse model. Analysis of NMR data of ADH{sup −} deer mice fed 3.5% ethanol vs. pair-fed controls shows increases for total cholesterol, esterified cholesterol, fatty acid methyl esters (FAMEs), triacylglycerides and unsaturation, and decreases for free cholesterol, phospholipids and allylic and diallylic protons. Certain classes of neutral lipids (cholesterol esters, fatty acyl chain (-COCH{sub 2}-) and FAMEs) were also mildly increased in ADH{sup −} deer mice fed 1 or 2% ethanol. Only small increases were observed for allylic and diallylic protons, FAMEs and unsaturations in ADH{sup +} deer mice fed 3.5% ethanol vs. pair-fed controls. PCA of NMR data showed increased clustering by gradual separation of ethanol-fed ADH{sup −} deer mice groups from their respective pair-fed control groups and corresponding ethanol-fed ADH{sup +} deer mice groups. Our data indicate that dose of ethanol and hepatic ADH deficiency are two key factors involved in initiation and progression of alcoholic fatty liver disease. Further studies on characterization of individual lipid entities and associated metabolic pathways altered in our deer mouse model after different durations of ethanol feeding could be important to delineate mechanism(s) and identify potential biomarker candidate(s) of early stage ALD. -- Highlights: ► Dose-dependent ethanol-induced fatty liver was studied in deer mouse model. ► A NMR-based lipidomic approach with histology and dry lipid weights was used. ► We used principal component analysis (PCA) to analyze the NMR lipidomic data. ► Dose-dependent clustering patterns by PCA were compared among the groups.« less

Binge consumption of ethanol during pregnancy leads to significant developmental delay of mouse embryonic brain

NASA Astrophysics Data System (ADS)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2014-03-01

Consumption of alcohol during pregnancy can be severely detrimental to the development of the brain in fetuses. This study explores the usage of optical coherence tomography (OCT) to the study the effects of maternal consumption of ethanol on brain development in mouse fetuses. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde. A swept-source OCT (SSOCT) system was used to acquire 3D images of the brain of ethanol-exposed and control fetuses. The volume of right and left brain ventricles were measured and used to compare between ethanol-exposed and control fetuses. A total of 5 fetuses were used for each of the two groups. The average volumes of the right and left ventricles were measured to be 0.35 and 0.15 mm3 for ethanol-exposed and control fetuses, respectively. The results demonstrated that there is an alcohol-induced developmental delay in mouse fetal brains.

Hypolipidaemic Effect of Hericium erinaceum Grown in Artemisia capillaris on Obese Rats

PubMed Central

Choi, Won-Sik; Kim, Young-Sun; Park, Byeoung-Soo; Kim, Jang-Eok

2013-01-01

In this study, ethanolic extracts from Hericium erinaceum cultivated with Artemisia capillaris (HEAC) were assessed for their ability to lower the cholesterol levels of male Sprague-Dawley rats fed a high-fat diet. Rats were randomly subdivided into seven test groups. Each group contained eight rats fed a high-fat diet during a growth period lasting 4 wk. Supplementation with the extracts was performed once a day for 2 wk after the high-fat diet. The control group (rats fed a high-fat diet) showed a high efficiency ratio (feed efficiency ratio) value compared to the normal group. Biochemical parameters, including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglyceride (TG) levels dramatically increased in the control group compared to the normal group. High-density lipoprotein-cholesterol (HDL-c) content in the control group was also significantly lower relative to the normal group. Two positive control groups, treated with simvastatin and atorvastatin, had lowered TC, LDL-c, and TG levels, and increased HDL-c content compared to the control group. Treatment with the tested extracts, including HEAC, ethanolic extracts from Hericium erinaceum, and ethanolic extracts from Artemisia capillaris reduced TC, LDL-c, and TG levels and elevated HDL-c content in the hyperlipidemia rats. The atherogenic index and cardiac risk factor values for the HEAC-treated group were 0.95 and 1.95, respectively. Simvastatin- and atorvastatin-treated groups showed atherogenic index values of 1.56 and 1.69, respectively, and cardiac risk factor values of 2.56 and 2.69, respectively. These results show HEAC possesses an ability to cure hyperlipidemia in rats and may serve as an effective natural medicine for treating hyperlipidemia in humans. PMID:23874132

Hypolipidaemic Effect of Hericium erinaceum Grown in Artemisia capillaris on Obese Rats.

PubMed

Choi, Won-Sik; Kim, Young-Sun; Park, Byeoung-Soo; Kim, Jang-Eok; Lee, Sung-Eun

2013-06-01

In this study, ethanolic extracts from Hericium erinaceum cultivated with Artemisia capillaris (HEAC) were assessed for their ability to lower the cholesterol levels of male Sprague-Dawley rats fed a high-fat diet. Rats were randomly subdivided into seven test groups. Each group contained eight rats fed a high-fat diet during a growth period lasting 4 wk. Supplementation with the extracts was performed once a day for 2 wk after the high-fat diet. The control group (rats fed a high-fat diet) showed a high efficiency ratio (feed efficiency ratio) value compared to the normal group. Biochemical parameters, including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglyceride (TG) levels dramatically increased in the control group compared to the normal group. High-density lipoprotein-cholesterol (HDL-c) content in the control group was also significantly lower relative to the normal group. Two positive control groups, treated with simvastatin and atorvastatin, had lowered TC, LDL-c, and TG levels, and increased HDL-c content compared to the control group. Treatment with the tested extracts, including HEAC, ethanolic extracts from Hericium erinaceum, and ethanolic extracts from Artemisia capillaris reduced TC, LDL-c, and TG levels and elevated HDL-c content in the hyperlipidemia rats. The atherogenic index and cardiac risk factor values for the HEAC-treated group were 0.95 and 1.95, respectively. Simvastatin- and atorvastatin-treated groups showed atherogenic index values of 1.56 and 1.69, respectively, and cardiac risk factor values of 2.56 and 2.69, respectively. These results show HEAC possesses an ability to cure hyperlipidemia in rats and may serve as an effective natural medicine for treating hyperlipidemia in humans.

Aloe vera gel extract attenuates ethanol-induced hepatic lipid accumulation by suppressing the expression of lipogenic genes in mice.

PubMed

Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yamada, Muneo; Yamauchi, Kouji; Iwatsuki, Keiji

2012-01-01

We have previously reported that Aloe vera gel had hypoglycemic activity and anti-obesity effects, although the effect on alcoholic fatty liver was unclear. We examined in this present study the effect of an Aloe vera gel extract (AVGE) on hepatic lipid metabolism by using an ethanol-induced transient fatty liver mouse model. Ethanol (3 g/kg of mouse weight) was orally administered to induce an accumulation of triglyceride (TG) and increase the mRNA expression of such lipogenic genes as sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN) in the liver. Although ethanol ingestion caused a 5.4-fold increase in liver TG, pre-treating with AVGE (1 mg/kg/d) for 1 week significantly suppressed this elevation of the ethanol-induced liver TG level. The expression of lipogenic genes was also lower in the AVGE pre-treatment group than in the control group. This inhibitory effect on the ethanol-induced accumulation of TG was attributed to a reduction in the expression of lipogenic genes that were increased by ethanol.

Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride.

PubMed

Lin, Song-Chow; Lin, Chia-Hsien; Lin, Chun-Ching; Lin, Yun-Ho; Chen, Chin-Fa; Chen, I-Cheng; Wang, Li-Ya

2002-01-01

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s). Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

Evaluation of the Shear Bond Strength of Composite Resin to Wet and Dry Enamel Using Dentin Bonding Agents Containing Various Solvents.

PubMed

Usha, Carounanidy; Ramarao, Sathyanarayanan; John, Bindu Meera; Rajesh, Praveen; Swatha, S

2017-01-01

Bonding of composite resin to dentin mandates a wet substrate whereas, enamel should be dry. This may not be easily achievable in intracoronal preparations where enamel and dentin are closely placed to each other. Therefore, Dentin Bonding Agents (DBA) are recommended for enamel and dentinal bonding, where enamel is also left moist. A research question was raised if the "enamel-only" preparations will also benefit from wet enamel bonding and contemporary DBA. The aim of this study was to compare the shear bond strengths of composite resin, bonded to dry and wet enamel using fifth generation DBA (etch and rinse system) containing various solvents such as ethanol/water, acetone and ethanol. The crowns of 120 maxillary premolars were split into buccal and lingual halves. They were randomly allocated into four groups of DBA: Group 1-water/ethanol based, Group 2-acetone based, Group 3-ethanol based, Group 4-universal bonding agent (control group). The buccal halves and lingual halves were bonded using the wet bonding and dry bonding technique respectively. After application of the DBAs and composite resin build up, shear bond strength testing was done. Group 1 (ethanol/water based ESPE 3M, Adper Single Bond) showed highest bond strength of (23.15 MPa) in dry enamel. Group 2 (acetone based Denstply, Prime and Bond NT, showed equal bond strength in wet and dry enamel condition (18.87 MPa and 18.02 MPa respectively). Dry enamel bonding and ethanol/water based etch and rinse DBA can be recommended for "enamel-only" tooth preparations.

Antilipogenic and hypolipidemic effects of ethanol extracts from two variants of Artemisia princeps Pampanini in obese diabetic mice.

PubMed

Jung, Un Ju; Baek, Nam-In; Chung, Hae-Gon; Jeong, Tae-Sook; Lee, Kyung Tae; Lee, Mi-Kyung; Choi, Myung-Sook

2009-12-01

The objective of this study was to determine the effects of the ethanol extract of two variants of Artemisia princeps Pampanini, Sajabalssuk (SB) and Sajuarissuk (SS), on lipid metabolism in type 2 diabetic animals. Male C57BL/KsJ-db/db mice were divided into control, SB ethanol extract (SBE) (0.171 g/100 g of diet), SS ethanol extract (SSE) (0.154 g/100 g of diet), and rosiglitazone (RG) (0.005 g/100 g of diet) groups. Supplementation of SBE and SSE significantly lowered the plasma levels of free fatty acid, triglyceride, and total cholesterol compared to the control group. The hepatic triglyceride and cholesterol contents and hepatic lipid droplets accumulation were also significantly lower in the SBE- and SSE-supplemented db/db mice than in the control or RG-supplemented db/db mice. Reductions of hepatic triglyceride and cholesterol contents in the SBE and SSE groups were related to the suppression of hepatic lipogenic enzyme activities, fatty acid synthesis (fatty acid synthase and malic enzyme), triglyceride synthesis (phosphatidate phosphohydrolase), and cholesterol synthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and esterification (acyl-coenzyme A:cholesterol acyltransferase). The RG supplement lowered plasma and hepatic lipid levels compared to the control group. However, RG significantly increased the white and brown adipose tissue weight and epididymal adipocyte size, whereas SBE and SSE lowered the brown adipose tissue weight and epididymal adipocyte size compared to the RG group. Together, these data suggest that supplementation of SBE and SSE partly improves lipid dysregulation and fatty liver in db/db mice by suppressing hepatic lipogenic enzyme activities.

The Ethanolic Extracts The Gorgonian Isis hippuris Inhibited the Induced Mammary Carcinoma Growth In C3H Mice

NASA Astrophysics Data System (ADS)

Trianto, Agus; Andriyas, Yogi; Ridlo, Ali; Sedjati, Sri; Susilaningsih, Neni; Murwani, Retno

2018-02-01

The gorgonian Isis hippuris contains secondary metabolites gorgosterol and hippuristanol which are capable of inhibiting cancer cells. However, in vivo test of the gorgonian Isis hippuris extract as the anticancer drug has not been conducted. The research to study of the effect of ethanolic extract of the gorgonian on the induced tumor growth in C3H mice. The I. hippuris was obtained from Karimunjawa water in Jepara. The extract was prepared by maceration using ethanol. A total 20, 8-10 moths old of C3H mice with an initial weight of 20-25 gram were assigned into control, Ih-1, Ih-2, and Ih-3 groups. Control, Ih-1, Ih-2, and Ih-3 groups each received 0, 0.15, 1.5, and 15 mg extract per mouse per day respectively for two weeks. Cancer cells were introduced to all groups from a donor cancer mouse by injection via left or right axilla and allowed to grow. The cancer mass was removed and processed for histological examination, and cancer growth was determined according to Elston and Ellis criteria. The result showed that histological grade of cancer mass from the control group was in grade 2 or differentiated moderately. The histological grade of cancer mass from Ih-1, Ih-2, and Ih-3 groups were in grade 1 (low grade) or similar to a normal cell. Statistical analysis by Kruskal-Wallis test showed a significant difference (p<0,05) between control and treated mice. Mann-Whitney test found no significant differences among Ih-1, Ih-2, and Ih-3 treated mice. The results indicated the potential of active substances in the ethanol extract of I. hippuris as an anti-cancer drug.

Effect of caffeic acid phenethyl ester on oxidant and anti-oxidant status of liver and serum in a rat model with acute methanol intoxication.

PubMed

Yazgan, Ü C; Elbey, B; Kuş, S; Baykal, B; Keskin, I; Yılmaz, A; Şahin, A

2017-05-01

Methanol toxicity is one of the major public health problems because it can cause severe morbidity and mortality. Methanol intoxication causes changes in the balance between the production of free radicals and antioxidant capacity. We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on the total oxidant status, total antioxidant status (TAS), and oxidative stress index (OSI) parameters of the liver and the serum in a rat model of acute methanol intoxication. Rats were treated with intraperitoneal (i.p.) Methotrexate (MTX) for 7 days. On the 8th day, i.p. Methanol was administered in the methanol, ethanol and CAPE groups. Four hours after methanol treatment, ethanol was injected i.p. in the ethanol group; CAPE (i.p.) in the CAPE group; serum physiologic i.p. in other groups. After 8 hours, rats were killed and the serum and the liver samples were obtained for biochemical analyses. The OSI value was significantly higher in the methanol group compared to the ethanol and CAPE groups. Serum TAS levels of the methanol group were significantly different compared to the control group, but not compared to the MTX group. The amelioration of oxidative stress was greater in the CAPE group compared to the ethanol group but was not statistically significant. This study demonstrates that CAPE treatment ameliorates oxidative stress in the serum and liver in a rat model of acute methanol intoxication.

Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

PubMed Central

Chen, Sheng-Hsuan; Liang, Yu-Chih; Chao, Jane CJ; Tsai, Li-Hsueh; Chang, Chun-Chao; Wang, Chia-Chi; Pan, Shiann

2005-01-01

AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis. PMID:15968732

Chlorogenic Acid Prevents Alcohol-induced Brain Damage in Neonatal Rat

PubMed Central

Guo, Zikang; Li, Jiang

2017-01-01

Abstract The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells. PMID:29318034

Effects of Alcohol Injection in Rat Sciatic Nerve

PubMed Central

Mazoch, Mathew J.; Cheema, Gulraiz A.; Suva, Larry J.; Thomas, Ruth L.

2015-01-01

Background Previous studies have shown that the injection of dehydrated alcohol has been successful for the treatment of Morton's neuroma in the foot. In this study, we determined the cellular effect of injection of alcohol into and around the sciatic nerve of rats, and measured the extent of cell necrosis and/or any associated histologic or inflammatory changes. Methods Twenty-two male (~375g) Wistar rats were randomized into two groups each receiving alcohol injections into or around the sciatic nerve after nerve exposure under sterile technique. Group 1 rats were injected with a 0.5ml solution of 0.5% Marcaine in the left sciatic nerve as a control group. In the right sciatic nerve a 0.5ml solution of 4% ethanol with 0.5% Marcaine was injected. Group 2 rats received 0.5ml of 20%ethanol with 0.5% Marcaine injected into the left sciatic nerve and 0.5 ml of 30% ethanol with 0.5% Marcaine injected into the right sciatic nerve. In each group, the rats were placed in 3 subgroups: intraneural, perineural, perimuscular injections. All rats were sacrificed and tissue harvested for histologic evaluation at day 10 post injection. Results No evidence of alcohol-associated cell necrosis, apoptosis or apparent inflammation was observed in histologic specimens of any injected nerves, perineural tissue, or muscles in controls or experimental groups regardless of concentration of ethanol injected on day 10. Conclusion We concluded that alcohol injection (≤30% ethanol) into and/or around the sciatic nerve or the adjacent muscle of rats has no histologic evidence of necrosis or inflammation to the nerve or surrounding tissue. There was no observable histological change in apoptosis, or cell number, in response to the alcohol injection. PMID:25097192

Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling

PubMed Central

Darlington, Todd M; McCarthy, Riley D; Cox, Ryan J; Miyamoto-Ditmon, Jill; Gallego, Xavier; Ehringer, Marissa A

2016-01-01

Hedonic substitution, where wheel running reduces voluntary ethanol consumption has been observed in prior studies. Here we replicate and expand on previous work showing that mice decrease voluntary ethanol consumption and preference when given access to a running wheel. While earlier work has been limited mainly to behavioral studies, here we assess the underlying molecular mechanisms that may account for this interaction. From four groups of female C57BL/6J mice (control, access to two-bottle choice ethanol, access to a running wheel, and access to both two-bottle choice ethanol and a running wheel), mRNA-sequencing of the striatum identified differential gene expression. Many genes in ethanol preference quantitative trait loci were differentially expressed due to running. Furthermore, we conducted Weighted Gene Co-expression Network Analysis and identified gene networks corresponding to each effect behavioral group. Candidate genes for mediating the behavioral interaction between ethanol consumption and wheel running include multiple potassium channel genes, Oprm1, Prkcg, Stxbp1, Crhr1, Gabra3, Slc6a13, Stx1b, Pomc, Rassf5, Polr2a, and Camta2. After observing an overlap of many genes and functional groups previously identified in studies of initial sensitivity to ethanol, we hypothesized that wheel running may induce a change in sensitivity, thereby affecting ethanol consumption. A behavioral study examining Loss of Righting Reflex to ethanol following exercise trended toward supporting this hypothesis. These data provide a rich resource for future studies that may better characterize the observed transcriptional changes in gene networks in response to ethanol consumption and wheel running. PMID:27063791

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

PubMed

Jung, U J; Baek, N-I; Chung, H-G; Bang, M-H; Yoo, J-S; Jeong, T S; Lee, K-T; Kang, Y J; Lee, M K; Kim, H J; Yeo, J Y; Choi, M S

2007-10-01

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.

Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain.

PubMed

Zhou, Chunyan; Chen, Jing; Zhang, Xiaolu; Costa, Lucio G; Guizzetti, Marina

2014-11-01

Cholesterol plays a pivotal role in many aspects of brain development; reduced cholesterol levels during brain development, as a consequence of genetic defects in cholesterol biosynthesis, leads to severe brain damage, including microcephaly and mental retardation, both of which are also hallmarks of the fetal alcohol syndrome. We had previously shown that ethanol up-regulates the levels of two cholesterol transporters, ABCA1 (ATP binding cassette-A1) and ABCG1, leading to increased cholesterol efflux and decreased cholesterol content in astrocytes in vitro. In the present study we investigated whether similar effects could be seen in vivo. Pregnant Sprague-Dawley rats were fed liquid diets containing 36% of the calories from ethanol from gestational day (GD) 6 to GD 21. A pair-fed control groups and an ad libitum control group were included in the study. ABCA1 and ABCG1 protein expression and cholesterol and phospholipid levels were measured in the neocortex of female and male fetuses at GD 21. Body weights were decreased in female fetuses as a consequence of ethanol treatments. ABCA1 and ABCG1 protein levels were increased, and cholesterol levels were decreased, in the neocortex of ethanol-exposed female, but not male, fetuses. Levels of phospholipids were unchanged. Control female fetuses fed ad libitum displayed an up-regulation of ABCA1 and a decrease in cholesterol content compared with pair-fed controls, suggesting that a compensatory up-regulation of cholesterol levels may occur during food restriction. Maternal ethanol consumption may affect fetal brain development by increasing cholesterol transporters' expression and reducing brain cholesterol levels. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Neuropeptide Y (NPY) in the central nucleus of the amygdala (CeA) does not affect ethanol-reinforced responding in binge-drinking, nondependent rats.

PubMed

Henderson, Angela N; Czachowski, Cristine L

2012-03-01

The central nucleus of the amygdala (CeA) has been implicated as having a significant role in mediating alcohol-drinking behavior. Neuropeptide Y (NPY) has been investigated as a potential pharmacotherapeutic due to its ability to attenuate ethanol intake, particularly when administered into the CeA. Previous research suggests, though the evidence is somewhat conflicting, that the efficacy of NPY is contingent upon genetic background and/or prior history of ethanol dependence in rats. However, studies looking at the effects of NPY in nonselected animals lacking a history of ethanol dependence have two factors that could impact the interpretation of the results: ethanol history/selection AND relatively low baseline ethanol intakes as compared to ethanol-dependent and/or genetically selected controls. The purpose of the present study was to generate higher baseline ethanol intakes upon which to examine the effects of NPY on ethanol and sucrose drinking in nonselected rats using a binge drinking model. Long Evans rats were trained to complete a single response requirement resulting in access to either 2% sucrose (Sucrose Group) or 2% sucrose/10% ethanol (Ethanol Group) for a 20-min drinking session. On treatment days, rats were bilaterally microinjected into the CeA with aCSF or one of three doses of NPY (0.25μg, 0.50μg, or 1.00μg/.5μL). Subjects in the Ethanol Group were consuming an average of 1.2g/kg of ethanol (yielding BELs of ~90mg%) during the 20min access period following aCSF treatments. The results revealed that NPY had no effect on either sucrose or ethanol consumption or on appetitive responding (latency to respond). Overall, the findings indicate that even a history of binge-like ethanol consumption is not sufficient to recruit CeA NPY activity, and are consistent with previous studies showing that the role of NPY in regulating ethanol reinforcement in the CeA may be contingent upon a prior history of ethanol dependence. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparative Hepatoprotective Activity of Ethanolic Extracts of Cuscuta australis against Acetaminophen Intoxication in Wistar Rats.

PubMed

Folarin, Rachael O; Omirinde, Jamiu O; Bejide, Ronald; Isola, Tajudeen O; Usende, Levi I; Basiru, Afisu

2014-01-01

This study investigates the comparative hepatoprotective activity of crude ethanol extracts of Cuscuta australis against acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed of Cuscuta australis in doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses of Cuscuta australis stem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably, Cuscuta australis (seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions of Cuscuta australis stem appear to protect the liver from acetaminophen intoxication better than the seed counterpart.

Comparative Hepatoprotective Activity of Ethanolic Extracts of Cuscuta australis against Acetaminophen Intoxication in Wistar Rats

PubMed Central

Folarin, Rachael O.; Omirinde, Jamiu O.; Bejide, Ronald; Isola, Tajudeen O.; Usende, Levi I.; Basiru, Afisu

2014-01-01

This study investigates the comparative hepatoprotective activity of crude ethanol extracts of Cuscuta australis against acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed of Cuscuta australis in doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses of Cuscuta australis stem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably, Cuscuta australis (seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions of Cuscuta australis stem appear to protect the liver from acetaminophen intoxication better than the seed counterpart. PMID:27433518

Evaluation of the Shear Bond Strength of Composite Resin to Wet and Dry Enamel Using Dentin Bonding Agents Containing Various Solvents

PubMed Central

Ramarao, Sathyanarayanan; John, Bindu Meera; Rajesh, Praveen; Swatha, S

2017-01-01

Introduction Bonding of composite resin to dentin mandates a wet substrate whereas, enamel should be dry. This may not be easily achievable in intracoronal preparations where enamel and dentin are closely placed to each other. Therefore, Dentin Bonding Agents (DBA) are recommended for enamel and dentinal bonding, where enamel is also left moist. A research question was raised if the “enamel-only” preparations will also benefit from wet enamel bonding and contemporary DBA. Aim The aim of this study was to compare the shear bond strengths of composite resin, bonded to dry and wet enamel using fifth generation DBA (etch and rinse system) containing various solvents such as ethanol/water, acetone and ethanol. Materials and Methods The crowns of 120 maxillary premolars were split into buccal and lingual halves. They were randomly allocated into four groups of DBA: Group 1-water/ethanol based, Group 2-acetone based, Group 3-ethanol based, Group 4-universal bonding agent (control group). The buccal halves and lingual halves were bonded using the wet bonding and dry bonding technique respectively. After application of the DBAs and composite resin build up, shear bond strength testing was done. Results Group 1 (ethanol/water based ESPE 3M, Adper Single Bond) showed highest bond strength of (23.15 MPa) in dry enamel. Group 2 (acetone based Denstply, Prime and Bond NT, showed equal bond strength in wet and dry enamel condition (18.87 MPa and 18.02 MPa respectively). Conclusion Dry enamel bonding and ethanol/water based etch and rinse DBA can be recommended for “enamel-only” tooth preparations. PMID:28274042

An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer

PubMed Central

Daburkar, Mohan; Lohar, Vikram; Rathore, Arvind Singh; Bhutada, Pravin; Tangadpaliwar, Shrikant

2014-01-01

Aim: To examine the preventive effect of Aloe vera gel ethanolic extract using diabetic foot ulcer (DFUs) protocol in Wistar rats. Materials and Methods: Male Wistar rats were divided into untreated control (Group I), untreated DFUs (Group II), DFUs treated with A. vera gel ethanolic extract (Group III), DFUs treated with topical A. vera gel (Group IV), DFUs treated with A. vera gel ethanolic extract and topical A. vera gel (Group V). The rats in the treatment groups were daily administered the A. vera gel and ethanolic extract for 9 days. Fasting blood glucose levels and percentage of wound ulcer contraction were measured on day 3, 6, and 9. Statistical Analysis used: The results are expressed as a mean ± Standard Error Mean (SEM). Data were analyzed using one-way analysis of variance (ANOVA) after Newman–Keuls test. P < 0.05 were considered statistically significant in all cases. Results: Oral administration of A. vera gel ethanolic extract at a dose of 300 mg/kg body weight per day to diabetic rats for a period of 9 days resulted in a significant reduction in fasting blood glucose and a significant improvement in plasma insulin. Topical application of A. vera gel at a dose 30 mg/kg body weight per day to streptozotocin (STZ)-induced diabetic rats for a period of 9 days resulted in no change in blood glucose and plasma insulin. Oral administration as well as topical application of A. vera gel ethanolic extract and gel significantly reduced the blood glucose, improved the plasma insulin, and significantly increased DNA and glycosaminoglycans (GAGs) to improve the wound ulcer healing as well as the breaking strength on day 9. Conclusions: Present findings provide a scientific rationale for the use of A. vera gel ethanolic extract, and showed that the gel attenuated the diabetic foot wound in rats. PMID:25035641

The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

PubMed

Al-Wajeeh, Nahla Saeed; Hajerezaie, Maryam; Noor, Suzita Mohd; Halabi, Mohammed Farouq; Al-Henhena, Nawal; Azizan, Ainnul Hamidah Syahadah; Kamran, Sareh; Hassandarvish, Pouya; Shwter, Abdrabuh N; Karimian, Hamed; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

2017-01-19

Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities. Rats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute toxicity, the liver and kidney revealed no hepatotoxic or nephrotoxic effects histologically. The gastric cytoprotective action of C. barometz hair extract might be attributed to antioxidants, an increase in gastric pH, stomach mucus preservation, increased endogenous antioxidant enzymes, decreased lipid peroxidation, up-regulation of HSP70 and down-regulation of Bax proteins.

Developmental lead exposure induces opposite effects on ethanol intake and locomotion in response to central vs. systemic cyanamide administration.

PubMed

Mattalloni, Mara Soledad; Deza-Ponzio, Romina; Albrecht, Paula Alejandra; Cancela, Liliana Marina; Virgolini, Miriam Beatriz

2017-02-01

Lead (Pb) is a developmental neurotoxicant that elicits differential responses to drugs of abuse. Particularly, ethanol consumption has been demonstrated to be increased as a consequence of environmental Pb exposure, with catalase (CAT) and brain acetaldehyde (ACD, the first metabolite of ethanol) playing a role. The present study sought to interfere with ethanol metabolism by inhibiting ALDH2 (mitochondrial aldehyde dehydrogenase) activity in both liver and brain from control and Pb-exposed rats as a strategy to accumulate ACD, a substance that plays a major role in the drug's reinforcing and/or aversive effects. To evaluate the impact on a 2-h chronic voluntary ethanol intake test, developmentally Pb-exposed and control rats were administered with cyanamide (CY, an ALDH inhibitor) either systemically or intracerebroventricularly (i.c.v.) on the last 4 sessions of the experiment. Furthermore, on the last session and after locomotor activity was assessed, all animals were sacrificed to obtain brain and liver samples for ALDH2 and CAT activity determination. Systemic CY administration reduced the elevated ethanol intake already reported in the Pb-exposed animals (but not in the controls) accompanied by liver (but not brain) ALDH2 inactivation. On the other hand, a 0.3 mg i.c.v. CY administration enhanced both ethanol intake and locomotor activity accompanied by brain ALDH2 inactivation in control animals, while an increase in ethanol consumption was also observed in the Pb-exposed group, although in the absence of brain ALDH2 blockade. No changes were observed in CAT activity as a consequence of CY administration. These results support the participation of liver and brain ACD in ethanol intake and locomotor activity, responses that are modulated by developmental Pb exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Protective effect of N-acetylcysteine against ethanol-induced gastric ulcer: A pharmacological assessment in mice

PubMed Central

Jaccob, Ausama Ayoob

2015-01-01

Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-acetylcysteine (NAC) against ethanol-induced gastric ulcer models in mice. Materials and Methods: A total of 41 mice were allocated into six groups consisted of 7 mice each. Groups 1 (normal control) and 2 (ulcer control) received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg). All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg) was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by anti-secretory, cytoprotective, histological and biochemical data, but the molecular mechanisms behind such protection are complex. PMID:26401392

Mode of oxygen and carbon dioxide action on strawberry ester biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ke, D.; Zhou, L.; Kader, A.A.

1994-09-01

Chandler strawberries (Fragaria ananassa Duck.) were kept in air, 0.25% O[sub 2], 21% O[sub 2] + 50% CO[sub 2], or 0.25 O[sub 2] + 50% CO[sub 2] (balance N[sub 2]) at 5 C for 1 to 7 days to study the effects of controlled atmospheres (CAs) on volatiles and fermentation enzymes. Concentrations of acetaldehyde, ethanol, ethyl acetate, and ethyl butyrate were greatly increased, while concentrations of isopropyl acetate, propyl acetate, and butyl acetate were reduced by the three CA treatments compared to those of air-control fruit. The CA treatments enhanced activities of pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) butmore » slightly decreased activity of alcohol acetyltransferase (AAT). The results indicate that the enhanced PDC and ADH activities by CA treatments cause ethanol accumulation, which in turn drives the biosynthesis of ethyl esters. The increased ethanol concentration also competes with other alcohols for carboxyl groups for esterification reactions. The reduced AAT activity and limited availability of carboxyl groups due to ethanol competition decrease production of other acetate esters.« less

Regulation of ethanol intake under chronic mild stress: roles of dopamine receptors and transporters.

PubMed

Delis, Foteini; Rombola, Christina; Bellezza, Robert; Rosko, Lauren; Grandy, David K; Volkow, Nora D; Thanos, Panayotis K

2015-01-01

Studies have shown that exposure to chronic mild stress decreases ethanol intake and preference in dopamine D2 receptor wild-type mice (Drd2 (+/+)), while it increases intake in heterozygous (Drd2 (+/-)) and knockout (Drd2 (-/-)) mice. Dopaminergic neurotransmission in the basal forebrain plays a major role in the reinforcing actions of ethanol as well as in brain responses to stress. In order to identify neurochemical changes associated with the regulation of ethanol intake, we used in vitro receptor autoradiography to measure the levels and distribution of dopamine D1 and D2 receptors and dopamine transporters (DAT). Receptor levels were measured in the basal forebrain of Drd2 (+/+), Drd2 (+/-), and Drd2 (-/-) mice belonging to one of four groups: control (C), ethanol intake (E), chronic mild stress exposure (S), and ethanol intake under chronic mild stress (ES). D2 receptor levels were higher in the lateral and medial striatum of Drd2 (+/+) ES mice, compared with Drd2 (+/+) E mice. Ethanol intake in Drd2 (+/+) mice was negatively correlated with striatal D2 receptor levels. D2 receptor levels in Drd2(+/-) mice were the same among the four treatment groups. DAT levels were lower in Drd2(+/-) C and Drd2 (-/-) C mice, compared with Drd2 (+/+) C mice. Among Drd2(+/-) mice, S and ES groups had higher DAT levels compared with C and E groups in most regions examined. In Drd2(-/-) mice, ethanol intake was positively correlated with DAT levels in all regions studied. D1 receptor levels were lower in Drd2(+/-) and Drd2(-/-) mice, compared with Drd2(+/+), in all regions examined and remained unaffected by all treatments. The results suggest that in normal mice, ethanol intake is associated with D2 receptor-mediated neurotransmission, which exerts a protective effect against ethanol overconsumption under stress. In mice with low Drd2 expression, where DRD2 levels are not further modulated, ethanol intake is associated with DAT function which is upregulated under stress leading to ethanol overconsumption.

Conformational Changes of the Alanine Dipeptide in Water-Ethanol Binary Mixtures.

PubMed

Almeida, Glauco G; Cordeiro, João M M; Martín, M Elena; Aguilar, Manuel A

2016-04-12

Experimental work developed in the last years has evidenced the capacity of alcohols and polyalcohols to modify the energy landscape of peptides and proteins. However, the mechanism underlying this effect is not clear. Taking as a model system the alanine dipeptide (AD) we perform a QM/MM study in water, ethanol, and a 40-60% in volume water-ethanol mixture. The AD molecule was described at the MP2/aug-cc-pVDZ level. In polar solution, only αR and PPII conformers contribute in an appreciable way to the conformational equilibrium. The final in solution αR-PPII free energy difference is determined from the interplay between the internal energy of the dipeptide and the solute-solvent interaction free energy. Internal energy favors the formation of PPII, whereas, on the contrary, solute-solvent interaction is favorable to αR, so any factor that decreases the solute-solvent interaction free energy will increase the PPII population. The addition of ethanol increases the stability of the PPII conformer. Our results point to the presence of preferential solvation in this system, the composition of the first solvation shell in the binary mixture being dominated by water molecules. Remarkably, this fact does not affect the differential conformational stability that is controlled by long-range interactions. From the analysis of solvent density maps it is concluded that, in the water-ethanol mixture, ethanol molecules are more likely found around the alanine side chain and the carbonyl group, but while in PPII ethanol molecules interact mainly with the carbonyl group of the N-terminal end, in C5 the interaction is with the carbonyl group of the C-terminal end. In αR, ethanol interacts with both carbonyl groups.

Effects of aqueous extracts from Panax ginseng and Hippophae rhamnoides on acute alcohol intoxication: An experimental study using mouse model.

PubMed

Wen, Da-Chao; Hu, Xiao-Yu; Wang, Yan-Yan; Luo, Jian-Xing; Lin, Wu; Jia, Ling-Yan; Gong, Xin-Yue

2016-11-04

Acute alcohol intoxication (AAI) is a frequent emergency, but therapeutic drugs with superior efficacy and safety are lacking. Panax ginseng (PG) and Hippophae rhamnoides (HR) respectively has a wide application as a complementary therapeutic agent in China for the treatment of AAI and liver injury induced by alcohol. We investigated the effects of aqueous extracts from PG and HR (AEPH) on AAI mice and identified its underlying mechanisms. Models of AAI were induced by intragastric administration of ethanol (8g/kg). Seventy-two Specific pathogen-free (SPF) male Kunming mice were randomly divided into six groups: normal group, positive control group, AEPH of low dosage (100mg/kg) group, AEPH of medium dose (200mg/kg) group, AEPH of high dosage (400mg/kg) group and model group. The mice were treated with metadoxine (MTD, 500mg/kg) and AEPH. Thirty minutes later, the normal group was given normal saline, while the other groups were given ethanol (i.g., 8g/kg). The impact of AEPH was observed. In the same way, another seventy-two Kunming mice were randomly divided into six groups equally. The blood ethanol concentration at 0.5, 1, 1.5, 2, 3 and 6h after ethanol intake was determined by way of gas chromatography. The activity of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal ethanol oxidase (EO) in liver, and the concentration of β-endorphin (β-EP), leucine-enkephalin (LENK) in the brain were determined by enzyme-linked-immunosorbent serologic assay (ELISA). AEPH markedly prolonged alcohol tolerance time and shortened sober-up time after acute ethanol administration. AEPH decreased blood ethanol levels in six tests after ethanol intake. The 7-day survival rate of AEPH group was obviously superior to model group. AEPH increased the activities of ADH, ALDH, and decreased EO activity in liver. The crucial find was that AEPH markedly decreased β-EP and LENK concentration in the brain. AEPH can markedly increase the levels of ADH, ALDH, decrease EO activity in liver and decrease the concentration of β-EP and LENK in the brain to against acute alcohol intoxication in mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

PubMed Central

Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

2011-01-01

Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in 2-AG biosynthesis (e.g. DAGL-α/β) were found in any condition. Conclusions These findings suggest that ethanol dependence and withdrawal are associated with dysregulated endocannabinoid signaling in the amygdala. These alterations may contribute to withdrawal-related dysregulation of amygdalar neurotransmission. PMID:22141465

Protective effect of ethanolic extract of polyherbal formulation on carbon tetrachloride induced liver injury

PubMed Central

Gurusamy, K; Kokilavani, R; Arumugasamy, K; Sowmia, C

2009-01-01

Protective effect of ethanolic extract of polyherbalformulation (PHF) of three medicinalplants was studied on carbon tetrachloride induced liver damage in rats. Treatment with 250mg I kg b.w. of ethanolic extract of PHF protected rats against carbon tetrachloride liver injury by significantly lowering 5’NT, GGF, GDH and SDH and bilirubin levels compared to control group of rats. Normalising the effect of these parameters indicates strong hepatoprotective property of the PHF extract. PMID:22557313

Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism

PubMed Central

Kosaraju, Jayasankar; Chinni, Santhivardhan; Roy, Partha Deb; Kannan, Elango; Antony, A. Shanish; Kumar, M. N. Satish

2014-01-01

Objective: The present study investigates the neuroprotective activity of ethanol extract of Tinospora cordifolia aerial parts against 6-hydroxy dopamine (6-OHDA) lesion rat model of Parkinson's disease (PD). Materials and Methods: T. cordifolia ethanol extract (TCEE) was standardized with high performance thin layer chromatography using berberine. Experimental PD was induced by intracerebral injection of 6-OHDA (8 μg). Animals were divided into five groups: sham operated, negative control, positive control (levodopa 6 mg/kg) and two experimental groups (n = 6/group). Experimental groups received 200 and 400 mg/kg of TCEE once daily for 30 days by oral gavage. Biochemical parameters including dopamine level, oxidative stress, complex I activity and brain iron asymmetry ratio and locomotor activity including skeletal muscle co-ordination and degree of catatonia were assessed. Results: TCEE exhibited significant neuroprotection by increasing the dopamine levels (1.96 ± 0.20 and 2.45 ± 0.40 ng/mg of protein) and complex I activity (77.14 ± 0.89 and 78.50 ± 0.96 nmol/min/mg of protein) at 200 and 400 mg/kg respectively when compared with negative control group. Iron asymmetry ratio was also significantly attenuated by TCEE at 200 (1.57 ± 0.18) and 400 mg/kg (1.11 ± 0.15) when compared with negative control group. Neuroprotection by TCEE was further supported by reduced oxidative stress and restored locomotor activity in treatment groups. Conclusion: Results show that TCEE possess significant neuroprotection in 6-OHDA induced PD by protecting dopaminergic neurons and reducing the iron accumulation. PMID:24741189

Prenatal ethanol exposure alters steroidogenic enzyme activity in newborn rat testes.

PubMed

Kelce, W R; Rudeen, P K; Ganjam, V K

1989-10-01

We have examined the in utero effects of ethanol exposure on testicular steroidogenesis in newborn male pups. Pregnant Sprague-Dawley rats were fed a liquid ethanol diet (35% ethanol-derived calories), a pair-fed isocaloric liquid diet, or a standard laboratory rat chow and water diet beginning on Day 12 of gestation and continuing through parturition. Although there were no significant differences in the enzymatic activity of 5-ene-3 beta-hydroxysteroid dehydrogenase/isomerase or C17,20-lyase, the enzymatic activity of 17 alpha-hydroxylase was significantly (p less than 0.01) reduced (i.e., approximately 36%) in the ethanol-exposed pups compared to those from the pair-fed and chow treatment groups. This lesion in testicular steroidogenic enzyme activity in newborn male pups exposed to alcohol in utero was transient as 17 alpha-hydroxylase activity from the ethanol-exposed animals returned to control levels by postnatal Day 20 and remained at control levels through adulthood (postnatal Day 60). These data suggest that the suppression of the perinatal testosterone surge in male rats exposed to alcohol in utero and the associated long term demasculinizing effects of prenatal ethanol exposure might be the result of reduced testicular steroidogenic enzyme activity in the perinatal animal.

Ethanol affects hepatitis C pathogenesis: humanized SCID Alb-uPA mouse model.

PubMed

Osna, Natalia A; Kharbanda, Kusum K; Sun, Yimin; Simpson, Ronda L; Poluektova, Larisa E; Ganesan, Murali; Wisecarver, James L; Mercer, David F

2014-07-18

Alcohol consumption exacerbates the course of hepatitis C viral (HCV) infection, worsens outcomes and contributes to the development of chronic infection that exhibits low anti-viral treatment efficiency. The lack of suitable in vivo models makes HCV-ethanol studies very difficult. Here, we examine whether chimeric SCID Alb-uPA mice transplanted with human hepatocytes and infected with HCV develop worsening pathology when fed ethanol. After 5 weeks of feeding, such mice fed chow+water (control) or chow+20% ethanol in water (EtOH) diets mice developed oxidative stress, decreased proteasome activity and increased steatosis. Importantly, HCV(+) mice in the control group cleared HCV RNA after 5 weeks, while the infection persisted in EtOH-fed mice at the same or even higher levels compared with pre-feeding HCV RNA. We conclude that in chimeric SCID Alb-uPA mice, EtOH exposure causes the complex biochemical and histological changes typical for alcoholic liver injury. In addition, ethanol feeding delays the clearance of HCV RNA thereby generating persistent infection and promoting liver injury. Overall, this model is appropriate for conducting HCV-ethanol studies. Published by Elsevier Inc.

Chronic moderate alcohol drinking alters insulin release without affecting cognitive and emotion-like behaviors in rats.

PubMed

Nelson, Nnamdi G; Suhaidi, Faten A; Law, Wen Xuan; Liang, Nu-Chu

2017-12-16

Because the consumption of alcoholic beverages prevails in society, its effects on diabetes risk is a subject of interest. Extant literature on this issue often disagrees. Here, we probed the effects of chronic moderate ethanol consumption on glucose metabolism in rats. The effect of chronic moderate alcohol drinking on depression- and anxiety-like behaviors and memory was also explored. Adolescent male and female Long-Evans rats consumed saccharin-sweetened 5% (1 week) and 10% ethanol (7 weeks) under a 7.5-h/day (Monday-Friday) access schedule. This exposure was followed by sucrose preference and elevated plus maze (EPM) tests during an intervening week, before a 6-week intermittent-access (Monday, Wednesday, Friday) to 20% unsweetened ethanol in a 2-bottle choice drinking paradigm was implemented (EtOH). A free-feeding control group received water (Water). Our prior work revealed that voluntary ethanol consumption decreases food intake in rats. Hence, a second control group that received water was mildly food-restricted (FR), and their average body weight was matched to that of the EtOH group. During the week following week 6 of intermittent-access to 20% ethanol, rats were submitted to sucrose preference, EPM, and novel object recognition (NOR) tests. Insulin response to a glucose load was subsequently assessed via an oral glucose tolerance test (OGTT). Rats attained and maintained blood ethanol concentrations of ∼55 mg/dL that correlated with the dose of sweetened 10% ethanol ingested. Relative to intake by Water controls, EtOH rats consumed less chow. There was no body weight difference between both groups. Neither sex of EtOH rats showed increased depression- and anxiety-like behaviors, as respectively measured by sucrose preference and EPM, nor did they show deficit in object recognition memory during abstinence. Male EtOH rats, however, showed signs of reduced general activity on the EPM. During OGTT, male EtOH rats showed a time-dependent potentiation of insulin release for proper glucose clearance. Such an effect was not observed in females. This landmark study shows that chronic moderate alcohol consumption can have negative metabolic consequences in the absence of overt behavioral deficits, especially in males. Published by Elsevier Inc.

Anti-Inflammatory Activity of Pinus koraiensis Cone Bark Extracts Prepared by Micro-Wave Assisted Extraction

PubMed Central

Kang, Sun-Ae; Kim, Dong-Hee; Hong, Shin-Hyub; Park, Hye-Jin; Kim, Na-Hyun; Ahn, Dong-Hyun; An, Bong-Jeun; Kwon, Joong-Ho; Cho, Young-Je

2016-01-01

In this study, we compared the anti-inflammatory activity of Pinus koraiensis cone bark extracts prepared by conventional extraction and microwave-assisted extraction (MAE). Water extracts and 50% ethanol extracts prepared using MAE were applied to RAW 264.7 cell at 5, 10, 25, and 50 μg/mL of concentrations, and tested for cytoxicity. The group treated with 50 μg/mL of 50% ethanol extracts showed toxicity. In order to investigate the inhibition of nitric oxide (NO) production in RAW 264.7 cells, extracts of water and ethanol were treated with 5, 10, and 25 μg/mL concentrations. The inhibitory activity of water and 50% ethanol extracts groups were determined as 40% and 60% at 25 μg/mL concentration, respectively. We found concentration dependent decreases on inducible NO synthase. The inhibitory effect against forming inflammatory cytokines, prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β, was also superior in the 25 μg/mL treated group than the control group. According to these results, the water extracts and 50% ethanol extracts both inhibited inflammatory mediators by reducing the inflammatory response. Therefore, The MAE extracts of P. koraiensis cone bark can be developed as a functional ingredient with anti-inflammatory activity. PMID:27752500

Autoshaping of ethanol drinking in rats: effects of ethanol concentration and trial spacing.

PubMed

Tomie, Arthur; Wong, Karlvin; Apor, Khristine; Patterson-Buckendahl, Patricia; Pohorecky, Larissa A

2003-11-01

In two studies, we evaluated the effects of ethanol concentration and trial spacing on Pavlovian autoshaping of ethanol drinking in rats. In these studies, the brief insertion of an ethanol sipper conditioned stimulus (CS) was followed by the response-independent presentation of food unconditioned stimulus (US), inducing sipper CS-directed drinking conditioned responses (CRs) in all rats. In Experiment 1, the ethanol concentration in the sipper CS [0%-16% volume/volume (vol./vol.), in increments of 1%] was systematically increased within subjects across autoshaping sessions. Groups of rats received sipper CS-food US pairings (Paired/Ethanol), a CS-US random procedure (Random/Ethanol), or water sipper CS paired with food US (Paired/Water). In Experiment 2, saccharin-fading procedures were used to initiate, in the Ethanol group, drinking of 6% (vol./vol.) ethanol in 0.1% saccharin or, in the Water group, drinking of tap water in 0.1% saccharin. After elimination of saccharin, and across days, the duration of access to the sipper CS during each autoshaping trial was increased (5, 10, 12.5, 15, 17.5, and 20 s), and subsequently, across days, the duration of the mean intertrial interval (ITI) was increased (60, 90, 120, and 150 s). In Experiment 1, Paired/Ethanol and Random/Ethanol groups showed higher intake of ethanol, in terms of grams per kilogram of body weight, at higher ethanol concentrations, with more ethanol intake recorded in the Paired/Ethanol group. In Experiment 2, the Ethanol group drank more than was consumed by the Water group, and, for both groups, fluid intake increased with longer ITIs. Results support the suggestion that autoshaping contributes to sipper CS-directed ethanol drinking.

Effects of Soy Protein Hydrolysates Prepared by Varying Subcritical Media on the Physicochemical Properties of Pork Patties

PubMed Central

Davaatseren, Munkhtugs

2016-01-01

This study investigated the effect of soy protein hydrolysates (SPH) prepared by varying subcritical media on the physicochemical properties of pork patties. For resource of SPH, two different soybean species (Glycine max Merr.) of Daewonkong (DWK) and Saedanbaek (SDB) were selected. SPH was prepared by subcritical processing at 190℃ and 25 MPa under three different of media (water, 20% ethanol and 50% ethanol). Solubility and free amino group content revealed that water was better to yield larger amount of SPH than ethanol/water mixtures, regardless of species. Molecular weight (Mw) distribution of SPH was also similar between two species, while slightly different Mw distribution was obtained by subcritical media. For pork patty application, 50% ethanol treatment showed clear red color comparing to control after 14 d of storage. In addition, ethanol treatment had better oxidative stability than control and water treatment based on thiobarbituric acid-reactive substances (TBARS) analysis. For eating quality, although 20% ethanol treatment in SDB showed slightly higher cooking loss than control, generally addition of SPH did not affect the water-binding properties and hardness of pork patties. Consequently, the present study indicated that 50% ethanol was the best subcritical media to produce SPH possessing antioxidant activity, and the SPH produced from DWK exhibited better antioxidant activity than that produced SDB. PMID:27499657

Effects of Soy Protein Hydrolysates Prepared by Varying Subcritical Media on the Physicochemical Properties of Pork Patties.

PubMed

Lee, Yun-Kyung; Ko, Bo-Bae; Davaatseren, Munkhtugs; Hong, Geun-Pyo

2016-01-01

This study investigated the effect of soy protein hydrolysates (SPH) prepared by varying subcritical media on the physicochemical properties of pork patties. For resource of SPH, two different soybean species (Glycine max Merr.) of Daewonkong (DWK) and Saedanbaek (SDB) were selected. SPH was prepared by subcritical processing at 190℃ and 25 MPa under three different of media (water, 20% ethanol and 50% ethanol). Solubility and free amino group content revealed that water was better to yield larger amount of SPH than ethanol/water mixtures, regardless of species. Molecular weight (Mw) distribution of SPH was also similar between two species, while slightly different Mw distribution was obtained by subcritical media. For pork patty application, 50% ethanol treatment showed clear red color comparing to control after 14 d of storage. In addition, ethanol treatment had better oxidative stability than control and water treatment based on thiobarbituric acid-reactive substances (TBARS) analysis. For eating quality, although 20% ethanol treatment in SDB showed slightly higher cooking loss than control, generally addition of SPH did not affect the water-binding properties and hardness of pork patties. Consequently, the present study indicated that 50% ethanol was the best subcritical media to produce SPH possessing antioxidant activity, and the SPH produced from DWK exhibited better antioxidant activity than that produced SDB.

Effects of ethanolic extract of Jasminum grandiflorum Linn. flowers on wound healing in diabetic Wistar albino rats

PubMed Central

Hirapara, Hiren; Ghori, Vishal; Anovadiya, Ashish; Baxi, Seema; Tripathi, Chandrabhanu

2017-01-01

Objective: To evaluate wound healing activity of ethanolic extract of Jasminum grandiflorum Linn. (J. grandiflorum) flowers in diabetic rats. Materials and Methods: Streptozotocin-induced diabetic Wistar albino rats were divided into six groups (n=6).Three groups – diabetic control, positive control (that received Glibenclamide) and treatment (that received J. grandiflorum Linn. Flower extract) were operated for excision wounds (EW). These groups were evaluated for wound contraction and re-epithelization. The other three groups were operated for incision wounds (IW) and dead space wounds (DW). Incision and dead space wounds were produced in the same rats. IWs were analyzed for wound breaking strength and the granulation tissues from DWs were analyzed for dry weight, hydroxyproline content, and histology. Results: IWs and DWs showed significant improvement in wound breaking strength (265.8±10.4 vs 332.5±8.2; p<0.05), granulation tissue dry weight (26.1±0.6vs 40.4±0.3; p<0.01) and hydroxyproline content (19.3±0.5 vs 32.6±0.8; p<0.01) in treatment group as compared to control group. Neo-angiogenesis was also high in treatment group. Wound contraction was earlier (day 14) in treatment group compared to diabetic control (day 20). No significant improvement was seen in re-epithelization in treatment group. Conclusion: Ethanolic extract of J. grandiflorum Linn. flowers increases granulation tissue formation as well as neo-angiogenesis. It also enhances wound contraction; however, re-epithelization was not significantly affected. J. grandiflorum Linn. flowers could be potentially effective in promotion of diabetic wounds healing by increasing granulation tissue formation and enhancing wound contraction; however, further studies are required for its clinical application. PMID:29062801

Effects of ethanolic extract of Jasminum grandiflorum Linn. flowers on wound healing in diabetic Wistar albino rats.

PubMed

Hirapara, Hiren; Ghori, Vishal; Anovadiya, Ashish; Baxi, Seema; Tripathi, Chandrabhanu

2017-01-01

To evaluate wound healing activity of ethanolic extract of Jasminum grandiflorum Linn. ( J. grandiflorum ) flowers in diabetic rats. Streptozotocin-induced diabetic Wistar albino rats were divided into six groups (n=6).Three groups - diabetic control, positive control (that received Glibenclamide) and treatment (that received J. grandiflorum Linn. Flower extract) were operated for excision wounds (EW). These groups were evaluated for wound contraction and re-epithelization. The other three groups were operated for incision wounds (IW) and dead space wounds (DW). Incision and dead space wounds were produced in the same rats. IWs were analyzed for wound breaking strength and the granulation tissues from DWs were analyzed for dry weight, hydroxyproline content, and histology. IWs and DWs showed significant improvement in wound breaking strength (265.8±10.4 vs 332.5±8.2; p<0.05), granulation tissue dry weight (26.1±0.6vs 40.4±0.3; p<0.01) and hydroxyproline content (19.3±0.5 vs 32.6±0.8; p<0.01) in treatment group as compared to control group. Neo-angiogenesis was also high in treatment group. Wound contraction was earlier (day 14) in treatment group compared to diabetic control (day 20). No significant improvement was seen in re-epithelization in treatment group. Ethanolic extract of J. grandiflorum Linn. flowers increases granulation tissue formation as well as neo-angiogenesis. It also enhances wound contraction; however, re-epithelization was not significantly affected. J. grandiflorum Linn. flowers could be potentially effective in promotion of diabetic wounds healing by increasing granulation tissue formation and enhancing wound contraction; however, further studies are required for its clinical application.

Reduction of alcohol induced sleep time in albino mice by potentized Nux vomica prepared with 90% ethanol.

PubMed

Sukul, A; Sinhabau, S P; Sukul, N C

1999-04-01

Male adult albino mice were administered potentized Nux vomica 30 c (Nux v). The drug was mixed with sterile distilled water at 0.05 ml/2 ml water and given at 0.05 ml/individual. Control consisted of blank ethanol solution. Ethanolic extract from the seeds of Strychnos nuxvomica L was mixed with 90% ethanol 1:100 and sonicated for 30 s at 20 KHz. This was further diluted and sonicated in 30 steps to produce Nux v 30 c. Six hours after treatment, mice were given 25% ethanol i.p. at 4 g/kg body wt. The duration of sleep time starting from the loss of righting reflex until its restoration was recorded for each mouse. The duration of sleep time with ethanol was recorded in four sessions for the same group of mice with an interval of 10 d between sessions. session 1 with control solution, 2 with Nux v (oral), 3 with control solution and 4 with Nux v (i.p.). Nux v (oral) produced the shortest sleep time as compared to other treatments which did not differ from each other significantly with respect to sleep time. In another experiment Nux v 30 c was prepared with distilled water and pure absolute ethanol by the above process of successive dilution and sonication. These two preparations together with Nux v 30 c, prepared with 90% ethanol, were tested on mice for their effect on alcohol-induced sleep time. Only Nux v 30 c prepared with 90% ethanol was effective in reducing the sleep time in mice. It is concluded that the solution structure of ethanol/water mixture carries the specificity of the Nux v at ultra high dilution. It is further concluded that the effect is mediated through oral receptors.

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice

PubMed Central

Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan

2016-01-01

AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. METHODS: The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. RESULTS: DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 mRNA in pancreas decreased, but TIMP-1 mRNA increased at model group. CONCLUSION: DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis. PMID:26973392

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.

PubMed

Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan

2016-03-14

To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 mRNA in pancreas decreased, but TIMP-1 mRNA increased at model group. DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis.

Antidiabetic, antihyperlipidemic, and antioxidant activities of Musa balbisiana Colla. in Type 1 diabetic rats.

PubMed

Borah, Mukundam; Das, Swarnamoni

2017-01-01

To evaluate the antidiabetic, antihyperlipidemic, and antioxidant activities of the ethanolic extracts of the flowers and inflorescence stalk of Musa balbisiana Colla. in streptozotocin (STZ)-induced Type 1 diabetic rats. Diabetes was induced in male Wistar albino rats (150-200 g) by single intraperitoneal injection of STZ (60 mg/kg b.w. i.p.). Albino rats ( n = 25) were divided into five groups, of which five animals each. Group A (normal control) and Group B (diabetic control) received normal saline (10 ml/kg/day p.o.), whereas Group C and Group D received 250 mg/kg/day p.o. of flower and inflorescence stalk ethanolic extracts, respectively, for 2 weeks. Group E (diabetic standard) received 6 U/kg/day s.c of Neutral Protamine Hagedorn insulin. Fasting blood sugar, serum insulin, catalase (CAT), malondialdehyde (MDA), and serum lipid profile were estimated at specific intervals of time. Effect of the extracts on intestinal glucose absorption was also evaluated to know the probable mechanism of action. Diabetic control exhibited significant increase in blood glucose, serum cholesterol, triglycerides, low-density lipoprotein, serum MDA levels and decreased serum CAT, and high-density lipoprotein levels which were significantly reverted by flower and inflorescence stalk ethanolic extracts after 2 weeks. Serum insulin levels were in increased ( P < 0.05), and intestinal glucose absorption decreased significantly ( P < 0.01) in extract-treated groups. Flower and inflorescence stalk of M. balbisiana Colla. possess significant antidiabetic, antihyperlipidemic, and antioxidant activities in STZ-induced Type 1 diabetic rats.

Sweetened ethanol drinking during social isolation: enhanced intake, resistance to genetic heterogeneity and the emergence of a distinctive drinking pattern in adolescent mice.

PubMed

Panksepp, J B; Rodriguez, E D; Ryabinin, A E

2017-03-01

With its ease of availability during adolescence, sweetened ethanol ('alcopops') is consumed within many contexts. We asked here whether genetically based differences in social motivation are associated with how the adolescent social environment impacts voluntary ethanol intake. Mice with previously described differences in sociability (BALB/cJ, C57BL/6J, FVB/NJ and MSM/MsJ strains) were weaned into isolation or same-sex pairs (postnatal day, PD, 21), and then given continuous access to two fluids on PDs 34-45: one containing water and the other containing an ascending series of saccharin-sweetened ethanol (3-6-10%). Prior to the introduction of ethanol (PDs 30-33), increased water and food intake was detected in some of the isolation-reared groups, and controls indicated that isolated mice also consumed more 'saccharin-only' solution. Voluntary drinking of 'ethanol-only' was also higher in a subset of the isolated groups on PDs 46-49. However, sweetened ethanol intake was increased in all isolated strain × sex combinations irrespective of genotype. Surprisingly, blood ethanol concentration (BEC) was not different between these isolate and socially housed groups 4 h into the dark phase. Using lickometer-based measures of intake in FVB mice, we identified that a predominance of increased drinking during isolation transpired outside of the typical circadian consumption peak, occurring ≈8.5 h into the dark phase, with an associated difference in BEC. These findings collectively indicate that isolate housing leads to increased consumption of rewarding substances in adolescent mice independent of their genotype, and that for ethanol this may be because of when individuals drink during the circadian cycle. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in rats.

PubMed

Chu, I; Poon, R; Valli, V; Yagminas, A; Bowers, W J; Seegal, R; Vincent, R

2005-01-01

The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin-O-deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol-gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible biochemical hematological and histological effects, with some indications of interactions when they were co-administered.

Running increases ethanol preference.

PubMed

Werme, Martin; Lindholm, Sara; Thorén, Peter; Franck, Johan; Brené, Stefan

2002-07-18

Wheel running performed by rats is reinforcing, rewarding and possibly addictive. In this study we analyzed if wheel running could affect ethanol preference. Lewis rats, known to be both addiction-prone and to develop an excessive wheel running behavior, were given access to ethanol in a two-bottle free-choice paradigm. The animals reached a high and stable ethanol intake after 5 weeks. In the next phase, rats were subjected to ethanol withdrawal for 1, 2 or 4 weeks with or without access to running wheels. Finally animals were again given access to ethanol in the same two-bottle free-choice paradigm, combined with access to running wheels. The rats that ran in running wheels during 1 or 2, but not 4, weeks of ethanol withdrawal increased both ethanol intake and preference as compared with the control group that did not have access to the wheels. Previous studies have demonstrated that low doses of morphine increases ethanol preference. Here we show that also running potentiates ethanol intake and preference. Thus, running which shares many of the reinforcing properties with addictive drugs appears to potentiate rats to an increased preference for ethanol. Our results describe a behavioral interaction where running increases ethanol consumption.

The immunomodulatory effect of Zingiber cassumunar ethanolic extract on phagocytic activity, nitrit oxide and reaxtive oxygen intermediate secretions of macrophage in mice

NASA Astrophysics Data System (ADS)

Nurkhasanah; Santoso, R. D.; Fauziah, R.

2017-11-01

Immunomodulators could protect the body from a variety of infectious agents and boost immunity. Zingiber cassumunar rhizome or bangle potentially showed as an immunomodulator through increasing of macrophage activity in vitro. The objective of the study was to determine the effect of Z. cassumunar rhizome ethanolic extract on phagocytic activity, nitrite oxide (NO) and reactive oxygen intermediate (ROI) secretions in macrophages in vivo. A total of 200 g of Z. cassumunar rhizome was powdered, macerated in 96% ethanol and evaporated to get concentrated extract. Mice were divided into 5 groups as follow: the normal group was given by water only, the negative control group was given by a 0.94% CMC-Na suspension, the treatment groups were given by 250, 500 and 1000 mg/kgBW, respectively, of Z. cassumunar ethanolic extract. The extract was administered orally for 7 days. On the 8th day the mice were injected intraperitoneally 0.7 mg/kg BW of lipopolysaccharide. Four hours later macrophage was isolated. Furthermore, the determination of the phagocytic activity, NO and ROI secretions levels of macrophage were performed. The treatments of 250, 500 and 1000 mg/kg BW of Z. cassumunar ethanolic extract significantly increase the ROI and NO secretions levels (p<0.05), but did not increase the phagocytic activity (p>0.05) of macrophage. Z. cassumunar ethanolic extract have immunomodulatory effect in vivo.

EFFECTS OF ETHANOL EXPOSURE DURING ADOLESCENCE OR IN ADULTHOOD ON PAVLOVIAN CONDITIONED APPROACH IN SPRAGUE-DAWLEY RATS

PubMed Central

McClory, Alexander James; Spear, Linda

2014-01-01

Human studies have shown that adolescents who repeatedly use alcohol are more likely to be dependent on alcohol and are more likely to suffer from psychological problems later in life. There has been limited research examining how ethanol exposure in adolescence might contribute to later abuse or addiction in adulthood. The present experiment examined effects of intermittent ethanol exposure during adolescence on sign-tracking behavior in adulthood, indexed by a Pavlovian conditioned approach (PCA) task wherein an 8-s lever presentation served as a cue predicting subsequent delivery of a flavored food pellet. Although no response was required for food delivery, after multiple pairings, 1 of 2 different responses often emerged during the lever presentation: goal tracking (head entries into the food trough) or sign tracking (engagement with the lever when presented). Sign tracking is thought to reflect the attribution of incentive salience to reward-paired cues and has been previously correlated with addiction-like behaviors. Following the last PCA session, blood samples were collected for analysis of post-session corticosterone levels. Sixty-two rats (n = 10–12/group) were pseudo-randomly assigned to 1 of 2 intragastric (i.g.) exposure groups (water or 4 g/kg ethanol) or a non-manipulated (NM) control group. Animals were intubated with ethanol or water every other session from postnatal session (PND) 28–48 or PND 70–90. Rats were then tested in adulthood (PND 71–79 or PND 113–122) on the PCA task. Animals exposed chronically to ethanol during adolescence exhibited significantly higher levels of sign-tracking behavior in adulthood than NM and water-treated animals, and showed higher corticosterone than NM control animals. These effects were not seen after comparable ethanol exposure in adulthood. These results suggest that adolescent alcohol exposure has long-term consequences on the expression of potential addiction-relevant behaviors in adulthood. PMID:25449366

Effects of ethanol exposure during adolescence or in adulthood on Pavlovian conditioned approach in Sprague-Dawley rats.

PubMed

McClory, Alexander James; Spear, Linda Patia

2014-12-01

Human studies have shown that adolescents who repeatedly use alcohol are more likely to be dependent on alcohol and are more likely to suffer from psychological problems later in life. There has been limited research examining how ethanol exposure in adolescence might contribute to later abuse or addiction in adulthood. The present experiment examined effects of intermittent ethanol exposure during adolescence on sign-tracking behavior in adulthood, indexed by a Pavlovian conditioned approach (PCA) task wherein an 8s lever presentation served as a cue predicting subsequent delivery of a flavored food pellet. Although no response was required for food delivery, after multiple pairings, 1 of 2 different responses often emerged during the lever presentation: goal tracking (head entries into the food trough) or sign tracking (engagement with the lever when presented). Sign tracking is thought to reflect the attribution of incentive salience to reward-paired cues and has been previously correlated with addiction-like behaviors. Following the last PCA session, blood samples were collected for analysis of post-session corticosterone levels. Sixty-two rats (n = 10-12/group) were pseudo-randomly assigned to 1 of 2 intragastric (i.g.) exposure groups (water or 4 g/kg ethanol) or a non-manipulated (NM) control group. Animals were intubated with ethanol or water every other session from postnatal session (PND) 28-48 or PND 70-90. Rats were then tested in adulthood (PND 71-79 or PND 113-122) on the PCA task. Animals exposed chronically to ethanol during adolescence exhibited significantly higher levels of sign-tracking behavior in adulthood than NM and water-treated animals, and showed higher corticosterone than NM control animals. These effects were not seen after comparable ethanol exposure in adulthood. These results suggest that adolescent alcohol exposure has long-term consequences on the expression of potential addiction-relevant behaviors in adulthood. Copyright © 2014 Elsevier Inc. All rights reserved.

Acanthoic acid protectsagainst ethanol-induced liver injury: Possible role of AMPK activation and IRAK4 inhibition.

PubMed

Yao, You-Li; Han, Xin; Song, Jian; Zhang, Jing; Li, Ya-Mei; Lian, Li-Hua; Wu, Yan-Ling; Nan, Ji-Xing

2017-11-05

The aim of this study was to investigate the effects of acanthoic acid (AA) on the regulation of inflammatory response, lipid accumulation, and fibrosis via AMPK- IRAK4 signaling against chronic alcohol consumption in mice. Ethanol-induced liver injury was induced in male mice by Lieber-DeCarli diet for 28d. And mice in AA groups were gavaged with AA (20 or 40mg/kg) for 28d. AA treatment significantly decreased serum AST and TG, hepatic TG levels, serum ethanol and LPS levels compared with chronic ethanol administration. AA ameliorated histological changes, lipid droplets, hepatic fibrosis, and inflammation induced by ethanol. AA significantly increased the expressions of p-LKB1, p-AMPK, and SIRT1 caused by chronic ethanol administration, and attenuated the increasing protein expressions of IRAK1 and IRAK4.siRNA against AMPKα1 blocked AMPKα1 and increased IRAK4 protein expressions, compared with control-siRNA-transfected group, while AA treatment significantly decreased IRAK4 expressions compared with AMPKα1-siRNA-transfected group. AMPK-siRNA also blocked the decreased effect of AA on inflammatory factors. AA decreased over-expression of IRAK4 and inflammation under ethanol plus LPS challenge. AA recruited LKB1-AMPK phosphorylation and activated SIRT1 to regulate alcoholic liver injury, especially, inhibited IRAK1/4 signaling pathway to regulate lipid metabolism, hepatic fibrosis and inflammation caused by alcohol consumption. Copyright © 2017 Elsevier B.V. All rights reserved.

Apoptosis of Purkinje and granular cells of the cerebellum following chronic ethanol intake.

PubMed

Oliveira, Suelen A; Chuffa, Luiz Gustavo A; Fioruci-Fontanelli, Beatriz Aparecida; Lizarte Neto, Fermino Sanches; Novais, Paulo Cezar; Tirapelli, Luiz Fernando; Oishi, Jorge Camargo; Takase, Luiz Fernando; Stefanini, Maira Aparecida; Martinez, Marcelo; Martinez, Francisco Eduardo

2014-12-01

Ethanol alters motricity, learning, cognition, and cellular metabolism in the cerebellum. We evaluated the effect of ethanol on apoptosis in Golgi, Purkinje, and granule cells of the cerebellum in adult rats. There were two groups of 20 rats: a control group that did not consume ethanol and an experimental group of UChA rats that consumed ethanol at 10% (<2 g ethanol/kg body weight/day). At 120 days old, rats were anesthetized and decapitated, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), caspase-3, X-linked inhibitor of apoptosis protein (XIAP), and insulin-like growth factor 1-receptor (IGF-1R); real-time PCR (RT-PCR) to determine caspase-3, XIAP, and IGF-1R gene expression; and transmission electron microscopy (TEM). We identified fragmentation of DNA and an increase in caspase-3 protein and XIAP in Purkinje cells, whereas granule cells exhibited increased caspase-3 and XIAP. IGF-1R expression was unchanged. There was no significant difference in gene expression of caspase-3, XIAP, and IGF-1R. There were an increase in lipid droplets, a reduction in the cellular cytoplasm in electron-dense nuclei, and changes in the myelin sheath in the cerebellar cortex. In conclusion, our data demonstrated that ethanol induced apoptosis in the Purkinje and granule cells of the cerebellum of adult UChA rats.

The estradiol 17-β concentration in mice after treated with ethanolic leaf extract of Azadirachta indica (neem)

NASA Astrophysics Data System (ADS)

Sitasiwi, Agung Janika; Isdadiyanto, Sri; Mardiati, Siti Muflichatun

2017-05-01

This research was conducted to determine the effect of ethanolic leaf extract of Azadirachta indica (Neem) on plasma estradiol 17-β synthesis in mice. Thirty virgin female mice (Swiss Webster strain) between 2.5 and 3 months old (25 ± 2.5 g body weight) were used as the experimental sample. The mice were divided into five groups: K-group were administered tap water; K+ group were administered contraceptive pills; P1 to P3 group were administered orally with ethanolic A. indica leaf extract at doses of 8.4, 11.2, and 14 mg/animal/day, respectively. The regularity of the estrous cycle was monitored during treatment. The mice were sacrificed after being treated orally for 21 days and blood was collected by cardiac puncture under chloroform anesthesia. The estradiol concentration was measured by ELISA. Ovaries were processed with the paraffin method and HE staining. Our results showed that the estrous cycle irregularity of treated groups was higher than K-group. The estradiol concentration was significantly different (p<0.05) compared to the control group (25.02 ± 1.16 pg/mL in the control group and 18.86 ± 2.21 pg/mL in treated group but there was no significant difference (p>0.05) between the treated groups. The atresia follicle number was significantly different (p<0.05), not compared to the control group but between treated groups also. It can be concluded that Neem extracts disrupt the estradiol 17-β concentration by interference with follicle development in the ovaries so that the regularity of estrous cycle was disrupted.

Performance of dairy cows fed high levels of acetic acid or ethanol.

PubMed

Daniel, J L P; Amaral, R C; Sá Neto, A; Cabezas-Garcia, E H; Bispo, A W; Zopollatto, M; Cardoso, T L; Spoto, M H F; Santos, F A P; Nussio, L G

2013-01-01

Ethanol and acetic acid are common end products from silages. The main objective of this study was to determine whether high concentrations of ethanol or acetic acid in total mixed ration would affect performance in dairy cows. Thirty mid-lactation Holstein cows were grouped in 10 blocks and fed one of the following diets for 7 wk: (1) control (33% Bermuda hay + 67% concentrates), (2) ethanol [control diet + 5% ethanol, dry matter (DM) basis], or (3) acetic acid (control diet + 5% acetic acid, DM basis). Ethanol and acetic acid were diluted in water (1:2) and sprayed onto total mixed rations twice daily before feeding. An equal amount of water was mixed with the control ration. To adapt animals to these treatments, cows were fed only half of the treatment dose during the first week of study. Cows fed ethanol yielded more milk (37.9 kg/d) than those fed the control (35.8 kg/d) or acetic acid (35.3 kg/d) diets, mainly due to the higher DM intake (DMI; 23.7, 22.2, and 21.6 kg/d, respectively). The significant diet × week interaction for DMI, mainly during wk 2 and 3 (when acetic acid reached the full dose), was related to the decrease in DMI observed for the acetic acid treatment. There was a diet × week interaction in excretion of milk energy per DMI during wk 2 and 3, due to cows fed acetic acid sustained milk yield despite lower DMI. Energy efficiency was similar across diets. Blood metabolites (glucose, insulin, nonesterified fatty acids, ethanol, and γ-glutamyl transferase activity) and sensory characteristics of milk were not affected by these treatments. Animal performance suggested similar energy value for the diet containing ethanol compared with other diets. Rumen conversion of ethanol to acetate and a concomitant increase in methane production might be a plausible explanation for the deviation of the predicted energy value based on the heat of combustion. Therefore, the loss of volatile compounds during the drying process in the laboratory should be considered when calculating energy content of fermented feedstuffs. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Chronic ethanol intake leads to structural and molecular alterations in the rat endometrium.

PubMed

Martinez, Marcelo; Milton, Flora A; Pinheiro, Patricia Fernanda F; Almeida-Francia, Camila C D; Cagnon-Quitete, Valeria H A; Tirapelli, Luiz F; Padovani, Carlos Roberto; Chuffa, Luiz Gustavo A; Martinez, Francisco Eduardo

2016-05-01

We described the effects of low- and high-dose ethanol intake on the structure and apoptosis signaling of the uterine endometrium of UChA and UChB rats (animals with voluntary ethanol consumption). Thirty adult female rats, 90 days old, were divided into three groups (n = 10/group): UChA rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking < 1.9 g/kg/day; UChB rats fed with 10% (v/v) ethanol ad libitum (free choice for water or ethanol) drinking from 2 to 5 g/kg/day; control rats without ethanol (only water). After 120 days of treatment, rats displaying estrus were euthanized. Uterine epithelial cells of the UCh rats showed dilated cisterns of the rough endoplasmic reticulum, presence of lipid droplets, altered nuclear chromatin, and disrupted mitochondria. The UCh rats exhibited intense atrophied epithelial cells with smaller areas and perimeters of cytoplasm and nuclei. The endometrium of UChA rats showed higher levels of caspase-3 while Xiap and Bcl2 varied from moderate to weak. Both UChA and UChB rats exhibited a stronger immunoreaction to Ki-67 and IGFR-1 on epithelial and stromal cells. Chronic ethanol intake leads to structural and molecular alterations in the uterine endometrium of UCh rats, regardless of low- or high-dose consumption, promoting reproductive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

PubMed

Rose, Jamie H; Karkhanis, Anushree N; Chen, Rong; Gioia, Dominic; Lopez, Marcelo F; Becker, Howard C; McCool, Brian A; Jones, Sara R

2016-05-01

Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined. Five weeks of chronic intermittent ethanol exposure in male C57BL/6 mice were used to examine the role of kappa opioid receptors in chronic ethanol-induced increases in ethanol intake and marble burying, a measure of anxiety/compulsive-like behavior. Drinking and marble burying were evaluated before and after chronic intermittent ethanol exposure, with and without kappa opioid receptor blockade by nor-binaltorphimine (10mg/kg i.p.). Functional alterations in kappa opioid receptors were assessed using fast scan cyclic voltammetry in brain slices containing the nucleus accumbens. Chronic intermittent ethanol-exposed mice showed increased ethanol drinking and marble burying compared with controls, which was attenuated with kappa opioid receptor blockade. Chronic intermittent ethanol-induced increases in behavior were replicated with kappa opioid receptor activation in naïve mice. Fast scan cyclic voltammetry revealed that chronic intermittent ethanol reduced accumbal dopamine release and increased uptake rates, promoting a hypodopaminergic state of this region. Kappa opioid receptor activation with U50,488H concentration-dependently decreased dopamine release in both groups; however, this effect was greater in chronic intermittent ethanol-treated mice, indicating kappa opioid receptor supersensitivity in this group. These data suggest that the chronic intermittent ethanol-induced increase in ethanol intake and anxiety/compulsive-like behaviors may be driven by greater kappa opioid receptor sensitivity and a hypodopaminergic state of the nucleus accumbens. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Effect of chronic ethanol ingestion and exercise training on skeletal muscle in rat.

PubMed

Vila, L; Ferrando, A; Voces, J; Cabral de Oliveira, C; Prieto, J G; Alvarez, A I

2001-09-01

The aim of this study was to investigate the interactive effects of exercise training and chronic ethanol consumption on metabolism, capillarity, and myofibrillar composition in rat limb muscles. Male Wistar rats were treated in separate groups as follows: non exercised-control; ethanol (15%) in animals' drinking water for 12 weeks; exercise training in treadmill and ethanol administration plus exercise for 12 weeks. Ethanol administration decreased capillarity and increased piruvate kinase and lactate dehydrogenase activities in white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase activity and decreased cross-sectional area of type I, IIa, and IIb fibres. Exercise increased capillarity in all four limb muscles and decreased type I fibre area in plantaris. The decreased capillarity effect induced by ethanol in some muscles, was ameliorated when alcohol was combined with exercise. While alcoholic myopathy affects predominantly type IIb fibres, ethanol administration and aerobic exercise in some cases can affect type I and type IIa fibre areas. The exercise can decrease some harmful effects produced by ethanol in the muscle, including the decrease in the fibre area and capillary density.

Effect of Application Propolis as Biocoating on the Physical and Chemical Properties of Tomatoes Stored at Room Temperature

NASA Astrophysics Data System (ADS)

E Putra, R.; Khairannisa, S.; Kinasih, I.

2017-03-01

Tomatoes is considered as one of important horticulture commodities which highly consume by Indonesia consumer. However, this horticulture product is perishable with high rate which reduce quantity and quality of marketable products. One of the method could be used to prevent this problem by application of edible biocoating. In this study, various concentration of ethanolic propolis extract was applied to tomatoes in order to find the effect of propolis coating in tomato preservation and best concentration for application. Tomatoes were grouped into 5 group, namely control group (no coating application), ethanol group (tomato wash with ethanol), and application group (coated with 5%, 10%, and 15% propolis). Variables observed during study were weight change, fruit firmness, total soluble solute, vitamin C, and lycopene. All tomatoes were kept in room temperature for 14 days and observation conducted every 2 days. Result showed that application of 10% propolis as biocoating reduced rate of weight loss and maintained fruit firmness while other variables relatively unaffected by propolis coating.

Aspirin attenuation of alcohol-induced flushing and intoxication in Oriental and Occidental subjects.

PubMed

Truitt, E B; Gaynor, C R; Mehl, D L

1987-01-01

Aspirin (ASA) was tested in a group of 8 Oriental and 3 Occidental subjects who were shown in a previous study to respond to small doses of ethanol (0.06-0.25 g/kg) with facial flushing. They were compared to a similar group of 11 non-flushing Occidental subjects following a larger ethanol dose (0.37 g/kg) to determine if similar effects could be produced in less sensitive individuals. Control tests of blood ethanol and acetaldehyde (AcH) levels (calculated from breath), facial and neck skin temperatures, body sway (Romberg test), blood pressure, heart rate and 10 Subjective High Assessment Scales (SHAS-Judd, 1977) were conducted before and at 15, 30, 60 and 90 minutes after drinking ethanol as vodka in orange juice. The tests were repeated one week later one hour after receiving 0.64 gm of ASA orally. ASA produced slight changes in the early absorption of ethanol and small decreases in AcH levels in the flushing and non-flushing groups. Facial flushing was markedly reduced in the flushing group, but was slightly increased in the non-flushing Occidentals. Body sway was reduced by ASA in both groups. An alcohol-induced increase in heart rate in the flushing group was reduced with no change in blood pressure. SHAS subjective parameters were widely variable, but indicated that ASA produced reduced sleepiness and earlier relaxation in the flushing group. It is concluded that ASA can block alcohol-induced facial flushing in sensitive subjects and also reduces body sway in the Romberg test and alters some subjective feelings of alcohol intoxication.

The effects of a liquid ethanol diet on nutritional status and fluid balance in the rat.

PubMed

Piano, M R; Artwohl, J; Kim, S D; Gass, G

2001-01-01

The liquid ethanol diet is a widely used method of ethanol administration. The purpose of this study was to evaluate fluid balance using a multitude of physiological parameters (electrolytes, osmolality, total serum proteins, fluid intake/output and body weight), during and after the introduction of liquid ethanol diet. Animals were randomized into four different dietary protocols (two control and two ethanol groups) and were placed in metabolic cages for 16 days. Serum electrolytes, as well as the above parameters, were measured before, during and 1 week after the introduction of 9% (v/v) ethanol-containing diet (Lieber-DeCarli: LD). After the first night on 9% (v/v) ethanol LD, animals had significantly decreased diet consumption, urine output and body weight. However, a major finding of this study was that, during the habituation phase, the electrolyte values remained within the normal range for rats and, in particular, serum sodium was not altered at any time point measured in this study. Based upon the findings from this study, it is recommended that body weight be carefully monitored as a measure of the animal's equilibration and physiological adaptation during the initiation of a liquid ethanol diet, since neither the serum sodium nor calculated osmolality values were changed. Our results also highlight the need to offer water to animals during the habituation phase of ethanol consumption. This is because ethanol rats that were offered water ad libitum lost less weight than groups that did not receive water ad libitum, despite consuming the same amount of LD diet.

Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates.

PubMed

Lindquist, Derick H

2013-04-01

Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4-9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure. Copyright © 2013 Elsevier B.V. All rights reserved.

Antihypertensive potential of the aqueous extract which combine leaf of Persea americana Mill. (Lauraceae), stems and leaf of Cymbopogon citratus (D.C) Stapf. (Poaceae), fruits of Citrus medical L. (Rutaceae) as well as honey in ethanol and sucrose experimental model.

PubMed

Dzeufiet, Paul Désiré Djomeni; Mogueo, Amélie; Bilanda, Danielle Claude; Aboubakar, Bibi-Farouck Oumarou; Tédong, Léonard; Dimo, Théophile; Kamtchouing, Pierre

2014-12-17

The present study was designed to evaluate the effects of the aqueous extract obtained from the mixture of fresh leaf of Persea americana, stems and fresh leaf of Cymbopogon citratus, fruits of Citrus medica and honey on ethanol and sucrose induced hypertension in rats. Rats were divided into eight groups of 6 rats each and daily treated for 5 weeks. The control group received distilled water (1 mL/kg) while rats of groups 2, 3 and 4 received ethanol 40 degrees (3 g/kg/day), 10% sucrose as drinking water and the two substances respectively. The remaining groups received in addition to sucrose and ethanol, the aqueous extract (50, 100 and 150 mg/kg) or nifedipine (10 mg/kg) respectively. Many parameters including hemodynamic, biochemical and histopathological were assessed at the end of the study. The concomitant consumption of ethanol and sucrose significantly (p < 0.001) increased the blood pressure and the heart rate compared to distilled water treated-rats. The levels of total cholesterol, LDL-cholesterol, triglycerides, atherogenic index, glucose, proteins, AST, ALT, creatinin, potassium, sodium and albumin increased while the HDL-cholesterol decreased under ethanol and sucrose feeding. Chronic ethanol and sucrose intake significantly decreased the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the contents of reduced glutathione (GSH) and nitrites whereas elevated the malondialdehyde (MDA) levels. Histological analysis revealed among other vascular congestion, inflammation, tubular clarification and thickening of the vessel wall in rats treated with alcohol and sucrose. Administration of the aqueous extract or nifedipine prevented the hemodynamic, biochemical, oxidative and histological impairments induced chronic ethanol and sucrose consumption. Current results suggest that the aqueous extract used in this study possess antihypertensive activity against ethanol and sucrose induced hypertension in rats by the improvement of biochemical and oxidative status, and by protecting liver, kidney and vascular endothelium against damages induced by chronic consumption of ethanol and sucrose.

The Potency of Ethanolic Extract of Sauropus androgynus (L.) Merr Leaves as Therapeutic herbal of Rats (Rattus norvegicus) Peptic Ulcer Model Induced by Aspirin

NASA Astrophysics Data System (ADS)

Roosdiana, A.; Yudandi, S. A.; Erika, A.

2018-01-01

Peptic ulcer is an erosion of the mucosa gaster and duodenum. Aspirin can increase the activity of ROS in duodenum leading to be oxidative stress condition, followed by the increase expression of TNF-α and changes in the duodenum histopathology. Ethanolic extract from Sauropus androgynus (L.) Merr leaves contains flavonoid compound that act as antioxidants. The research aimed to study the therapeutic effect of Sauropus androgynus (L.) Merr leaves towards the expression of TNF-α and the duodenum histopathology. The study used five groups: the negative control group, the positive control group (peptic ulcer), and three therapeutic groups. Peptic ulcer induced by aspirin 200 mg/kg BW given orally once a day for five days. The therapeutic group (dose 16.2 mg/200 g BW, 32.4 mg/200 g BW, 48.6 mg/200 g BW) administrated orally once a day for fourteen days. Expression of TNF-α were analyzed by ANOVA followed by Tukey test (α=5%) and histopathology description of duodenum were analyzed descriptive qualitative. The result showed that treatment of the ethanolic extract from Sauropus androgynus (L.) Merr leaves at dose 48.6 mg/200 g BW was the effective dosage. The conclusion of this research indicate that ethanolic extract from Sauropus androgynus (L.) Merr leaves can be used as alternative therapy peptic ulcer towards decrease the expression of TNF-α and repair duodenum histopathology such as structure of epithelial duodenum, vile and decrease of inflammatory cell and vascular vasodilatation

Prenatal alcohol exposure and cellular differentiation: a role for Polycomb and Trithorax group proteins in FAS phenotypes?

PubMed

Veazey, Kylee J; Muller, Daria; Golding, Michael C

2013-01-01

Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell-cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell's identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes--the Polycomb and Trithorax proteins--are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder.

Comparative effect of palm vitamin E and ranitidine on the healing of ethanol-induced gastric lesions in rats

PubMed Central

Jaarin, Kamsiah; Renuvathani, M; Nafeeza, M I; Gapor, M T

1999-01-01

The effect of palm vitamin E on the healing of ethanol-induced gastric lesion was compared with ranitidine. Fifty-six male rats of Sprague-Dawley species (200–250 g of weight) were randomly divided into three groups (N = 14). Gastric mucosal injury was induced by orogastric tube administration of 0.5 ml 100% ethanol. Immediately after induction, Group I (k) rats was fed with a normal diet (control), group II (p) was fed palm vitamin E enriched diet (150 mg/kg food), Group III(r) was treated with ranitidine 30 mg/kg body weight intraperitoneally and Group IV (p + r) was fed with palm vitamin E and treated with ranitidine 30 mg/kg body weight intraperitoneally of the same dose. The rats were killed at the end of 1 week and 3 weeks of treatment or feeding. The rate of gastric healing was faster in palm vitamin E treated group compared to control and ranitidine treated groups as shown by a lower mean ulcer index. The effect was seen as early as the first week of treatment whereas ranitidine did not show any healing effect even after 3 weeks of therapy. Neither gastric acidity nor gastric mucus production are involved in gastroprotective effect of palm vitamin E. The most probable mechanism is via reducing lipid peroxidation process as shown by a significant decrease in gastric MDA PMID:10607016

Effect of Ethanolic Leaf Extract of Senna Fistula on some Haematological Parameters, Lipid Profile and Oxidative Stress in Alloxan-induced Diabetic Rats.

PubMed

Ayinla, Tayo Maryam; Owoyele, Victor B; Yakubu, Toyin M

2015-12-20

Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. The disease is also known to adversely affect some haematological parameters and cause dyslipidemia. This study was designed to investigate the effect of chronic administration of ethanolic leave extract of Senna fistula on haematological values, oxidative stress and dyslipidemia in experimental diabetic rats. Twenty-four albino rats weighing 120-150 g were divided into 4 experimental groups of six rats each; control, diabetic untreated, diabetic treated with glibenclamide and diabetic treated with 100 mg/kg b.w of Senna fistula. Diabetes was induced by 100 mg/kg b.w. of alloxan monohydrates. The control and diabetic groups received normal saline while the diabetic treated groups were administered with 5mg/kg and 100mg/kg body weight of glibenclamide and ethanolic leaves extract of Senna fistula respectively for 28 days. At the end of experimental period blood samples were taken from the animals for the determination of Red blood cells (RBC), packed cell volume (PCV), Haemoglobin concentration (Hb), total cholesterol, triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and malondialdehyde (MDA), marker of lipid peroxidation. The result showed that in diabetic rats, PCV, RBC and Hb were decreased but the application of the extract increased the parameters. Similarly, the result showed a significant increase in total cholesterol, TG and LDL level of the diabetic group when compared with the control, glibenclamide and extract treated diabetic groups, however, there was no significant difference in HDL level in all the groups. The result also showed a significant decrease in elevated MDA of diabetic treated rats. These findings suggest that ethanolic leaves extract of Senna fistula might improve the diabetic induced disturbances of some haematological parameters, reduces the plasma lipid imbalances and decreases the production of free radicals associated with diabetes.

Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats

PubMed Central

Shnitko, Tatiana A.; Spear, Linda P.; Robinson, Donita L.

2015-01-01

Rationale Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. Objectives We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Methods Rats received intermittent intragastric ethanol, water or nothing during adolescence. In adulthood, electrically-evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Results Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50% in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. Conclusions The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats, and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age. PMID:26487039

Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats.

PubMed

Sailani, M R; Moeini, H

2007-07-01

The present study was undertaken to evaluate the effects of alcohol extracts of Ruta graveolens and Cannabis sativa that were used traditionally in medieval Persian medicine as male contraceptive drugs, on spermatogenesis in the adult male rats. Ethanol extracts of these plants were obtained by the maceration method. The male rats were injected intraperitionaly with C. sativa and R. graveolens 5% ethanol extracts at dose of 20 mg/day for 20 consecutive days, respectively. Twenty-four hours after the last treatment, testicular function was assessed by epididymal sperm count. The statistical results showed that the ethanol extracts of these plants reduced the number of sperms significantly (P=0.00) in the treatment groups in comparison to the control group. The results also showed that the group, treated by extract of R. graveolens reduced spermatogenesis more than the group treated by extracts of C. sativa. The present study demonstrated the spermatogenesis reducing properties of the ethanol extracts of R. graveolens and C. sativa in the adult male wistar rats but more studies are necessary to reveal the mechanism of action that is involved in spermatogenesis.

Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats

PubMed Central

Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E.; Spear, Norman E.

2014-01-01

Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17–20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. PMID:24355072

Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats.

PubMed

Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E; Spear, Norman E

2014-02-01

Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17-20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development. Published by Elsevier Inc.

Effect of sildenafil citrate (Viagra) and ethanol on the Albino rat testis: a scanning electron microscopic approach.

PubMed

Sivasankaran, T G; Udayakumar, R; Elanchezhiyan, C; Sabhanayakam, Selvi

2008-02-01

The effects of sildenafil citrate with ethanol on the rat testis was studied using scanning electron microscopy. Male Albino rats were divided into 8 groups, each being treated for a maximum of 45 days as follows. In the 4 short-term treatment groups, control rats were administered normal saline orally, whereas experimental animals were fed sildenafil citrate (Viagra) 1 microg/g with 18% ethanol (5 g/kg body weight), which was given orally as a single dose. After 1, 2.5, 4 and 24h the rats were killed. In the 4 long-term treatment groups, daily continuous doses of drug and ethanol with a single dosage were given for 15, 30 and 45 days and the animals killed 4h after the last dosage. Changes in the testis were compared with the normal healthy rat testis. The use of a scanning electron microscope for evaluation of the changes in the testis is more suitable for observation of the surface and morphological shapes of the tissue structures.

Antimicrobial photodynamic therapy with photosensitizer in ethanol improves oxidative status and gingival collagen in a short-term in periodontitis.

PubMed

Pillusky, Fernanda Maia; Barcelos, Raquel Cristine Silva; Vey, Luciana Taschetto; Barin, Luisa Machado; de Mello Palma, Victor; Maciel, Roberto Marinho; Kantorski, Karla Zanini; Bürger, Marilise Escobar; Danesi, Cristiane Cademartori

2017-09-01

This study evaluated the antimicrobial photodynamic therapy (aPDT) effects using the methylene blue (MB) in ethanol 20% on systemic oxidative status and collagen content from gingiva of rats with periodontitis. Rats were divided into five experimental groups: NC (negative control; no periodontitis); PC (positive control; periodontitis without any treatment); SRP (periodontitis and scaling and root planing), aPDT I (periodontitis and SRP+aPDT+MB solubilized in water), and aPDT II (periodontitis and SRP+aPDT+MB solubilized in ethanol 20%). After 7days of removal of the ligature, the periodontal treatments were performed. At 7/15/30days, gingival tissue was removed for morphometric analysis. The erythrocytes were used to evaluate systemic oxidative status. PC group showed higher lipoperoxidation levels at 7/15/30days. aPDT indicated a protective influence in erythrocytes at 15days observed by the elevation in levels of systemic antioxidant defense. aPDT II group was the only one that restored the total collagen area in 15days, and recovered the type I collagen area at the same time point. aPDT as an adjunct to the SRP can induce the systemic protective response against oxidative stress periodontitis-induced and recover the gingival collagen, thus promoting the healing periodontal, particularly when the MB is dissolved in ethanol 20%. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary supplementation with Cynodon dactylon (L.) enhances innate immunity and disease resistance of Indian major carp, Catla catla (Ham.).

PubMed

Kaleeswaran, B; Ilavenil, S; Ravikumar, S

2011-12-01

Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P < 0.05) enhanced most of the non-specific immune parameters tested. Among the experimental diet groups, significantly increased response of non-specific immunity was seen in group III (5%). Disease resistant analysis against Aeromonas hydrophila was performed in control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative percent survival rate (RPS) was observed in treated samples, which is directly proportional to concentration of the extract. Additionally, electron microscopic studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the experimental diet groups than the control. All these experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish. Copyright © 2011 Elsevier Ltd. All rights reserved.

Antidiabetic, antihyperlipidemic, and antioxidant activities of Musa balbisiana Colla. in Type 1 diabetic rats

PubMed Central

Borah, Mukundam; Das, Swarnamoni

2017-01-01

Objectives: To evaluate the antidiabetic, antihyperlipidemic, and antioxidant activities of the ethanolic extracts of the flowers and inflorescence stalk of Musa balbisiana Colla. in streptozotocin (STZ)-induced Type 1 diabetic rats. Materials and Methods: Diabetes was induced in male Wistar albino rats (150–200 g) by single intraperitoneal injection of STZ (60 mg/kg b.w. i.p.). Albino rats (n = 25) were divided into five groups, of which five animals each. Group A (normal control) and Group B (diabetic control) received normal saline (10 ml/kg/day p.o.), whereas Group C and Group D received 250 mg/kg/day p.o. of flower and inflorescence stalk ethanolic extracts, respectively, for 2 weeks. Group E (diabetic standard) received 6 U/kg/day s.c of Neutral Protamine Hagedorn insulin. Fasting blood sugar, serum insulin, catalase (CAT), malondialdehyde (MDA), and serum lipid profile were estimated at specific intervals of time. Effect of the extracts on intestinal glucose absorption was also evaluated to know the probable mechanism of action. Results: Diabetic control exhibited significant increase in blood glucose, serum cholesterol, triglycerides, low-density lipoprotein, serum MDA levels and decreased serum CAT, and high-density lipoprotein levels which were significantly reverted by flower and inflorescence stalk ethanolic extracts after 2 weeks. Serum insulin levels were in increased (P < 0.05), and intestinal glucose absorption decreased significantly (P < 0.01) in extract-treated groups. Conclusion: Flower and inflorescence stalk of M. balbisiana Colla. possess significant antidiabetic, antihyperlipidemic, and antioxidant activities in STZ-induced Type 1 diabetic rats. PMID:28458426

Ultrasound-guided interventional therapy for recurrent ovarian chocolate cysts.

PubMed

Wang, Lu-Lu; Dong, Xiao-Qiu; Shao, Xiao-Hui; Wang, Si-Ming

2011-10-01

The aim of this study was to determine the effectiveness of ultrasound-guided interventional therapy in the treatment of postoperative recurrent chocolate cysts. The 198 patients enrolled in this study were divided into three groups. In group 1, the saline washing group, the cavity of the cyst was washed thoroughly with warm saline. In group 2, the ethanol short-time retention group, after washing with saline, the cyst was injected with 95% ethanol with a volume of half of the fluid aspirated from the cyst. Ten minutes later, the rest of the ethanol was aspirated. In group 3, the ethanol retention group, the procedures were the same as with the ethanol short-time retention group, except that 95% of the ethanol was retained in the cyst. An ultrasound examination was performed in the third, sixth and 12th months after therapy. The chocolate cyst cure rate was significantly higher in the ethanol retention group (96%, 66/69) than in the ethanol short-time retention group (82%, 56/68) and no case was cured in the first group (saline washing). We conclude that ultrasound-guided injection and 95% ethanol retention are an effective therapy for the treatment of postoperative recurrent chocolate cysts. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Diuretic Activity of Ethanolic Root Extract of Mimosa Pudica in Albino Rats

PubMed Central

SL, Shruthi; PS, Vaibhavi; VH, Pushpa; AM, Satish; Sibgatullah, Mohammad

2015-01-01

Introducation Diuretics are the drugs which increase the urine output. This property is useful in various pathological conditions of fluid overload. The presently available diuretics have lot of adverse effects. Our study has evaluated the diuretic activity of ethanolic root extract of Mimosa pudica as an alternative/new drug which may induce diuresis. Aim To evaluate the diuretic activity of ethanolic root extract of Mimosa pudicaa in albino rats. Materials and Methods Ethanolic root extract of Mimosa pudica (EEMP) was prepared using soxhlet’s apparatus. Albino rats were divided into 5 groups of 6 rats each. Group-I (Control) received distilled water 25ml/kg orally. Group-II (Standard) received Furosemide 20mg/kg orally. Group-III received EEMP 100 mg/kg, Group-IV received EEMP 200 mg/kg and Group-V received EEMP 400 mg/kg. The urine samples were collected for all the groups upto 5 hours after dosing and urine volume was measured. Urine was analysed for electrolytes (Na+, K+ and Cl-). ANOVA, Dunnet’s test and p-values were measured and data was analysed. Results EEMP exhibited significant diuretic activity by increasing urine volume and also by enhancing elimination of Sodium (Na+), Potassium (K+) and Chloride (Cl-) at doses of 100 and 200mg/kg. Conclusion EEMP possesses significant diuretic activity and has a beneficial role in volume overload conditions. PMID:26870704

Effect of chlorhexidine and ethanol on push-out bond strength of fiber posts under cyclic loading.

PubMed

Cecchin, Doglas; Giacomin, Mateus; Farina, Ana Paula; Bhering, Cláudia Lopes; Mesquita, Marcelo Ferraz; Ferraz, Caio Cezar

2014-02-01

To investigate the effects of pretreatment with 2% chlorhexidine in a gel base (CHX) and 100% ethanol (EtOH) on the bond strength between fiber posts relined with resin composite and root dentin under cyclic loading. Forty bovine incisor roots were divided into four groups after phosphoric acid etching: group 1 (control), irrigation with physiological saline solution; group 2, 5 min pretreatment with CHX; group 3, 1 min pretreatment with EtOH; group 4, 5 min pretreatment with CHX followed by 1 min with EtOH. Fiber posts relined with resin composite were cemented with RelyX ARC and the etch-and-rinse adhesive system Scotchbond Multi-Purpose. Each group was randomly divided into two subgroups: 24 h of storage (immediate groups) and cyclic loading (loading groups) with 250,000 cycles in a controlled chewing simulator. All roots were sectioned transversely and push-out tests were performed. Failure modes were observed and the bond strength means were analyzed using ANOVA and Tukey's test (a = 0.05). The mean values for the bond strength test (MPa) in immediate groups were: group 1, 5.44 ± 1.48; group 2, 5.57 ± 1.41; group 3, 5.49 ± 1.48; group 4, 5.57 ± 1.42. Immediate groups showed similar bond strength values (p > 0.05). In the cyclic loading groups, the bond strength values were: group 1, 2.80 ± 0.79; group 2, 4.02 (1.30); group 3, 4.50 ± 1.67; group 4, 4.97 ± 2.00. After cyclic loading, a significant decrease in the control group was observed (p < 0.05), while CHX pretreatment resulted in intermediate values (p < 0.05) and EtOH alone or associated with CHX preserved the bond strength values (p > 0.05). Chlorhexidine and/or ethanol pretreatment preserved the bond strength of the fiber post after cyclic loading.

Bifunctionalized organic-inorganic charged nanocomposite membrane for pervaporation dehydration of ethanol.

PubMed

Tripathi, Bijay P; Kumar, Mahendra; Saxena, Arunima; Shahi, Vinod K

2010-06-01

Chitosan was modified into N-p-carboxy benzyl chitosan (NCBC) by introducing an aromatic ring grafted with acidic -COOH group and highly stable and cross-linked nanostructured NCBC-silica composite membranes were prepared for pervaporation dehydration of water-ethanol mixture. These membranes were tailored to comprise three regions namely: hydrophobic region, highly charged region and selective region, in which weak acidic group (-COOH) was grafted at organic segment while strong acidic group (-SO(3)H) was grafted at inorganic segment to achieve high stability and less swelling in water-ethanol mixture. Cross-linking density and NCBC-silica content in membrane matrix has been systematically optimized to control the nanostructure of the developed polymer matrix for studying the effects of molecular structure on the swelling, and PV performance. Among prepared membranes, nanocomposite membrane with 3h cross-linking time and 90% (w/w) of NCBC-silica content (PCS-3-3) exhibited 1.66×10(-4)cm(3)(STP) cm/cm(2) s cmHg water permeability (P(W)), while 1.35×10(-7) cm(3)(STP) cm/cm(2) s cmHg ethanol permeability (P(EtOH)) of developed membrane and 1231 PV selectivity factor at 30 °C for separating water from 90% (w/w) ethanol mixture. Copyright © 2010 Elsevier Inc. All rights reserved.

Effects of ampicillin, cefazolin and cefoperazone treatments on GLT-1 expressions in the mesocorticolimbic system and ethanol intake in alcohol-preferring rats.

PubMed

Rao, P S S; Goodwani, S; Bell, R L; Wei, Y; Boddu, S H S; Sari, Y

2015-06-04

Chronic ethanol consumption is known to downregulate expression of the major glutamate transporter 1 (GLT-1), which increases extracellular glutamate concentrations in subregions of the mesocorticolimbic reward pathway. While β-lactam antibiotics were initially identified as potent upregulators of GLT-1 expression, only ceftriaxone has been extensively studied in various drug addiction models. Therefore, in this study, adult male alcohol-preferring (P) rats exposed chronically to ethanol were treated with other β-lactam antibiotics, ampicillin, cefazolin or cefoperazone (100mg/kg) once daily for five consecutive days to assess their effects on ethanol consumption. The results demonstrated that each compound significantly reduced ethanol intake compared to the saline-treated control group. Importantly, each compound significantly upregulated both GLT-1 and pAKT expressions in the nucleus accumbens and prefrontal cortex compared to saline-treated control group. In addition, only cefoperazone significantly inhibited hepatic aldehyde dehydrogenase-2 enzyme activity. Moreover, these β-lactams exerted only a transient effect on sucrose drinking, suggesting specificity for chronically inhibiting ethanol reward in adult male P rats. Cerebrospinal fluid concentrations of ampicillin, cefazolin or cefoperazone have been confirmed using high-performance liquid chromatography. These findings demonstrate that multiple β-lactam antibiotics demonstrate efficacy in reducing alcohol consumption and appear to be potential therapeutic compounds for treating alcohol abuse and/or dependence. In addition, these results suggest that pAKT may be an important player in this effect, possibly through increased transcription of GLT-1. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Prenatal ethanol exposure decreases hippocampal /sup 3/H-vinylidene kainic acid binding in 45-day-old rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farr, K.L.; Montano, C.Y.; Paxton, L.L.

1988-11-01

The effect of prenatal ethanol exposure on the kainate-sensitive subtype of glutamate receptor binding sites was studied using in vitro /sup 3/H-vinylidene kainic acid (VKA) autoradiography. Pregnant Sprague-Dawley rats were fed a liquid diet containing either 3.35% or 6.7% ethanol throughout gestation. Pair-fed dams received isocalorically matched liquid diets and a lab chow ad lib group served as control for paired feeding. At 45 days of age, the offspring were sacrificed and their brains analyzed for specific /sup 3/H-VKA binding. Compared to pair-fed controls, specific /sup 3/H-VKA binding was reduced by 13% to 32% in dorsal and ventral hippocampal CA3more » stratum lucidum, entorhinal cortex and cerebellum of 45-day-old rats whose mothers consumed either 3.35% or 6.7% ethanol diets. The binding site reductions were statistically significant only in the ventral hippocampal formation and entorhinal cortex of the 3.35% ethanol diet group rats. Saturation of binding studies in the ventral hippocampal formation of 3.35% ethanol rats indicated that the decrease in specific /sup 3/H-VKA binding was due to a decrease in the total number of binding sites. Given the excitatory effect of kainic acid on the spontaneous firing rate of hippocampal CA3 pyramidal neurons, the reduction of kainate-sensitive glutamate binding in this region is consistent with the electrophysiological observation of decreased spontaneous activity of CA3 pyramidal neurons in fetal alcohol rats.« less

Forced ethanol ingestion by Wistar rats from a juvenile age increased voluntary alcohol consumption in adulthood, with the involvement of orexin-A.

PubMed

Mendoza-Ruiz, Luis-Gabriel; Vázquez-León, Priscila; Martínez-Mota, Lucía; Juan, Eduardo Ramírez San; Miranda-Páez, Abraham

2018-08-01

Human adolescents who drink alcohol are more likely to become alcoholics in adulthood. Alcohol administration (intraperitoneally) or drinking (in a 2-bottle free choice paradigm) during the juvenile/adolescent age of rats promotes voluntary alcohol consumption in adulthood. On the other hand, there is growing evidence that the orexinergic system plays a role in several rewarded behaviors, including alcohol ingestion. Since it is unknown what effect is exerted in adulthood by forced oral ethanol intake and/or administration of orexin-A (OX-A) in juvenile rats, the present study aimed to evaluate this question. A group of male Wistar rats was forced to drink ethanol (10% v/v) as the only liquid in the diet from weaning (postnatal day 21) to postnatal day 67 (46 days), followed by a forced withdrawal period. An age-matched group was raised drinking tap water (control). OX-A or its vehicle was microinjected intracerebroventricularly (i.c.v.) (1 nmol/0.6 μL) to explore its effect as well. Locomotor activity and voluntary ethanol consumption were later assessed in all groups. The rats forced to consume ethanol early in life showed an elevated level of ambulation and alcohol ingestion in adulthood. A single injection of OX-A increased locomotor activity and acute ethanol intake in rats with or without prior exposure to alcohol at the juvenile stage. In conclusion, forced ethanol consumption in juvenile rats led to increased voluntary alcohol drinking behavior during adulthood, an effect likely facilitated by OX-A. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

Synthesis of Toll-like receptor 4 in Kupffer cells and its role in alcohol-induced liver disease.

PubMed

Zuo, Guoqing; Gong, Jianping; Liu, Chang'an; Wu, Chuanxin; Li, Shengwei; Dai, Lili

2003-02-01

To observe the synthesis of Toll-like receptor (TLR) 4 protein and its mRNA expression in Kupffer cells (KCs) and evaluate the role of TLR 4 in liver injury to rats through alcohol-induced liver disease. Twenty-eight Wistar rats were divided into two groups: ethanol-fed (group E) and control (group C). Group E rats were given ethanol at a dose of 5 - 12 g x kg(-1) x d(-1), while group C received dextrose. Animals from both groups were killed at 4 and 8 weeks. The KCs were isolated and synthesis of TLR 4 protein was determined by laser scanning confocal microscopy. TLR 4 mRNA expression in KCs was determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. The levels of endotoxin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in plasma were determined. Changes in liver pathology were observed. Laser scanning confocal microscopy showed that the intensity of fluorescence of TLR 4 protein in group E was stronger than group C. Ethanol administration led to a significant increase in TLR 4 mRNA expression in group E compared with group C (P < 0.05). The concentrations of plasma endotoxin, TNF-alpha and IL-6 were higher in group E than in group C (P < 0.05). Liver sections from rats in group E demonstrated marked pathological changes. Ethanol administration can lead to the synthesis of TLR 4 protein and its gene expression in KCs, indicating that TLR 4 may play a major role in the development of alcohol-induced liver injury.

CENTRAL REINFORCING EFFECTS OF ETHANOL ARE BLOCKED BY CATALASE INHIBITION

PubMed Central

Nizhnikov, Michael Edward; Molina, Juan Carlos; Spear, Norman

2007-01-01

Recent studies have systematically indicated that newborn rats are highly sensitive to ethanol’s positive reinforcing effects. Central administrations of ethanol (25–200 mg %) associated with an olfactory conditioned stimulus (CS) promote subsequent conditioned approach to the CS as evaluated through the newborn’s response to a surrogate nipple scented with the CS. It has been shown that ethanol’s first metabolite, acetaldehyde, exerts significant reinforcing effects in the central nervous system. A significant amount of acetaldehyde is derived from ethanol metabolism via the catalase system. In newborn rats catalase levels are particularly high in several brain structures. The present study tested the effect of catalase inhibition on central ethanol reinforcement. In the first experiment, pups experienced lemon odor either paired or unpaired with intracisternal (i.c.) administrations of 100 mg% ethanol. Half of the animals corresponding to each learning condition were pretreated with i.c. administrations of either physiological saline or a catalase inhibitor (sodium-azide). Catalase inhibition completely suppressed ethanol reinforcement in paired groups without affecting responsiveness to the CS during conditioning or responding by unpaired control groups. A second experiment tested whether these effects were specific to ethanol reinforcement or due instead to general impairment in learning and expression capabilities. Central administration of an endogenous kappa opioid receptor agonist (dynorphin A-13) was employed as an alternative source of reinforcement. Inhibition of the catalase system had no effect on the reinforcing properties of dynorphin. The present results support the hypothesis that ethanol metabolism regulated by the catalase system plays a critical role in determination of ethanol reinforcement in newborn rats. PMID:17980789

Ethanol and tobacco smoke increase hepatic steatosis and hypoxia in the hypercholesterolemic apoE-/- mouse: implications for a “multi-hit” hypothesis of fatty liver disease

PubMed Central

Bailey, Shannon M.; Mantena, Sudheer K.; Millender-Swain, Telisha; Cakir, Yavuz; Jhala, Nirag C.; Chhieng, David; Pinkerton, Kent E.; Ballinger, Scott W.

2009-01-01

While epidemiologic studies indicate that combined exposures to cigarette smoke and alcohol increase risk and severity of liver diseases, the molecular mechanisms responsible for hepatotoxicity are unknown. Similarly, emerging evidence indicates a linkage among hepatic steatosis and cardiovascular disease. Herein, we hypothesize that combined exposure to alcohol and environmental tobacco smoke (ETS) on a hypercholesterolemic background increase liver injury through oxidative/nitrative stress, hypoxia, and mitochondrial damage. To test this, male apoE-/- mice were exposed to an ethanol-containing diet, ETS alone, or a combination, and histology and functional endpoints were compared to filtered air, ethanol-naïve controls. While ethanol consumption induced a mild steatosis, combined exposure to ethanol + ETS resulted in increased hepatic steatosis, inflammation, alpha smooth muscle actin, and collagen. Exposure to ethanol + ETS induced the largest increase on CYP2E1 and iNOS protein, as well as increased 3-nitrotyrosine, mtDNA damage, and decreased cytochrome c oxidase protein compared to all other groups. Similarly, the largest increase in HIF1α expression was observed in the ethanol + ETS group indicating enhanced hypoxia. These studies demonstrate that ETS increases alcohol-dependent steatosis and hypoxic stress. Therefore, ETS may be a key environmental “hit” that accelerates and exacerbates alcoholic liver disease in hypercholesterolemic apoE-/- mice. PMID:19280709

Gastroprotective and mucosa homeostatic activities of coconut milk and water on experimentally induced gastropathies in male wistar rats.

PubMed

Ajeigbe, K O; Owonikoko, W M; Egbe, V; Iquere, I; Adeleye, G

2017-10-01

In this biphasic study, 45 male wistar rats were divided into 9 groups. In Phase 1, Group 1 was treated with normal saline and served as the overall control, group 2 was treated with 95% Ethanol and represents the ulcer control, groups 3 and 4 received coconut water (CW; 4ml/100g BWt) and milk (CM; 4ml/100g BWt) for 4weeks while group 5 received Omeprazole (Omep; 20mg/kg BWt) during terminal week. 95% Ethanol-induced ulceration followed the treatments in all except group 1. In the second phase, Group 1 was the overall control, group 2 served as ulcer control by receiving acetic acid only, group 3 received coconut milk, and group 4 received omep. CM and omep were administered post-ulcer induction for 3 and 6days twice daily. Blood collection after 1hour was through cardiac puncture for haemocytometry, and gastric tissues harvested for histopathological investigations. Results showed significantly reduced ulcer score and gastric lesion index in Omep, CW and CM groups compared to ulcer control. WBC, neutrophil, lymphocyte counts in Omep, CW and CM groups were significantly reduced compared to ulcer and overall control groups. C-reactive protein was significantly reduced in CM compared to control. Neutrophil Infiltration score reduced while mucus cell density increased significantly in Omep; CM compared to control. EGFR and CD 31 assessment revealed significantly higher expressions in coconut-milk group compared to the ulcer control. We conclude that the protective effects of coconut (water and milk) is expressed by inflammation suppression, upregulation of mucus cell population and catalyses mucosa homeostasis via angiogenesis and mucosal cell proliferation following mucosa. erosion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alcohol exposure during development: analysis of effects on female sexual behavior.

PubMed

Gass, Justin T; Jenkins, William J; Marino, Melissa D; Lugo, Joaquin N; Kelly, Sandra J

2007-12-01

Alcohol exposure during development has been shown to alter a variety of social behaviors in both humans and rodents. Sexual behavior in rodents has been well characterized and lends itself to a detailed investigation of the manner in which ethanol impacts this particular social behavior. Rats were exposed to ethanol during both the prenatal and early postnatal period (ET). Control groups included rats exposed to the administration procedures alone (intubated-control) and nontreated controls (NC). Sexual behavior of intact naïve female rats in estrus was assessed in adulthood (approximately postnatal day 90) and activity was measured by the number of crossings between chambers in the 3-chamber test apparatus. A separate study examined the olfactory preferences for 4 odors by intact naïve female rats in all 3 groups. The 4 odors were the odors resulting from 1 hour of occupation of the test chamber by an intact male, 1 hour of occupation of the test chamber by a gonadectomized male, 0.5 ml of urine from an intact male, and 0.5 ml of urine from a gonadectomized male. ET female rats showed a reduced return latency after ejaculation compared to both control groups. There was a trend toward a reduction in percent exits after all forms of male behavior in the ET animals compared to the control groups. No significant differences across groups were seen in the lordosis quotient, activity, or the behavior of the nonexperimental male. ET female rats showed a reduced preference for the odor from the intact male compared to both control groups and a reduced preference for the odor from the gonadectomized male compared to NC females only. These data suggest that ethanol exposure during the prenatal and postnatal period in females alters sexual motivation and changes the processing of olfactory cues and possibly coital cues from male rats.

Chronic ethanol ingestion, type 2 diabetes mellitus, and brain-derived neurotrophic factor (BDNF) in rats.

PubMed

Jung, Kyu-In; Ju, Anes; Lee, Hee-Mi; Lee, Seong-Su; Song, Chan-Hee; Won, Wang-Youn; Jeong, Jae-Seung; Hong, Oak-Kee; Kim, Jae-Hwa; Kim, Dai-Jin

2011-01-07

Chronic alcohol consumption contributes to the development of type 2 diabetes mellitus (T2DM) while decreasing the level of brain-derived neurotrophic factor (BDNF). BDNF may be an important regulator of glucose metabolism, so it may be associated with an increased risk for T2DM in alcoholism. We evaluated the association of chronic heavy alcohol exposure, T2DM and BDNF level. Ten week-old type 2 diabetic OLETF rats and non-diabetic LETO rats of similar weight were used. The rats were randomized by weight into four treatment groups: (1) OLETF-Ethanol (O-E, n=13), (2) OLETF-Control (O-C, n=15), (3) LETO-Ethanol (L-E, n=11), and (4) LETO-Control (L-C, n=14). The ethanol groups were fed an isocaloric liquid diet containing ethanol while the control groups were fed with the same diet containing maltose-dextran over a 6-week period using a pair-feeding control model in order to regulate different caloric ingestion. After 6 weeks of feeding, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and BDNF levels were analyzed. Prior to IP-GTT, the mean glucose levels in the O-E, O-C, L-E, and L-C groups were 90.38±12.84, 102.13±5.04, 95.18±6.43, and 102.36±4.43mg/dL, respectively. Thirty minutes after intraperitoneal injection, the mean glucose levels were 262.62±63.77, 229.07±51.30, 163.45±26.63, and 156.64±34.42mg/dL, respectively; the increased amount of the mean glucose level in the O-E group was significantly higher than that in the O-C group (p<0.05). One hundred twenty minutes after intraperitoneal injection, the mean glucose levels were 167.38±45.37, 121.20±18.54, 106.73±6.94, and 104.57±9.49mg/dL, respectively; the increased amount of the mean glucose level in the O-E group was significantly higher than that in the O-C group (p<0.01). The difference in mean glucose levels between the O-E group and O-C group was still significant even after adjusting for time (p<0.05). Mean BDNF levels were 405.95±326.16, 618.23±462.15, 749.18±599.93, and 1172.00±839.17pg/mL, respectively; mean BDNF level in the O-E group was significantly lower than the L-C group (p<0.05). In conclusion, the results of the present study suggest that chronic heavy alcohol ingestion may aggravate T2DM and may possibly lower BDNF level. Copyright © 2010. Published by Elsevier Ireland Ltd.

Antihyperglycaemic effects of ethanol extracts of Carica papaya and Pandanus amaryfollius leaf in streptozotocin-induced diabetic mice.

PubMed

Sasidharan, Sreenivasan; Sumathi, Vello; Jegathambigai, Naidu Rameshwar; Latha, Lachimanan Yoga

2011-12-01

Diabetes mellitus is a global disease that is increasing in an alarming rate. The present study was undertaken to study the antidiabetic effect of the ethanol extracts of Carica papaya and Pandanus amaryfollius on streptozotocin-induced diabetic mice. The results of the present study indicated that there was no significant difference in the body weight of the treated groups when compared to diabetic control. Whereas, there was significant (P < 0.05) decrease in the blood glucose level of the plant-treated groups compared to the diabetic control. Histologically the pancreas of the treated groups indicated significant regeneration of the β-cells when compared to the diabetic control. The liver tissues of the treated group indicated a reduction in fatty changes and pyknotic nucleus. The kidney tissues of the treated groups indicated significant recovery in the cuboidal tissue. The results from the phytochemical screening indicated the presence of flavonoids, alkaloids, saponin and tannin in C. papaya and P. amaryfollius. The antidiabetic effect of C. papaya and P. amaryfollius observed in the present study may be due to the presence of these phytochemicals.

Neuroimmunophilin GPI-1046 reduces ethanol consumption in part through activation of GLT1 in alcohol-preferring rats.

PubMed

Sari, Y; Sreemantula, S N

2012-12-27

We have previously shown that ceftriaxone, β-lactam antibiotic known to upregulate glutamate transporter 1 (GLT1), reduced ethanol intake in alcohol-preferring (P) rats. GLT1 is a glial glutamate transporter that regulates the majority of extracellular glutamate uptake. We tested in this study the effects of neuroimmunophilin GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate), known also to upregulate GLT1 expression, in ethanol intake in P rats. Male P rats had concurrent access to free choice of 15% and 30% ethanol, water, and food for five weeks. On Week 6, P rats continued in this drinking and food regimen and they were administered either 10 or 20mg/kg GPI-1046 (i.p.), or a vehicle for five consecutive days. Body weight, ethanol intake, and water consumption were measured daily for 8 days starting on Day 1 of GPI-1046 or vehicle i.p. injections. We have also tested the effect of GPI-1046 (20mg/kg) on daily sucrose (10%) intake. The data revealed significant dose-dependent effects in the reduction of ethanol intake starting 48 h after the first treatment with GPI-1046 throughout treatment and post-treatment periods. There were also dose-dependent increases in water intake. However, GPI-1046 treatment did not affect the body weight of all animals nor sucrose intake. Importantly, GPI-1046 (20mg/kg) increased GLT1 level compared to all groups in nucleus accumbens core (NAc-core). Alternatively, GPI-1046 (10mg/kg) upregulated GLT1 level in NAc-core compared to vehicle (ethanol naïve) group. Moreover, both doses of GPI-1046 increased significantly GLT1 level in the prefrontal cortex (PFC) compared to ethanol naïve vehicle group. GPI-1046 (20mg/kg) increased GLT1 level in PFC compared to naïve control group that was exposed to water and food only. These findings demonstrated that neuroimmunophilin GPI-1046 attenuates ethanol intake in part through the upregulation of GLT1 in PFC and NAc-core. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Preliminary study on fractions' activities of red betel vine (Piper crocatum Ruiz & Pav) leaves ethanol extract toward Mycobacterium tuberculosis

NASA Astrophysics Data System (ADS)

Rachmawaty, Farida Juliantina; Julianto, Tatang Shabur; Tamhid, Hady Anshory

2018-04-01

This research aims to identify the antimycobacterial activity of fraction of red betel vine leaves ethanol extract (methanol fraction, ethyl acetate, and chloroform) toward M. tuberculosis. Red betel vine leaves ethanol extract was made with maceration method using ethanol solvent 70%. Resulted extract was then fractionated using Liquid Vacuum Chromatography (LVC) with methanol, ethyl acetate, and chloroform solvent. Each fractionation was exposed to M. tuberculosis with serial dilution method. Controls of fraction, media, bacteria, and isoniazid as standard drug were included in this research. The group of compound from the most active fraction was then identified. The research found that the best fraction for antimycobacterial activity toward M. tuberculosisis chloroform fraction. The compound group of chloroform fraction was then identified. The fraction contains flavonoid, tannin, alkaloid, and terpenoid. The fraction of methanol, ethyl acetate, and chloroform from red betel vine leaves has antimycobacterial activity toward M. tuberculosis. Chloroform fraction has the best antimycobacterial activity and it contains flavonoid, tannin, alkaloid, and terpenoid.

Aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) protect against sodium arsenite-induced hepatotoxicity in Wistar rats.

PubMed

Gbadegesin, M A; Odunola, O A

2010-11-25

We evaluated the effects of aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) on sodium arsenite-induced hepatotoxicity in Wistar rats. We observed that treatment of the animals with the extracts before or just after sodium arsenite administration significantly (p < 0.05) reduced mean liver and serum γ-Glutamyl transferase (γGT), and serum alkaline phosphatase (ALP) activities when compared with the group administered the toxin alone. In addition, treatments of the animals with aqueous or ethanolic extract of O. basilicum before the administration of sodium arsenite resulted in the attenuation of the sodium arsenite-induced aspartate and alanine aminotransferase activities: ALT (from 282.6% to 167.7% and 157.8%), AST (from 325.1% to 173.5% and 164.2%) for the group administered sodium arsenite alone, the aqueous extracts plus sodium arsenite, and ethanolic extracts plus sodium arsenite respectively, expressed as percentage of the negative control. These findings support the presence of hepatoprotective activity in the O.basilicum extracts.

Brain glucose content in fetuses of ethanol-fed rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pullen, G.; Singh, S.P.; Snyder, A.K.

1986-03-01

The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4more » and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.« less

Chinese yellow wine and red wine inhibit matrix metalloproteinase-2 and improve atherosclerotic plaque in LDL receptor knockout mice.

PubMed

Guo, Hangyuan; Liu, Longbin; Shi, Yafei; Sun, Aijing; Xu, Fukang; Chi, Jufang; Huang, Dilai

2010-06-01

Our previous study found that Chinese yellow wine could inhibit the production of homocysteine (HCY) induced extracellular matrix metalloproteinase-2 (MMP-2) in the cultured rat vascular smooth muscle cells. Little is known about the relationship between Chinese yellow wine and atherosclerosis or MMP-2 in vivo. Thirty-two LDL Receptor knockout mice on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. They were randomly divided into yellow wine group (n = 8), red wine group (n = 8), ethanol group (n = 8), and control group (n = 8), they were sacrificed after 14 weeks. There were no significant differences with plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in the four groups. Plasma HCY was significantly decreased in the yellow wine group compared to the other three groups (P < 0.01). Yellow wine and red wine groups significantly reduced the atherosclerosis lesion area compared to ethanol and control groups (P < 0.001). However, there was no significant discrepancy between the yellow wine group and red wine group. Compared to the control group and ethanol group, the production of MMP-2 reduced 26.8% and 23.6% in the aortic sinus and the activation of MMP-2 reduced 32.6% and 27.3% in the aortic arch in the yellow wine group; the production of MMP-2 reduced 25.7% and 22.4% in the aortic sinus and the activation of MMP-2 reduced 30.2% and 26.6% in the aortic arch in the red wine group. These results suggest that Chinese yellow wine and red wine can inhibit MMP-2 and improve atherosclerosis, and maybe both Chinese yellow wine and red wine have beneficial effects on cardiovascular disease by inhibiting MMP-2.

Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

PubMed

Yang, Wenjuan; Gao, Jinhang; Tai, Yang; Chen, Meng; Huang, Luming; Wen, Shilei; Huang, Zhiyin; Liu, Rui; Li, Jing; Tang, Chengwei

2016-07-01

To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.

PubMed

Gainza-Cirauqui, M L; Nieminen, M T; Novak Frazer, L; Aguirre-Urizar, J M; Moragues, M D; Rautemaa, R

2013-03-01

Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus (OLP), oral lichenoid lesion (OLL) and oral leukoplakia (OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL (n = 6), OLP (n = 16), OL (n = 6) and controls (n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism. © 2012 John Wiley & Sons A/S. All rights reserved.

The effects of binge-pattern alcohol consumption on orthodontic tooth movement

PubMed Central

de Araujo, Cristiano Miranda; Johann, Aline Cristina Batista Rodrigues; Camargo, Elisa Souza; Tanaka, Orlando Motohiro

2014-01-01

OBJECTIVE: This study aimed to assess tissue changes during orthodontic movement after binge-pattern ethanol 20% exposure. METHODS: Male Wistar rats (n = 54) were divided into two groups. The control group (CG) received 0.9% saline solution, while the experimental group (EG) received 20% ethanol in 0.9% saline solution (3 g/kg/day). On the 30th day, a force of 25 cN was applied with a nickel-titanium closed coil spring to move the maxillary right first molar mesially. The groups were further divided into three subgroups (2, 14 and 28 days). Tartrate-resistant acid phosphatase and picrosirius were used to assess bone resorption and neoformation, respectively. Data were compared by two-way ANOVA, Tukey's HSD, Games-Howell and chi-square test. Significance level was set at 5%. RESULTS: There was a decrease in the number of osteoclasts in EG at day 28. The percentage of collagen showed no interaction between group and time. CONCLUSION: Binge-pattern 20% ethanol promoted less bone resorption at the end of tooth movement, thereby suggesting delay in tooth movement. PMID:25628085

Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

PubMed Central

Dreumont, Sarah E.; Cunningham, Christopher L.

2013-01-01

Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury.

PubMed

Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

2016-10-14

To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.

Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury

PubMed Central

Osna, Natalia A; Feng, Dan; Ganesan, Murali; Maillacheruvu, Priya F; Orlicky, David J; French, Samuel W; Tuma, Dean J; Kharbanda, Kusum K

2016-01-01

AIM To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. METHODS Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. CONCLUSION To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage. PMID:27784962

Antiperoxidative and antiinflammatory effect of Sida cordifolia Linn. on quinolinic acid induced neurotoxicity.

PubMed

Swathy, S S; Panicker, Seema; Nithya, R S; Anuja, M M; Rejitha, S; Indira, M

2010-09-01

Sida cordifolia is a plant belonging to the Malvaceae family used in many ayurvedic preparations. This study aimed at assessing the effects of ethanolic extract of Sida cordifolia root on quinolinic acid (QUIN) induced neurotoxicity and to compare its effect with the standard drug deprenyl in rat brain. Rats were divided into six groups: (1) control group (2) QUIN (55 microg/100 g bwt/day) (3) 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (4) Deprenyl (100 microg/100 g bwt/day) (5) QUIN (55 microg/100 g bwt/day) + 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (6) QUIN (55 microg/100 g bwt/day) + Deprenyl (100 microg/100 g bwt/day). At the end of the experimental period a status of lipid peroxidation products, protein peroxidation product, activities of the scavenging enzymes and the activities of the inflammatory markers were analyzed. Results revealed that the lipid peroxidation products decreased and the activities of the scavenging enzymes increased significantly in the brain of the plant extract treated group, deprenyl treated group and also in the coadminstered groups. The activities of markers of inflammatory responses such as cyclooxygenase and lipoxygenase were found to be significantly increased in the QUIN treated rats and this was decreased upon the administration of plant extract and deprenyl. In short, the study revealed that 50% ethanolic extract of Sida cordifolia has got potent antioxidant and antiinflammatory activity and the activity is comparable with the standard drug deprenyl.

Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right-side heart implantation.

PubMed

Lü, Wei-Dong; Wang, An-Ping; Wu, Zhong-Shi; Zhang, Ming; Hu, Tie-Hui; Lei, Guang-Yan; Hu, Ye-Rong

2012-10-01

This study aimed to investigate the effect of decellularization plus photooxidative crosslinking and ethanol pretreatment on bioprosthetic tissue calcification. Photooxidatively crosslinked acellular (PCA) bovine jugular vein conduits (BJVCs) and their photooxidized controls (n = 5 each) were sterilized in a graded concentration of ethanol solutions for 4 h, and used to reconstruct dog right ventricular outflow tracts. At 1-year implantation, echocardiography showed similar hemodynamic performance, but obvious calcification for the photooxidized BJVC walls. Further histological examination showed intense calcium deposition colocalized with slightly degraded elastic fibers in the photooxidized BJVC walls, with sparsely distributed punctate calcification in the valves and other areas of walls. But PCA BJVCs had apparent degradation of elastic fibers in the walls, with only sparsely distributed punctate calcification in the walls and valves. Content assay demonstrated comparable calcium content for the two groups at preimplantation, whereas less calcium for the PCA group in the walls and similar calcium in the valvular leaflets compared with the photooxidized group at 1-year retrieval. Elastin content assay presented the conduit walls of PCA group had less elastin content at preimplantation, but similar content at 1-year retrieval compared with the photooxidized group. Phospholipid analysis showed phospholipid extraction by ethanol for the PCA group was more efficacious than the photooxidized group. These results indicate that PCA BJVCs resist calcification in right-side heart implantation owing to decellularization, further photooxidative crosslinking, and subsequent phospholipid extraction by ethanol at preimplantation. Copyright © 2012 Wiley Periodicals, Inc.

Development of an ethanol model using social insects: IV. Influence of ethanol on the aggression of Africanized honey bees (Apis mellifera L.).

PubMed

Abramson, Charles I; Place, Aaron J; Aquino, Italo S; Fernandez, Andrea

2004-06-01

Experiments were designed to determine whether ethanol influenced aggression in honey bees. Two experiments are reported. In Exp. 1, harnessed honey bees were fed a 1%, 5%, 10%, or 20% ethanol solution. Two control groups received either a sucrose solution only or no pretreatment, respectively. The dependent variable was the number of sting extensions over 10 min. Analysis showed that aggression in harnessed bees was not influenced by prior ethanol consumption. Because there was some suspicion that the extension of the sting apparatus may be hindered by harnessing, and the authors wanted to use a design that increased ecological validity, Exp. 2 was conducted with free-flying bees. Sucrose or 20% ethanol solutions were placed in front of beehives, and the number of stings on a leather patch dangled in front of the hive served as the dependent variable. The experiment was terminated after 5 hr. because bees exposed to ethanol became dangerously aggressive. A unique aspect of the study was that Africanized honey bees were used.

Effects of maternal chronic alcohol administration in the rat: lactation performance and pup's growth.

PubMed

Murillo-Fuentes, L; Artillo, R; Carreras, O; Murillo, L

2001-08-01

A fostering/crossfostering analysis of the effects of maternal ethanol exposure on lactation performance and offspring growth was performed. Wistar rats were kept under one of the three experimental nutritional treatments: alcohol-treated (EG), pair-fed-treated (PFG) (as a nutritional control of alcohol-associated malnutrition), and control or normal diet (CG). Rats from the EG group were accustomed to increased amounts of ethanol (5% during the first week to 20% in the fourth week). The 20% ethanol level was maintained throughout three additional weeks and during gestational and lactational period. Daily food intake, fluid consumption, body weight and gestational parameters were studied in control (CG), pair-fed (PFG) and ethanol dams (EG). At birth, half the litters were fostered to other dams of the same treatment (GLG) and half were cross-fostered to dams of the opposite treatment (GG, LG). No cross-fostering analyses were performed on the pair-fed group. Offspring body weight was controlled throughout lactation. Liver, kidney and spleen weights as well as milk consumption were also studied at the end of lactation period. In dams, a significant reduction of body weight was described throughout the suckling period. No ethanol detrimental effects were observed on body weight at birth, but in spite of a normal birth weight, alcohol during lactation was responsible for a growth deficit. Milk consumption was significantly reduced in offspring exposed to ethanol during gestation and/or lactation. Curiously, prenatal alcohol exposure affects adversely the suckling behaviour in pups at the time of weaning. In our study, alcohol treatment and malnutrition affects liver and spleen weights. However, malnutrition decreases spleen weights more than alcohol treatment. In the case of the kidney weights the alcohol decreases kidney weight more than malnutrition. Collectively, the data from the present study show similar effects following pre/postnatal and postnatal alcohol exposure. The findings suggest that chronic alcohol administration during gestation and/or lactation adversely affects pup growth at weaning as indicated by its effect on milk consumption, pup and organ weight.

Repeated light-dark phase shifts modulate voluntary ethanol intake in male and female high alcohol-drinking (HAD1) rats.

PubMed

Clark, James W; Fixaris, Michael C; Belanger, Gabriel V; Rosenwasser, Alan M

2007-10-01

Chronic disruption of sleep and other circadian biological rhythms, such as occurs in shift work or in frequent transmeridian travel, appears to represent a significant source of allostatic load, leading to the emergence of stress-related physical and psychological illness. Recent animal experiments have shown that these negative health effects may be effectively modeled by exposure to repeated phase shifts of the daily light-dark (LD) cycle. As chronobiological disturbances are thought to promote relapse in abstinent alcoholics, and may also be associated with increased risk of subsequent alcohol abuse in nonalcoholic populations, the present experiment was designed to examine the effects of repeated LD phase shifts on voluntary ethanol intake in rats. A selectively bred, high alcohol-drinking (HAD1) rat line was utilized to increase the likelihood of excessive alcoholic-like drinking. Male and female rats of the selectively bred HAD1 rat line were maintained individually under a LD 12:12 cycle with both ethanol (10% v/v) and water available continuously. Animals in the experimental group were subjected to repeated 6-hour LD phase advances at 3 to 4 week intervals, while control rats were maintained under a stable LD cycle throughout the study. Contact-sensing drinkometers were used to monitor circadian lick patterns, and ethanol and water intakes were recorded weekly. Control males showed progressively increasing ethanol intake and ethanol preference over the course of the study, but males exposed to chronic LD phase shifts exhibited gradual decreases in ethanol drinking. In contrast, control females displayed decreasing ethanol intake and ethanol preference over the course of the experiment, while females exposed to experimental LD phase shifts exhibited a slight increase in ethanol drinking. Chronic circadian desynchrony induced by repeated LD phase shifts resulted in sex-specific modulation of voluntary ethanol intake, reducing ethanol intake in males while slightly increasing intake in females. While partially contrary to initial predictions, these results are consistent with extensive prior research showing that chronic stress may either increase or decrease ethanol intake, depending on strain, sex, stressor type, and experimental history. Thus, repeated LD phase shifts may provide a novel chronobiological model for the analysis of stress effects on alcohol intake.

Ameliorative effect of Opuntia ficus indica juice on ethanol-induced oxidative stress in rat erythrocytes.

PubMed

Alimi, Hichem; Hfaeidh, Najla; Bouoni, Zouhour; Sakly, Mohsen; Rhouma, Khémais Ben

2013-05-01

The aim of the present study was to investigate the efficacy of Opuntia ficus indica f. inermis fruit juice (OFIj) on reversing oxidative damages induced by chronic ethanol intake in rat erythrocytes. OFIj was firstly analyzed with HPLC for phenolic and flavonoids content. Secondly, 40 adult male Wistar rats were equally divided into five groups and treated for 90 days as follows: control (C), ethanol-only 3 g/kg body weight (b.w) (E), low dose of OFIj 2 ml/100 g b.w+ethanol (Ldj+E), high dose of OFIj 4 ml/100 g b.w+ethanol (Hdj+E), and only a high dose of OFIj 4 ml/100g b.w (Hdj). HPLC analysis indicated high concentrations of phenolic acids and flavonoids in OFIj. Ethanol treatment markedly decreased the activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and the level of reduced glutathione (GSH). Changes in the erythrocyte's antioxidant ability were accompanied by enhanced oxidative modification of lipids (increase of malondialdeyde level) and proteins (increase in carbonyl groups). Interestingly, pre-administration of either 2 ml/100 g b.w or 4 ml/100 g b.w of OFIj to ethanol-intoxicated rats significantly reversed decreases in enzymatic as well as non enzymatic antioxidants parameters in erythrocytes. Also, the administration of OFIj significantly protected lipids and proteins against ethanol-induced oxidative modifications in rat erythrocytes. The beneficial effect of OFIj can result from the inhibition of ethanol-induced free radicals chain reactions in rat erythrocytes or from the enhancement of the endogenous antioxidants activities. Copyright © 2011 Elsevier GmbH. All rights reserved.

Effect of ethanolic Neem (Azadirachta indica) leaf extract as an herb contraceptive on Hepato-somatic Index of the male mice (Mus musculus)

NASA Astrophysics Data System (ADS)

Janika Sitasiwi, Agung; Isdadiyanto, Sri; Muflichatun Mardiati, Siti

2018-05-01

Neem has been known as herb contraceptive plant which shows an antifertility effect both in male and female rats. The anti-fertility compound of Neem has the same potencies to interfere with or affect the function of several organs. The Hepato-somatic index (HSI) reflects the value of toxic compounds that enter the animal body also. HSI values can also be used to assess animal health levels. A study to examine the effect of ethanolic extract of Neem as an herb contraceptive to the hepato-somatic index of male mice has been done. Neem leaf was collected from the campus area, dried, mashed then extracted with ethanol 70%. Mature male Swiss Webster mice with 25-30 grams in weight were used as laboratory animals. Mice were divided into 4 groups: P0 (given distilled water), P1, P2, and P3 were given Neem leaf extract with 8.4, 11.2 and 14 mg/KgBW/day respectively. Each treatment group had six replications. Treatment was given orally for 21 days. The body weight was measured every week until the end of treatment. The mice were anesthetized with chloroform at the end of treatment, continued by dissecting and isolating liver isolation. The isolated liver is then weighed to determine the HSI value. Data were analyzed with ANOVA followed by DMRT test. The results showed that the body weight of control group showed a significant difference (p<0.05) to the treatment group. The hepatic weights and HSI values of the control group showed nonsignificant differences (p>0.05) with the P1 and P2 treatment groups but showed a significant difference (p<0.05) with the P3 treatment group. It can be concluded that the exposure of ethanolic Neem leaves extract as herb contraceptive affects liver function which causes the increase of hepatic weight and HSI value.

Pairings of ethanol sipper with food induces Pavlovian autoshaping of ethanol drinking in rats: evidence of long-term retention and effects of sipper duration.

PubMed

Tomie, Arthur; Sparta, Dennis R; Silberman, Yuval; Interlandi, Jeneen; Mynko, Alise; Patterson-Buckendahl, Patricia; Pohorecky, Larissa A

2002-01-01

This study asks if repeated Pavlovian pairings of a sipper tube (conditioned stimulus, CS) with food (unconditioned stimulus, US) will induce Pavlovian autoshaping conditioned responses (CRs), consisting of drinking of either 6% ethanol or water from the sipper CS. This study also tests predictions derived from the autoshaping model by asking if sipper CS-directed drinking will be retained, despite the absence of training for several weeks, and, in addition, if drinking rate is a negative function of sipper CS duration. Autoshaping procedures, conducted in two daily sessions, consisted of the brief insertion of the sipper tube CS followed by the response-independent presentation of food US. For the Ethanol group (n = 8), the sipper CS contained 6% ethanol, whereas for the Water group (n = 8), the sipper CS contained tap water. Saccharin fading procedures were employed, whereas for both groups, during days 1-19, the sipper CS contained 0.1% saccharin, and thereafter across training days the concentration of saccharin was gradually reduced (0.07, 0.035, 0.0%). Following elimination of saccharin, both groups were maintained in their home cages during a 27-day retention interval, and then re-evaluated for autoshaping of drinking of unsweetened ethanol and water. Thereafter, across days, the duration of access to the sipper CS (5.0, 7.5, 10.0, 15.0 s) during each autoshaping trial was increased. Both groups increased drinking across the first 19 days of training with sipper CS-food US pairings, and, at 0.0% saccharin, the Ethanol group consumed 14.76 ml of 6% ethanol per day, resulting in a daily ethanol consumption of 2.77 g/kg. For both groups, daily levels of drinking before and after the 27-day retention interval were comparable, attesting to the durability of the acquired drinking effects. At each CS duration, the Ethanol group consumed more millilitres of fluid per day than did the Water group, and for the Ethanol group, peak drinking of 24.0 ml of 6% ethanol per day was observed at the 10 s CS duration. For both groups, drinking rate (millilitres of fluid consumed per second of CS duration), was a declining monotonic function of CS duration, resulting in a daily ethanol consumption of approximately 4.2 g/kg for the Ethanol group. These data reveal that these sipper CS-food US autoshaping procedures induce drinking in rats that is durable and negatively related to increasing CS duration. The effects of both variables are consistent with the hypothesis that drinking from the sipper CS is a Pavlovian autoshaping CR. Autoshaping of drinking in the Water group is observed despite the absence of water deprivation, and even more fluid is consumed by the Ethanol group than by the Water group. The high volumes of ethanol consumed during brief daily sessions suggest that Pavlovian autoshaping procedures may provide an animal learning model of binge drinking.

A small group of neurosecretory cells expressing the transcriptional regulator apontic and the neuropeptide corazonin mediate ethanol sedation in Drosophila.

PubMed

McClure, Kimberly D; Heberlein, Ulrike

2013-02-27

In the fruit fly Drosophila melanogaster, as in mammals, acute exposure to a high dose of ethanol leads to stereotypical behavioral changes beginning with increased activity, followed by incoordination, loss of postural control, and eventually, sedation. The mechanism(s) by which ethanol impacts the CNS leading to ethanol-induced sedation and the genes required for normal sedation sensitivity remain largely unknown. Here we identify the gene apontic (apt), an Myb/SANT-containing transcription factor that is required in the nervous system for normal sensitivity to ethanol sedation. Using genetic and behavioral analyses, we show that apt mediates sensitivity to ethanol sedation by acting in a small set of neurons that express Corazonin (Crz), a neuropeptide likely involved in the physiological response to stress. The activity of Crz neurons regulates the behavioral response to ethanol, as silencing and activating these neurons affects sedation sensitivity in opposite ways. Furthermore, this effect is mediated by Crz, as flies with reduced crz expression show reduced sensitivity to ethanol sedation. Finally, we find that both apt and crz are rapidly upregulated by acute ethanol exposure. Thus, we have identified two genes and a small set of peptidergic neurons that regulate sensitivity to ethanol-induced sedation. We propose that Apt regulates the activity of Crz neurons and/or release of the neuropeptide during ethanol exposure.

A Small Group of Neurosecretory Cells Expressing the Transcriptional Regulator apontic and the Neuropeptide corazonin Mediate Ethanol Sedation in Drosophila

PubMed Central

2013-01-01

In the fruit fly Drosophila melanogaster, as in mammals, acute exposure to a high dose of ethanol leads to stereotypical behavioral changes beginning with increased activity, followed by incoordination, loss of postural control, and eventually, sedation. The mechanism(s) by which ethanol impacts the CNS leading to ethanol-induced sedation and the genes required for normal sedation sensitivity remain largely unknown. Here we identify the gene apontic (apt), an Myb/SANT-containing transcription factor that is required in the nervous system for normal sensitivity to ethanol sedation. Using genetic and behavioral analyses, we show that apt mediates sensitivity to ethanol sedation by acting in a small set of neurons that express Corazonin (Crz), a neuropeptide likely involved in the physiological response to stress. The activity of Crz neurons regulates the behavioral response to ethanol, as silencing and activating these neurons affects sedation sensitivity in opposite ways. Furthermore, this effect is mediated by Crz, as flies with reduced crz expression show reduced sensitivity to ethanol sedation. Finally, we find that both apt and crz are rapidly upregulated by acute ethanol exposure. Thus, we have identified two genes and a small set of peptidergic neurons that regulate sensitivity to ethanol-induced sedation. We propose that Apt regulates the activity of Crz neurons and/or release of the neuropeptide during ethanol exposure. PMID:23447613

Increased intracellular localization of brain GLUT-1 transporter in response to ethanol during chick embryogenesis.

PubMed

Carver, F M; Shibley, I A; Miles, D S; Pennington, J S; Pennington, S N

1999-10-01

Fetal exposure to ethanol is associated with growth retardation of the developing central nervous system. We have previously described a chick model to study the molecular mechanism of ethanol effects on glucose metabolism in ovo. Total membrane fractions were prepared from day 4, day 5, and day 7 chick embryos exposed in ovo to ethanol or to vehicle. By Western blotting analysis, ethanol exposure caused a mean 7- to 10-fold increase in total GLUT-1 and a 2-fold increase in total GLUT-3. However, glucose uptake by ethanol-treated cells increased by only 10%. Analysis of isolated plasma (PM) and intracellular (IM) membranes from day 5 cranial tissue revealed a mean 25% decrease in GLUT-1 in the PM and a 66% increase in the IM in the ethanol group vs. control. The amount of PM GLUT-3 was unchanged but that of IM GLUT-3 was significantly decreased. The data suggest that GLUT-3 cell surface expression may be resistant to the suppressive effects of ethanol in the developing brain of ethanol-treated embryos. The overall increase in GLUT-1 may reflect a deregulation of the transporter induced by ethanol exposure. The increased IM localization and decreased amount of PM GLUT-1 may be a mechanism used by the ethanol-treated cell to maintain normal glucose uptake despite the overall increased level of the transporter.

Protective effects of Rutin against methanol induced acute toxic optic neuropathy: an experimental study.

PubMed

Taşlı, Nurdan Gamze; Çimen, Ferda Keskin; Karakurt, Yücel; Uçak, Turgay; Mammadov, Renad; Süleyman, Bahadır; Kurt, Nezahat; Süleyman, Halis

2018-01-01

To determine the effects of Rutin on methanol induced optic neuropathy and compare the results with the effects of ethanol. Totally 30 rats were divided into 5 groups, with 6 rats in each group as follows: healthy controls (C), methotrexate (MTX), methotrexate+methanol (MTM), methotrexate+methanol+ethanol (MTME) and methotrexate+ methanol+Rutin (MTMR). In all rabbits except those of the control group, MTX, diluted in sterile serum physiologic, 0.3 mg/kg per oral was applied for 7d by the aid of a tube. After this procedure to the rats of MTM, MTME and MTMR groups, 20% methanol with a dose of 3 g/kg per oral was given by the aid of a tube. In MTME group, 4h after the application of methanol, 20% ethanol was applied by the same way with a dose of 0.5 g/kg. On the other hand, in MTMR group 4h after the application of methanol, Rutin, which was dissolved in distilled water, was applied by the same way with a dose of 50 mg/kg. There were statistically significant differences in tissue 8-hydroxy-2 deoxyguanine (8-OHdG), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO). glutathione peroxidase (tGSH) and superoxide dismutase (SOD) levels between groups ( P <0.001). In MTMR group tissue 8-OHdG, IL-1β, MDA, and MPO levels were similar with the healthy controls but significantly different than the other groups. In histopathological evaluations, in MTX group there was moderate focal destruction, hemorrhage and decrease in number of astrocytes and oligodendrocytes; in MTM group there was severe destruction and edema with decrease in number of astrocytes and oligodendrocytes; in MTME group there was mild hemorrhage, mild edema, mildly dilated blood vessels with congestion while in MTMR group, optic nerve tissue was resembling the healthy controls. Rutin may prevent methanol-induced optic neuropathy via anti-inflammatory effects and decreasing the oxidative stress. New treatment options are warranted in this disease to avoid loss of vision in patients.

Morphologic variations in the pineal gland of the albino rat after a chronic alcoholisation process.

PubMed

Martínez-Salvador, J; Ruiz-Torner, A; Blasco-Serra, A; Martínez-Soriano, F; Valverde-Navarro, A A

2018-04-01

We studied the effect of alcohol on the pineal gland of 48 male Wistar rats. Animals were divided into control and experimental groups. The experimental group underwent a previous progressive alcoholisation period with ethanol diluted in water at a concentration of 40%. Animals were sacrificed at 3, 6, 9 and 12 months, and the ultrastructure, karyometric indices, and number of synaptic bodies in the pineal gland were analysed. The results showed progressive morphologic alterations in the ethanol-treated animals, which culminated in fatty degeneration of the pineal parenchyma after 6 months. The karyometric indices decreased in both the central and peripheral areas compared with the control group. Moreover, the seasonal rhythmicity observed in the controls disappeared in the experimental groups, whose number of different populations of synaptic bodies (synaptic ribbons and synaptic spherules) considerably lowered with inversion of their normal seasonal rhythm. These results support that chronic alcoholisation leads to fatty degeneration of the pineal parenchyma, and a considerable alteration in nuclear functional rhythms and synaptic bodies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats

PubMed Central

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

Objective: To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Materials and Methods: Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. Results: At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Conclusions: Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women. PMID:25097281

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure

PubMed Central

Balaraman, Sridevi; Idrus, Nirelia M.; Miranda, Rajesh C.; Thomas, Jennifer D.

2017-01-01

Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol’s developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol’s long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4–9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4–21. On PD 22, subjects were sacrificed, and RNA isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was normalized with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p<0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p<0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by ethanol. These findings have important implications for the mechanisms by which choline may serve as a potential treatment for FASD. PMID:28433422

Comparison of acetic acid and ethanol sclerotherapy for simple renal cysts: clinical experience with 86 patients.

PubMed

Cho, Young Jun; Shin, Ji Hoon

2016-01-01

To compare the efficacy and treatment session numbers of acetic acid to that of ethanol sclerotherapy for the treatment of simple renal cysts. Between February 2004 and June 2013, 86 patients with simple renal cysts underwent percutaneous aspiration and injection of 50 %-acetic-acid (42 cysts) and 95 %-ethanol (44 cysts). The patient demographics, volume reduction rate, number of treatment sessions, and complications were then analyzed. The volume reduction rate was 94.1 ± 7.6 % in the 50 %-acetic acid group and 94.7 ± 11.7 % in the 95 %-ethanol group, and without a statistical difference. The rates of complete remission, partial remission, and no response were 57.1, 42.9 and 0 %, respectively, for the acetic acid group, and 70.5, 25.0, and 4.5 %, respectively, for the ethanol group. No statistical difference was observed between the two groups. Compared to the acetic acid group, the ethanol group had a higher number of treatment sessions, i.e. 1.10 ± 0.30 in the acetic acid group and 1.80 ± 0.79 in the ethanol group. Mild flank pain was a minor complication that occurred in both groups. Acetic acid seems to have equivalent sclerosing effects on simple renal cysts compared with those of ethanol despites of fewer treatment sessions.

Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats.

PubMed

Kim, Soo-Jeong; Ju, Anes; Lim, Seul-Gi; Kim, Dai-Jin

2013-11-13

Alcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. OLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated. Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group. These results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels. © 2013. Published by Elsevier Inc. All rights reserved.

SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho

Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kgmore » and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of repeated intermittent ethanol intoxication in the frontal cortex.« less

Effect of fruit extract on renal stone formation and kidney injury in rats.

PubMed

Partovi, Nasrin; Ebadzadeh, Mohammad Reza; Fatemi, S Jamilaldin; Khaksari, Mohammad

2018-05-01

This study investigated the effect of oral administration of Cactus fruit extracts on calcium oxalate deposition, malondialdehyde (MDA) and superoxide dismutase (SOD) activity in rat model. About 42 rats were used for the study. The animals were divided into seven groups. Control group maintained on regular rat food and drinking water throughout the study period, whereas in other groups nephrolithiasis was induced by ethylene glycol. Rats in kidney stone group were sacrificed after 28 days and all remaining groups after 58 days. Treatment groups were treated with 1 and 100 mg/kg of aqueous and ethanolic extracts of Cactus fruit for 30 days. After treatment, SOD activity was increased and MDA was decreased significantly. CaOx depositions were decreased significantly, especially in ethanolic extract of Cactus fruit in high dose (100 mg/kg).

Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits.

PubMed

Dub, Abdallah M; Dugani, Aisha M

2013-01-01

The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, which has known cardiovascular health benefits, including those on blood pressure, cholesterol level, and thrombogenesis. All previous animal and clinical studies investigating the beneficial antithrombotic effects of olives have focused on olive oil and a few on olive leaves (OLEs). In this study, the ethanolic extract of OLE was evaluated for its antithrombotic activity in the rabbit model of thrombosis induced by ligature of the vena cava and intravenous administration of tissue thromboplastin. Pre-treatment with 100 or 200 mg/kg per day of the ethanolic extract for 8 weeks significantly prolonged the prothrombin time (PT) in comparison to the control group (12.10±0.35 sec and 14.38±0.29 sec vs. 10.8±0.32 sec, p<0.05 and 0.001, respectively). In comparison to the control group, the same doses had no statistically significant effect on thrombus weight (16.85±0.67 mg, 16.32±0.35 mg, and 17.81±0.75 mg; p=0.18 and 0.06) or on activated partial thromboplastin time (APTT) (19.17±0.33 sec, 19.12±0.73 sec, and 18.97±0.41 sec; p=0.36 and 0.43, respectively). One important finding in this study concerns thrombus morphology. In the extract treatment groups, the thrombus was filament-like and did not adhere to blood vessel walls, whereas in the control group the thrombus was thick and almost completely occluded the vein. Therefore, these results suggest that OLE ethanolic extract can modify the extrinsic coagulation pathway as evidenced by the prolongation of PT and changes in thrombus morphology, enough to justify further research to evaluate its possible antithrombotic effects.

Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits.

PubMed

Dub, Abdallah M; Dugani, Aisha M

2013-05-22

The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, which has known cardiovascular health benefits, including those on blood pressure, cholesterol level, and thrombogenesis. All previous animal and clinical studies investigating the beneficial antithrombotic effects of olives have focused on olive oil and a few on olive leaves (OLEs). In this study, the ethanolic extract of OLE was evaluated for its antithrombotic activity in the rabbit model of thrombosis induced by ligature of the vena cava and intravenous administration of tissue thromboplastin. Pre-treatment with 100 or 200 mg/kg per day of the ethanolic extract for 8 weeks significantly prolonged the prothrombin time (PT) in comparison to the control group (12.10 ± 0.35 sec and 14.38 ± 0.29 sec vs. 10.8 ± 0.32 sec, p < 0.05 and 0.001, respectively). In comparison to the control group, the same doses had no statistically significant effect on thrombus weight (16.85 ± 0.67 mg, 16.32 ± 0.35 mg, and 17.81 ± 0.75 mg; p = 0.18 and 0.06) or on activated partial thromboplastin time (APTT) (19.17 ± 0.33 sec, 19.12 ± 0.73 sec, and 18.97 ± 0.41 sec; p = 0.36 and 0.43, respectively). One important finding in this study concerns thrombus morphology. In the extract treatment groups, the thrombus was filament-like and did not adhere to blood vessel walls, whereas in the control group the thrombus was thick and almost completely occluded the vein. Therefore, these results suggest that OLE ethanolic extract can modify the extrinsic coagulation pathway as evidenced by the prolongation of PT and changes in thrombus morphology, enough to justify further research to evaluate its possible antithrombotic effects.

Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits

PubMed Central

Dub, Abdallah M.; Dugani, Aisha M.

2013-01-01

The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, which has known cardiovascular health benefits, including those on blood pressure, cholesterol level, and thrombogenesis. All previous animal and clinical studies investigating the beneficial antithrombotic effects of olives have focused on olive oil and a few on olive leaves (OLEs). In this study, the ethanolic extract of OLE was evaluated for its antithrombotic activity in the rabbit model of thrombosis induced by ligature of the vena cava and intravenous administration of tissue thromboplastin. Pre-treatment with 100 or 200 mg/kg per day of the ethanolic extract for 8 weeks significantly prolonged the prothrombin time (PT) in comparison to the control group (12.10±0.35 sec and 14.38±0.29 sec vs. 10.8±0.32 sec, p<0.05 and 0.001, respectively). In comparison to the control group, the same doses had no statistically significant effect on thrombus weight (16.85±0.67 mg, 16.32±0.35 mg, and 17.81±0.75 mg; p=0.18 and 0.06) or on activated partial thromboplastin time (APTT) (19.17±0.33 sec, 19.12±0.73 sec, and 18.97±0.41 sec; p=0.36 and 0.43, respectively). One important finding in this study concerns thrombus morphology. In the extract treatment groups, the thrombus was filament-like and did not adhere to blood vessel walls, whereas in the control group the thrombus was thick and almost completely occluded the vein. Therefore, these results suggest that OLE ethanolic extract can modify the extrinsic coagulation pathway as evidenced by the prolongation of PT and changes in thrombus morphology, enough to justify further research to evaluate its possible antithrombotic effects. PMID:23702352

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats.

PubMed

Ramírez-Farías, Carlett; Madrigal-Santillán, Eduardo; Gutiérrez-Salinas, José; Rodríguez-Sánchez, Nidia; Martínez-Cruz, Maricela; Valle-Jones, Ilse; Gramlich-Martínez, Ingrid; Hernández-Ceruelos, Alejandra; Morales-Gonzaléz, José A

2008-02-14

To investigate the effects of vitamins (A, C and E) on liver injury induced by ethanol administration during liver regeneration in rats. Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups (groups 1-5). During the experiment, animals of Group 1 drank only water. The other four groups (2-5) drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and bilirubin were measured colorimetrically. Lipid peroxidation (thiobarbituric-acid reactive substances, TBARS) both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. Compared with sham group, serum AST and ALT increased significantly under ethanol treatment (43% and 93%, respectively, with P < 0.05). Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group (3.1 +/- 0.4 g/dL vs 4.5 +/- 0.2 g/dL; P < 0.05). During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation (4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P < 0.05). In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins (C and E) treatment attenuated hepatic and plasma lipid peroxidation. Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.

Preparation of a collagen/polymer hybrid gel designed for tissue membranes. Part I: controlling the polymer-collagen cross-linking process using an ethanol/water co-solvent.

PubMed

Nam, Kwangwoo; Kimura, Tsuyoshi; Funamoto, Seiichi; Kishida, Akio

2010-02-01

The drawback with collagen/2-methacryloyloxyethyl phosphorylcholine (MPC) polymer hybrid gels (collagen/phospholipid polymer hybrid gels) prepared in alkaline morpholinoethane sulfonic acid (MES) aqueous solution is that the cross-linking rate between the polymer and the collagen is low. To solve this problem, ethanol has been adopted as the reaction solvent, to prevent 1-ethyl-3-(3-dimethylaminopropyl)-1-carbodiimide hydrochloride (EDC) hydrolysis. Alterations in the ethanol mole concentration changed the cross-linking rate between the MPC polymer and the collagen gel. Prevention of EDC hydrolysis is clearly observed; protonation of carboxyl groups implies that the ratio of ethanol to water should be controlled. The polymer shows signs of penetration into the collagen gel layer, thus forming a totally homogeneous phase gel. This affects the mechanical strength of the collagen gel, making the gel much stiffer and brittle with an increase in the swelling ratio, as compared with that prepared in MES buffer. However, it is possible to obtain a collagen/phospholipid polymer hybrid gel with a high polymer portion and the cross-linking rate can be successfully controlled.

Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial.

PubMed

Weinberg, Jordan A; Magnotti, Louis J; Fischer, Peter E; Edwards, Norma M; Schroeppel, Thomas; Fabian, Timothy C; Croce, Martin A

2008-01-01

Although benzodiazepines are the recommended first-line therapy for the prevention of alcohol withdrawal syndrome (AWS), the administration of intravenous ethanol as an alternative prophylactic agent persists in many surgical ICUs. Advocates of this therapy argue that ethanol provides effective prophylaxis against AWS without the excessive sedation observed with benzodiazepine therapy. No study to date, however, has compared the two therapies with regard to their sedative effects. The purpose of this study was to prospectively evaluate the efficacy of intravenous ethanol compared with benzodiazepines for the prevention of AWS with particular emphasis on the sedative effects of each therapy. During a 15-month period, trauma patients admitted to the ICU with a history of chronic daily alcohol consumption greater than or equal to five beverage equivalents per day were prospectively randomized to one of two 4-day prophylactic regimens: intravenous ethanol infusion (EtOH) versus scheduled-dose diazepam (BENZO). Patients were evaluated with the Riker sedation-agitation scale, a 7-point instrument for the subjective assessment of both sedation (1 = unarousable) and agitation (7 = dangerous agitation). According to protocol, regimens were titrated to achieve and maintain a Riker score of 4 (calm and cooperative). Deviation from a score of 4 during the course of treatment was compared between groups. Fifty patients met study criteria and were randomized after obtainment of informed consent (EtOH, n = 26; BENZO, n = 24). Overall, the EtOH group had a significantly greater proportion of patients who deviated from a score of 4 during the course of treatment (p = 0.020). In both groups, the majority of deviation from a score of 4 reflected periods of under-sedation rather than over-sedation. One patient in the EtOH group failed treatment, requiring diazepam and haloperidol for control of AWS symptoms as per protocol, whereas no patient in the BENZO group failed treatment (p = NS). Concerning the prophylaxis of AWS, intravenous ethanol offers no advantage over diazepam with respect to efficacy or adverse sedative effects. The purported benefit of intravenous ethanol as a prophylactic agent against AWS was not evident.

Intermittent high-dose ethanol exposures increase motivation for operant ethanol self-administration: possible neurochemical mechanism.

PubMed

Li, Zhimin; Zharikova, Alevtina; Vaughan, Cheryl H; Bastian, Jaime; Zandy, Shannon; Esperon, Leonardo; Axman, Elyssia; Rowland, Neil E; Peris, Joanna

2010-01-15

We investigated the neurochemical mechanism of how high-dose ethanol exposure may increase motivation for ethanol consumption. First, we developed an animal model of increased motivation for ethanol using a progressive ratio (PR) schedule. Sprague-Dawley rats were trained to administer 10% ethanol-containing gelatin or plain gelatin (on alternate weeks) in daily 30-min sessions under different fixed ratio (FR) and PR schedules. During FR schedules, rats self-administered about 1 g/kg ethanol, which was decreased to 0.4+/-0.03 g/kg under PR10. Rats then received four pairs of either 3 g/kg ethanol or saline injections during the weeks when the reinforcer was plain gelatin. During subsequent ethanol gel sessions, breakpoints and ethanol consumption rose 40% in the high-dose ethanol group by the fourth set of injections with no change in plain gel responding. Alterations in amino acids in the ventral striatum (VS) during PR10 responding for 10% ethanol gelatin and plain gelatin were measured using microdialysis sampling coupled with capillary electrophoresis and laser-induced fluorescence detection. There was greater release of taurine, glycine and glutamate in the NAC of the high-dose ethanol rats during 10% ethanol-containing gelatin responding, compared to the control rats or during plain gel responding. An increase in the release of glycine in this same brain region has recently been shown to be involved with anticipation of a reward. Thus, it appears that intermittent high-dose ethanol exposure not only increases motivation for ethanol responding but may also change neurotransmitter release that mediates anticipation of reinforcement, which may play a key role in the development of alcoholism. Copyright 2009 Elsevier B.V. All rights reserved.

Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide.

PubMed

Beckmann, Diego V; Carvalho, Fabiano B; Mazzanti, Cinthia M; Dos Santos, Rosmarini P; Andrades, Amanda O; Aiello, Graciane; Rippilinger, Angel; Graça, Dominguita L; Abdalla, Fátima H; Oliveira, Lizielle S; Gutierres, Jessié M; Schetinger, Maria Rosa C; Mazzanti, Alexandre

2014-05-17

The purpose of this study was to investigate whether the flavonoid quercetin can prevent alterations in the behavioral tests and of cholinergic neurotransmission in rats submitted to the ethidium bromide (EB) experimental demyelination model during events of demyelination and remyelination. Wistar rats were randomly distributed into four groups (20 animals per group): Control (pontine saline injection and treatment with ethanol), Querc (pontine saline injection and treatment with quercetin), EB (pontine 0.1% EB injection and treatment with ethanol), and EB+Querc (pontine 0.1% EB injection and treatment with quercetin). The groups Querc and Querc+EB were treated once daily with quercetin (50mg/kg) diluted in 25% ethanol solution (1ml/kg) and the animals of the control and EB groups were treated once daily with 25% ethanol solution (1ml/kg). Two stages were observed: phase of demyelination (peak on day 7) and phase of remyelination (peak on day 21 post-injection). Behavioral tests (beam walking, foot fault and inclined plane test), acetylcholinesterase (AChE) activity and lipid peroxidation in pons, cerebellum, hippocampus, hypothalamus, striatum and cerebral cortex were measured. The quercetin promoted earlier locomotor recovery, suggesting that there was demyelination prevention or further remyelination velocity as well as it was able to prevent the inhibition of AChE activity and the increase of lipidic peroxidation, suggesting that this compound can protect cholinergic neurotransmission. These results may contribute to a better understanding of the neuroprotective role of quercetin and the importance of an antioxidant diet in humans to provide benefits in neurodegenerative diseases such as MS. Copyright © 2014. Published by Elsevier Inc.

Rat pancreatic B-cells after chronic alcohol feeding. A morphometric and fine structural study.

PubMed

Koko, V; Todorović, V; Nikolić, J A; Glisić, R; Cakić, M; Lacković, V; Petronijević, L; Stojković, M; Varagić, J; Janić, B

1995-04-01

Quantitative analysis of the light microscopic and fine structure of rat islet B-cells was carried out in chronic alcoholism. Absolute pancreatic weight and volume were similar in groups C (control) and E (ethanol), but relative pancreatic weight in group E rat was decreased. The results for fasting blood glucose and insulin levels were similar in the two groups of animals. There was a significantly reduced total pancreatic islet volume in E rats. The total number of endocrine cells both per islet and per microns2 of islet was similar in the two groups of animals. The volume density and number of B-cells per islet and per microns2 of islet were not changed in ethanol-treated rats as compared with the control. On the other hand, diameter, surface area and volume of the B-cells and their nuclei were found to be statistically significantly decreased. Histological examination revealed that islet blood vessels were dilated in alcoholic rats. Over the 4-month period of ethanol intake a significant decrease in cell profile area, nuclear profile area and volume density of cytoplasmic granules and an increase in the profile area and volume density of endoplasmic reticulum occurred. The gross histological alteration seen in most B-cells of the ethanol-treated rats was irregularity of the nuclear envelope with deep invagination and with margination of heterochromatin and many empty granules or granules without clear electron dense crystals of insulin. The present results indicate some optical and structural abnormalities of B-cells in chronic alcoholism that may be related to cell dysfunction and may contribute, at least in part, to the endocrine pancreas functional disturbance.

Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin.

PubMed

Martínez Conesa, Cristina; Vicente Ortega, Vicente; Yáñez Gascón, M Josefa; Alcaraz Baños, Miguel; Canteras Jordana, Manuel; Benavente-García, Obdulio; Castillo, Julián

2005-08-24

Melanoma is one of the most frequently metastasizing malignant neoplasias. This study examines an experimental model of pulmonary metastasis and the B16F10 cell subline, highly metastatic in the lung. Antimetastatic effects of the flavonoids tangeretin, rutin, and diosmin were analyzed, and at the same time an analysis of the metastatic activity of ethanol was performed, considered to be necessary because it is used as a vehicle for administering the flavonoids. Lentini's model, which complements the macroscopic evaluation of nodule numbers by using a stereoscopic microscope and image analysis at the microscopic level, was used. The greatest reduction in the number of metastatic nodules (52%) was obtained with diosmin; similarly, the percentages of implantation, growth index, and invasion index (79.40, 67.44, and 45.23%, respectively), were all compared with those of the ethanol group, considered to be an effective control group. Rutin- and tangeretin-treated groups also showed reductions of the same index compared with the ethanol group. It would seem that structural factors would better explain these results and the antimetastatic activity of each flavonoid and the respective metabolites.

T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference.

PubMed

Brasser, Susan M; Norman, Meghan B; Lemon, Christian H

2010-05-01

Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5-15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste.

Alteration in G Proteins and Prolactin Levels in Pituitary After Ethanol and Estrogen Treatment

PubMed Central

Chaturvedi, Kirti; Sarkar, Dipak K.

2010-01-01

Background Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol’s mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine the changes in the pituitary levels of G proteins during the tumor development following alcohol and ethanol treatments. Methods Using ovariectomized Fischer-344 female rats, we have determined ethanol and estradiol actions at 2 and 4 weeks on pituitary weight and pituitary cell contents of prolactin, Gs. Gq11, Gi1, Gi2, and Gi3 proteins. Western blots were employed to measure protein contents. Results Ethanol increased basal and estradiol-enhanced wet weight and the prolactin content in the pituitary in a time-dependent manner. Chronic exposure of estradiol increased the levels of Gs protein in the pituitary. Unlike estradiol, ethanol exposure did not show significant effect on the basal level of Gs protein, but moderately increased the estradiol-induced levels of this protein. Estradiol exposure enhanced Gq11 protein levels in the pituitary after 2 and 4 weeks, while ethanol treatment failed to alter these protein levels in the pituitary in control-treated or estradioltreated ovariectomized rats. In the case of Gi1, estradiol but not ethanol increased the level of this protein at 4 weeks of treatment. However, estradiol and ethanol alone reduced the levels of both Gi2 and Gi3 proteins at 2 and 4 weeks of treatment. Ethanol also significantly reduced the estradiol-induced Gi2 levels at 4 weeks and Gi3 level at 2 and 4 weeks. Conclusions These results confirm ethanol’s and estradiol’s growth-promoting and prolactin stimulating actions on lactotropes of the pituitary and further provide evidence that ethanol and estradiol may control lactotropic cell functions by altering expression of specific group of G proteins in the pituitary. PMID:18336630

Postnatal choline supplementation selectively attenuates hippocampal microRNA alterations associated with developmental alcohol exposure.

PubMed

Balaraman, Sridevi; Idrus, Nirelia M; Miranda, Rajesh C; Thomas, Jennifer D

2017-05-01

Prenatal alcohol exposure can result in a range of physical, neuropathological, and behavioral alterations, collectively termed fetal alcohol spectrum disorders (FASD). We have shown that supplementation with the nutrient choline reduces the severity of developmental alcohol-associated deficits in hippocampal-dependent behaviors and normalizes some aspects of hippocampal cholinergic development and DNA methylation patterns. Alcohol's developmental effects may also be mediated, in part, by altering microRNAs (miRNAs) that serve as negative regulators of gene translation. To determine whether choline supplementation alters ethanol's long-lasting effects on miRNAs, Sprague-Dawley rats were exposed to 5.25 g/kg/day ethanol from postnatal days (PD) 4-9 via intubation; controls received sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) or saline vehicle subcutaneously (s.c.) from PD 4-21. On PD 22, subjects were sacrificed, and RNA was isolated from the hippocampus. MiRNA expression was assessed with TaqMan Human MicroRNA Panel Low-Density Arrays. Ethanol significantly increased miRNA expression variance, an effect that was attenuated with choline supplementation. Cluster analysis of stably expressed miRNAs that exceeded an ANOVA p < 0.05 criterion indicated that for both male and female offspring, control and ethanol-exposed groups were most dissimilar from each other, with choline-supplemented groups in between. MiRNAs that expressed an average 2-fold change due to ethanol exposure were further analyzed to identify which ethanol-sensitive miRNAs were protected by choline supplementation. We found that at a false discovery rate (FDR)-adjusted criterion of p < 0.05, miR-200c was induced by ethanol exposure and that choline prevented this effect. Collectively, our data show that choline supplementation can normalize disturbances in miRNA expression following developmental alcohol exposure and can protect specific miRNAs from induction by ethanol. These findings have important implications for the mechanisms by which choline may serve as a potential treatment for FASD. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of the antimicrobial efficacy of povidone-iodine, povidone-iodine-ethanol and chlorhexidine gluconate-ethanol surgical scrubs.

PubMed

Nishimura, Chieko

2006-01-01

Scrubbing of the hands and forearms with a brush and antiseptic agents has been the standard for surgical practice. However, it has been increasingly recognized that brush scrubbing may provoke side effects and that an alcohol-based hand antiseptic used in conjunction with a scrub agent enhances the effectiveness. In this study, two types of alcohol-based agents were used after a povidone-iodine (PVP-I) scrub and compared for their effectiveness. The study was conducted as a crossover trial with 20 volunteers. After hand rubbing with PVP-I, either PVP-I-ethanol rubbing or chlorhexidine gluconate-ethanol (CHG-ethanol) rubbing was used for surgical hand cleansing. Samples were collected by the modified glove juice method to count bacteria on hands. In both groups, the bacterial count was significantly reduced after handwashing (p < 0.001), and the reduction was still significant after 2 h (p < 0.001 for PVP-I-ethanol and p < 0.002 for CHG-ethanol). The log(10) reduction factor (RF) in the PVP-I-ethanol group was significantly higher than that in the CHG-ethanol group immediately after handwashing (p < 0.001) but significantly lowered after 2 h (p < 0.01) to the level similar to that of CHG-ethanol. Although RF was lower in the CHG-ethanol group immediately after and 2 h after handwashing compared to the PVP-I-ethanol group, it did not decrease with time. Brushless surgical scrubbing with PVP-I-ethanol or CHG-ethanol in conjunction with PVP-I showed antiseptic effects immediately after and 2 h after handwashing. RF immediately after handwashing was significantly higher with PVP-I-ethanol compared to CHG-ethanol, but it was similar in both groups after 2 h. These results suggest that when used in combination with a PVP-I scrub, an alcohol-based hand antiseptic containing the same active agent (PVP-I in this study) has a powerful antiseptic effect; however, when it contains different antiseptic agents (i.e. CHG in this study), it should be selected carefully based on its antiseptic property.

Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Soo Kwang; Poet, Torka S.; Smith, Jordan N.

Chlorpyrifos (CPF) is one of the most studied and widely used broad spectrum organophosphorus (OP) insecticides. The neurotoxicity of CPF results from inhibition of cholinesterase (ChE) by its metabolite, chlorpyrifos-oxon (CPF-oxon), which subsequently leads to cholinergic hyperstimulation. The routine consumption of alcoholic beverages and tobacco products will modify a number of metabolic and physiological processes which may impact the metabolism and pharmacokinetics of other xenobiotics including pesticides. The objective of this study was to evaluate the influence of repeated ethanol and nicotine co-exposure on in vivo CPF pharmacokinetics and pharmacodynamics. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urinemore » along with changes in plasma and brain AChE activities were measured in male Sprague-Dawley (S-D) rats. Animals were repeatedly treated with either saline or ethanol (1 g/kg/day, po) and nicotine (1 mg/kg/day, sc) in addition to CPF (1 or 5 mg/kg/day, po) for 7 days. Rats were sacrificed at times from 1 to 24 hr post-last dosing of CPF. There were apparent differences in blood TCPy pharmacokinetics following ethanol and nicotine pretreatments in both CPF dose groups, which showed higher TCPy peak concentrations and increased blood TCPy AUC in ethanol and nicotine groups over CPF-only (~1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain acetylcholinesterase (AChE) activities from both ethanol and nicotine-treated groups showed substantially less inhibition following repeated 5 mg CPF/kg dosing compared to CPF-only controls (96 ± 13 and 66 ± 7% of naïve at 4 hr post-last CPF dosing, respectively). Inhibition of brain AChE activities was minimal in both 1 mg CPF/kg/day dosing groups, but a similar trend indicating less inhibition following ethanol/nicotine pretreatment was apparent. No differences were observed in plasma ChE activities due to the combined alcohol and nicotine treatments. In vitro, CPF metabolism was not affected by repeated treatments with ethanol or both ethanol and nicotine. When compared with a previous study of nicotine and CPF exposure, there were no apparent additional exacerbating effects due to ethanol co-exposure.« less

Histological investigation of the effect of soybean (Glycine max) extracts on the collagen layer and estrogen receptors in the skin of female rats

PubMed Central

Uyar, Belkiz; Sivrikoz, Oya Nermin; Ozdemir, Ugur; Dasbasi, Teslima; Sacar, Handan

2014-01-01

OBJECTIVES: The purpose of this study was to analyze the effects of soybean extracts obtained using different extraction methods on the skin of female rats. METHOD: A total of 64 female Sprague-Dawley rats were divided into 8 equal groups. Various extracts were administered to the female rats by oral gavage for one month. The groups comprised carboxymethyl cellulose-free control, carboxymethyl cellulose-plus control, 100-mg/kg n-hexane extract, 200-mg/kg n-hexane extract, 100-mg/kg ethyl acetate extract, 200-mg/kg ethyl acetate extract, 100-mg/kg ethanol extract and 200-mg/kg ethanol extract groups. The thickness of the collagen layer and the number of estrogen receptor-positive cells were evaluated. RESULTS: All the extract-treated groups showed a statistically significant decrease in the number of estrogen receptor-positive cells compared with the control groups. Regarding the thickness of the collagen layer, only the 200-mg/kg ethyl acetate extract-treated group showed a significant increase compared with the control groups (p<0.05). CONCLUSIONS: Our data suggest that oral intake of three different total soybean extracts might have positive estrogenic effects on the skin and that only a high-dose ethyl acetate extract can increase the expression of collagen, which may prove to be beneficial for postmenopausal facial skin. PMID:25627999

Effect of ethanolic extract of Carpolobia lutea G. Don (polygalaceae) root on learning and memory in CD1 mice.

PubMed

Ajiwhen, I O; Bisong, S A

2013-12-20

Carpolobia lutea, commonly called cattle stick or poor man's candle, is used by traditional herbalists in eastern Nigeria to treat 'madness'. It has a reported analgesic and anti-nociceptive effect. The effect of its ethanolic root extract on learning and memory was investigated. Thirty mice were divided into three groups of ten each. One group of mice served as the control and was given normal saline (p.o.) while the other two groups were given acute low dose (1500mg/kg, p.o.) and high dose (2500mg/kg, p.o.) (LD50 3338.83mg/kg). The effect of the extract on cognitive memory was investigated using the Novel Object recognition task (NORT) while the effect on visuospatial learning and memory was studied using the Morris Water maze (MWM). The results obtained in the NORT show that the index of habituation was significantly lower following acute treatment with a low dose of C. lutea extract compared to control. However, the index of habituation did not differ following treatment with a high dose of C. lutea compared to control but it was higher compared to the low dose. Following treatment with a low dose of the extract, the index of discrimination was significantly higher compared to control. The index of discrimination in the high dose treatment group did not differ from control, but it was lower compared to the low dose treatment. This indicated that there was improved cognitive memory only in the low dose treatment group. In the MWM there was no significant difference in swim latency during Acquisition and Reversal training. There also was no significant difference in quadrant duration during probe trial. The swim latency during the visible platform test showed that all mice used had good visual acuity. Therefore, the ethanolic extract of C. lutea root enhanced cognitive memory. However it did not affect visuospatial learning and memory.

Therapeutic role of Cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity.

PubMed

Aruna, K; Rukkumani, R; Varma, P Suresh; Menon, Venugopal P

2005-05-01

Ethanol is one of the most widely used and abused drugs, increasing lipid levels in humans and experimental animals. Heating of oil rich in polyunsaturated fatty acids (PUFA) produces various lipid peroxidative end products that can aggravate the pathological changes produced by ethanol. In the present communication, the effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced hyperlipidaemia. The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of rats given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in rats groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats. The levels were decreased when cumin was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of groups given alcohol, thermally oxidized oil and alcohol+thermally oridized oil when compared with the normal control rats. The level increased when cumin was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats, whereas the activity was decreased with the cumin treatment. The results obtained indicate that cumin can decrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity. Copyright (c) 2005 John Wiley & Sons, Ltd.

Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats.

PubMed

Alwahsh, Salamah Mohammad; Xu, Min; Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

2014-01-01

Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (≤3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial β-oxidation of fatty acids (Cpt1α and Ppar-α expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage.

Ameliorative Activity of Ethanol Extract of Artocarpus heterophyllus Stem Bark on Pancreatic β-Cell Dysfunction in Alloxan-Induced Diabetic Rats

PubMed Central

Ajiboye, Basiru O.; Ojo, Oluwafemi A.; Adeyonu, Oluwatosin; Imiere, Oluwatosin D.; Fadaka, Adewale O.; Osukoya, Adetutu O.

2016-01-01

This study sought to investigate the ameliorative effects of ethanol extract Artocarpus heterophyllus (EAH) in alloxan-induced diabetic rats. The rats were divided into 6 groups, with groups 1 and 2 serving as nondiabetic and diabetic control, respectively; group 3 serving as diabetic rats treated with 5 mg/kg glibenclamide; and groups 4 to 6 were diabetic rats treated with 50, 100, and 150 mg/kg of EAH, respectively. Assays determined were serum insulin, lipid peroxidation, and antioxidant enzyme activities. EAH stem bark reduced fasting blood glucose and lipid peroxidation levels and increased serum insulin levels and activities of antioxidant enzymes. Data obtained demonstrated the ability of EAH stem bark to ameliorate pancreatic β-cell dysfunction in alloxan-induced diabetic rats. PMID:29279019

Ameliorative Activity of Ethanol Extract of Artocarpus heterophyllus Stem Bark on Pancreatic β-Cell Dysfunction in Alloxan-Induced Diabetic Rats.

PubMed

Ajiboye, Basiru O; Ojo, Oluwafemi A; Adeyonu, Oluwatosin; Imiere, Oluwatosin D; Fadaka, Adewale O; Osukoya, Adetutu O

2017-10-01

This study sought to investigate the ameliorative effects of ethanol extract Artocarpus heterophyllus (EAH) in alloxan-induced diabetic rats. The rats were divided into 6 groups, with groups 1 and 2 serving as nondiabetic and diabetic control, respectively; group 3 serving as diabetic rats treated with 5 mg/kg glibenclamide; and groups 4 to 6 were diabetic rats treated with 50, 100, and 150 mg/kg of EAH, respectively. Assays determined were serum insulin, lipid peroxidation, and antioxidant enzyme activities. EAH stem bark reduced fasting blood glucose and lipid peroxidation levels and increased serum insulin levels and activities of antioxidant enzymes. Data obtained demonstrated the ability of EAH stem bark to ameliorate pancreatic β-cell dysfunction in alloxan-induced diabetic rats.

The selective kappa-opioid receptor agonist U50,488H attenuates voluntary ethanol intake in the rat.

PubMed

Lindholm, S; Werme, M; Brené, S; Franck, J

2001-05-01

Non-selective opioid receptor antagonists are increasingly used in the treatment of alcohol dependence. The clinical effects are significant but the effect size is rather small and unpleasant side effects may limit the benefits of the compounds. Ligands acting at mu- and/or delta- receptors can alter the voluntary intake of ethanol in various animal models. Therefore, the attenuating effects of selective opioid receptor ligands on ethanol intake may be of clinical interest in the treatment of alcoholism. The objective of this study was to examine the effects of a selective kappa-receptor agonist, U50,488H on voluntary ethanol intake in the rat. We used a restricted access model with a free choice between an ethanol solution (10% v/v) and water. During the 3-days baseline period, the rats received a daily saline injection (1 ml/kg, i.p.) 15 min before the 2 h access to ethanol. The animals had free access to water at all times. The control group received a daily saline injection during the 4-days treatment-period, whereas the treatment groups received a daily dose of U50,488H (2.5, 5.0 or 10 mg/kg per day). Animals treated with U50,488H dose-dependently decreased their ethanol intake. The effect of the highest dose of U50,488H was reduced by pre-treatment with the selective kappa-antagonist nor-binaltorphimine (nor-BNI). These results demonstrate that activation of kappa-opioid receptors can attenuate voluntary ethanol intake in the rat, and the data suggest that the brain dynorphin/kappa-receptor systems may represent a novel target for pharmacotherapy in the treatment of alcohol dependence.

Alpha-Tocopherol Supplementation Restricts Aluminium- and Ethanol-Induced Oxidative Damage in Rat Brain but Fails to Protect Against Neurobehavioral Damage.

PubMed

Nayak, Prasunpriya; Sharma, Shiv Bhushan; Chowdary, N V S

2018-04-05

The concurrent presence of oxidative stress (OS) and aluminium exposure is an inducer of neurodegenerative changes. Aluminium can augment OS in a pro-oxidant dominant condition. Antioxidative property of α-tocopherol may be useful in restricting these degenerative changes in the brain. OS parameters are tested in frontal cortex (FC), hippocampus (HC), and cerebellum (CL) of α-tocopherol-supplemented (5 IU/day) male Wistar rats exposed to aluminium (10 mg Al/Kg/day; "Al"), ethanol (0.6 g ethanol/Kg/day; "Et"), and both ("Al-Et") and vehicle-treated control ("C") for 4 weeks. The α-tocopherol supplementation restricted regional alterations of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Accordingly, the regional superoxide and peroxide handling capacities (SPHC) also remain unaltered. Al-Et group demonstrated significant elevation in the lipid peroxidation level in FC and CL regions compared to the group C; similar elevations in lipid peroxidation were noted in all the tested brain regions of Al group. Likewise, declines in glutathione reductase activity were noted in HC (versus Et group) and CL (versus Al and Et groups) of Al-Et group. Interestingly, changes in behavioral patterns of all the treatment groups are comparable while differing from that of the control group. Significant difference with group C is observed during first through fourth weeks, third to fourth weeks, and second to third weeks in terms of spontaneous motor activity, Rota Rod performance, and Hebb-Williams maze performance, respectively. Hence, the current dose and duration of α-tocopherol supplementation failed to provide full protection against the aluminium-induced neurodegeneration; nevertheless, it could provide only partial protection toward aluminium-induced augmentation of OS in specific brain regions.

Perinatal choline supplementation does not mitigate motor coordination deficits associated with neonatal alcohol exposure in rats.

PubMed

Thomas, Jennifer D; O'Neill, Teresa M; Dominguez, Hector D

2004-01-01

Prenatal alcohol exposure can disrupt brain development, leading to a variety of behavioral alterations including learning deficits, hyperactivity, and motor dysfunction. We have been investigating the possibility that perinatal choline supplementation may effectively reduce the severity of alcohol's adverse effects on behavioral development. We previously reported that perinatal choline supplementation can ameliorate alcohol-induced learning deficits and hyperactivity in rats exposed to alcohol during development. The present study examined whether perinatal choline supplementation could also reduce the severity of motor deficits induced by alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4 to 9 via an artificial rearing procedure. Artificially and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4 to 30, whereas the other half received saline vehicle injections. On PD 35-37, subjects were tested on a parallel bar motor task, which requires both balance and fine motor coordination. Ethanol-exposed subjects exhibited significant motor impairments compared to both control groups whose performance did not differ significantly from one another. Perinatal choline treatment did not affect motor performance in either ethanol or control subjects. These data indicate that the beneficial effects of perinatal choline supplementation in ethanol-treated subjects are task specific and suggest that choline is more effective in mitigating cognitive deficits compared to motor deficits associated with developmental alcohol exposure.

Influence of chronic ethanol consumption on toxic effects of 1,2-dichloroethane: glycolipoprotein retention and impairment of dolichol concentration in rat liver microsomes and Golgi apparatus.

PubMed

Cottalasso, Damiano; Domenicotti, Cinzia; Traverso, Nicola; Pronzato, Maria; Nanni, Giorgio

2002-09-16

Our previous investigations demonstrated that 1,2-dichloroethane (DCE) and chronic ethanol treatment separately are able to impair glycoprotein metabolism and secretion, and reduce dolichol concentration in liver membranes. The purpose of this study was to investigate whether chronic ethanol consumption can induce potentiation of rat liver damage due to DCE haloalkane used in several chemical processes and in agriculture. Rats were given 36% of their total energy as ethanol in the Lieber-DeCarli liquid diet for 8 weeks (CH group). The pair-fed control group received an isocaloric amount of dextrine-maltose (PF group). "In vitro" experiments: the DCE (6.5 mM) treatment of isolated hepatocytes from CH rats enhanced glycoprotein retention and further reduced glycoprotein secretion and 14C-glucosamine incorporation compared to the hepatocytes from CH or from PF and DCE treated rats. "In vivo" experiments: a marked decrease of dolichol concentration in microsomes (in which dolichyl phosphate is rate-limiting for the initial glycosylation of protein) and in Golgi membranes (in which total dolichol is very important for membrane permeability, fluidity and vesicle fusion) was observed in CH rats acutely treated with 628 mg/kg bw of DCE (CH+DCE) compared with CH or PF+DCE treated rats. These data suggest that chronic ethanol consumption increases DCE liver toxicity by affecting protein glycosylation processes and impairing glycolipoprotein secretion, with a concomitant retention at the level of the Golgi apparatus.

Pharmacological Investigation of the Wound Healing Activity of Cestrum nocturnum (L.) Ointment in Wistar Albino Rats

PubMed Central

Nagar, Hemant Kumar; Srivastava, Amit Kumar; Srivastava, Rajnish; Kurmi, Madan Lal; Chandel, Harinarayan Singh; Ranawat, Mahendra Singh

2016-01-01

Objectives. The present study was aimed at investigating the wound healing effect of ethanolic extract of Cestrum nocturnum (L.) leaves (EECN) using excision and incision wound model. Methods. Wistar albino rats were divided into five groups each consisting of six animals; group I (left untreated) considered as control, group II (ointment base treated) considered as negative control, group III treated with 5% (w/w) povidone iodine ointment (Intadine USP), which served as standard, group IV treated with EECN 2% (w/w) ointment, and group V treated with EECN 5% (w/w) ointment were considered as test groups. All the treatments were given once daily. The wound healing effect was assessed by percentage wound contraction, epithelialization period, and histoarchitecture studies in excision wound model while breaking strength and hydroxyproline content in the incision wound model. Result. Different concentration of EECN (2% and 5% w/w) ointment promoted the wound healing activity significantly in both the models studied. The high rate of wound contraction (P < 0.001), decrease in the period for epithelialization (P < 0.01), high skin breaking strength (P < 0.001), and elevated hydroxyproline content were observed in animal treated with EECN ointments when compared to the control and negative control group of animals. Histopathological studies of the EECN ointments treated groups also revealed the effectiveness in improved wound healing. Conclusions. Ethanolic extract of Cestrum nocturnum (EECN) leaves possesses a concentration dependent wound healing effect. PMID:27018126

[Gastroprotective and antisecretory effect of a phytochemical made from matico leaves (Piper aduncum)].

PubMed

Arroyo, Jorge; Bonilla, Pablo; Moreno-Exebio, Luis; Ronceros, Gerardo; Tomás, Gloria; Huamán, Juana; Raez, Ernesto; Quino, Mariano; Rodriguez-Calzado, Javier

2013-01-01

To determine the gastroprotective and antisecretory effect of ethanol extract from matico leaves (Piper aduncum) in animal models. To evaluate the gastroprotective effect, 220 mice of the Balb C57 strain were used. They were randomized in 22 groups of ten animals each, in which the formation of gastric ulcers was induced with indomethacin. Gastroprotection was determined by evaluating three aspects: inflammation, number of hemorrhagic shocks and number of ulcers. To evaluate the antisecretory effect, 64 white male Holtzman rats were used, which were randomized in eight groups of eight animals, one control and seven groups of treatment with one extract dose level and two phytochemical dose levels. Antisecretion was obtained through the pylorus ligation. Regarding gastroprotection, dichloromethane, chloroform, hexane and methanol extracts decreased inflammation to over 66% (p<0,05). The ethanolic extract shows 100% activity in reducing the number of hemorrhagic bands (p<0,05). The chloroform extract shows antiulcer activity at 75% (p<0,05). In terms of antisecretion, the phytochemical in capsules containing the ethanolic extract achieved 72% reduction of the gastric secretion volume (p<0,01) and 104,3% (p<0,01) PH increase. In experimental conditions, ethanolic extracts, their fractions and phytochemicals have a gastroprotective effect in mice and antisecretory effect in rats.

Hepatoprotective effects of ethanol extracts from Folium Syringae against acetaminophen-induced hepatotoxicity in vitro and in vivo.

PubMed

Shi, Chen-Xi; Lin, Yue-Xia; Liu, Fang-Ping; Chang, Yi-Cong; Li, Rui; Li, Chang-Wen; Li, Ying; He, Jing-Shan; Ma, Xin; Li, Zhi

2017-10-01

The leaves of Folium Syringae (FS) have been long used as a traditional Chinese folk medicine for their anti-inflammatory effect, utilized as an antibacterial and antiviral treatment. The purpose of this study was to investigate the potential hepatoprotective effects of FS on acetaminophen-induced hepatic injury in primary hepatocytes and mice. Hepatocytes obtained by the inverse perfusion method were divided randomly into five groups. Prior to acetaminophen exposure, 3 different doses of FS ethanol extracts were given to hepatocytes and mice, respectively. Thereafter, transaminases, glutathione S-transferase A1 (GSTA1) and some hepatic indices were determined. FS ethanol extracts (200 μg/mL) pretreatment prevented all of the alterations, returning their levels to nearly those levels observed in the control group in vitro. Treatment with FS ethanol extracts (200 mg/kg) significantly reduced the toxicity induced by acetaminophen in vivo, which manifested as a decrease in transaminases, and the hepatoprotective effects of FS were similar to Silymarin (positive group). GSTA1 represented the same change trend as transaminases and hepatic indices, and at a dose of 100 μg/mL FS ethanol extracts in vitro and 100 mg/kg in vivo, GSTA1 content changed significantly (p < 0.01), but transaminases were insignificant (p > 0.05). The results of our investigation suggested that FS ethanol extracts possess significant protective effects against hepatotoxicity induced by acetaminophen both in vitro and in vivo. In addition, GSTA1 could be used as an indicator assessing the extents of hepatic injury, which is more sensitive than transaminases. Copyright © 2017. Published by Elsevier Taiwan LLC.

Gastroprotective actions of Taraxacum coreanum Nakai water extracts in ethanol-induced rat models of acute and chronic gastritis.

PubMed

Yang, Hye Jeong; Kim, Min Jung; Kwon, Dae Young; Kang, Eun Seon; Kang, Suna; Park, Sunmin

2017-08-17

Taraxacum coreanum Nakai has been traditionally used for treating inflammatory diseases including gastrointestinal diseases. We studied whether water extracts of Taraxacum coreanum Nakai (TCN) had a protective effect on acute and chronic gastritis induced by ethanol/HCl in an animal model of gastritis and its mechanism was also explored. In the acute study, rats were orally administered 0.15g/mL dextrin (normal-control), 0.15g/mL dextrin (control), 0.05g/mL TCN (TCN-L), 0.15g/mL TCN (TCN-H), or 0.01g/mL omeprazole (orally; positive-control), followed by oral administration of 1mL of 60% ethanol plus 150mM HCl (inducer). In the chronic study, rats were administered 10% diluted inducer in drinking water, and 0.6% dextrin, 0.2% or 0.6% TCN, and 0.05% omeprazole were administered in chow for 4 weeks. Acid content, gastric structure, oxidative stress, and markers of inflammation in the stomach tissue were measured at the end of experiment. Acute and chronic ethanol/HCl administration caused the inner layer of the stomach to redden, hemorrhage, and edema in the control group; TCN-H reduced these symptoms more effectively than did the omeprazole positive-control. Acid production and total acidity in the stomach increased in the control group, which was markedly suppressed by omeprazole. TCN also reduced the acid production and acidity, but not to the same degree as omeprazole. H-E and PAS staining revealed that in the inner layer of the stomach, cellular structure was disrupted, with an increased nuclear size and thickness, disarrangement, and decreased mucin in the control group. TCN prevented the cellular disruption in the inner layer, and TCN-H was more effective than the positive-control. This was associated with oxidative stress and inflammation. TCN dose-dependently reduced the infiltration of mast cells and TNF-α expression in the inner layer of the stomach, and decreased lipid peroxides by increasing superoxide dismutase and glutathione peroxidase expression. TCN-H acutely and chronically protected against gastritis and gastric ulcer by reducing oxidative stress and inflammation, not by completely suppressing gastric acid production. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Efficacy of Trigonella foenum-graecum Seed Extract in Reducing Metabolic and Inflammatory Alterations Associated With Menopause

PubMed Central

Abedinzade, Mahmood; Nasri, Sima; Jamal Omodi, Masome; Ghasemi, Elham; Ghorbani, Ahmad

2015-01-01

Background: Several experimental and clinical studies support beneficial effects of Trigonella foenum-graecum (fenugreek) in the management of metabolic diseases and inflammatory disorders. Objectives: The purpose of this study was to examine the effect of T. foenum-graecum seed extract in reducing the metabolic and inflammatory alternations associated with menopause. Materials and Methods: In this experimental study, 49 rats were divided into seven groups: (I) sham-control, (II) ovariectomized-control, (III and IV) ovariectomized treated with 50 and 150 mg/kg of T. foenum-graecum seed ethanolic extract, (V and VI) ovariectomized treated with 50 and 150 mg/kg of T. foenum-graecum hexanic extract, (VII) ovariectomized-positive control treated with 10 µg/kg of estradiol. The extracts were injected intraperitoneally one day after ovariectomy and the treatments were lasted for 42 days. Results: Fasting blood glucose and body weight gain increased significantly in the ovariectomized-control group compared with that in the sham animals (P < 0.05). Administration of estradiol and T. foenum-graecum (50 and 150 mg/dL of hexanic extract and 150 mg/kg of ethanolic extract) significantly diminished the increase in glucose and body weight (P < 0.05). The serum level of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the ovariectomized control group was significantly higher than those in the sham animals (P < 0.05). Both hexanic and ethanolic extracts as well as estradiol were able to decrease level of these cytokines in the serum of ovariectomized rats (P < 0.05). Conclusions: The results of the present study show that administration of T. foenum-graecum corrects metabolic and inflammatory alterations associated with ovariectomy and has a potential for the management of menopause. PMID:26732240

[Plasma clearance of ethanol and its excretion in the milk of rural women who consume pulque].

PubMed

Argote-Espinosa, R M; Flores-Huerta, S; Hernández-Montes, H; Villalpando-Hernández, S

1992-01-01

Women from rural areas of the central plateau of Mexico drink during pregnancy and lactation a mild alcoholic beverage called pulque as a galactogogue. Ethanol present in milk could have a harmful effect on growth and development of breast-fed children. The purpose of this study was to quantify the ethanol consumed as pulque by eleven lactating rural women as well as its clearance rate in blood and milk. Mothers were separated in two groups depending upon the ethanol ingested in a single dose of pulque 0.21 +/- 0.08 g/kg of body weight (group A) and 0.44 +/- 0.11 g/kg (group B). Maximal concentration of ethanol was reached in milk at 60 minutes and almost equaled that in plasma. Both groups showed a similar clearance pattern regardless of the volume of pulque ingested. Clearance rates between groups were different: ethanol concentration in milk at 60 min were 8.4 +/- 3.0 mg/dL for group A and 26.2 +/- 7.0 mg/dL for group B. Two hours later ethanol levels were 3.6 +/- 3.4 mg/dL and 23.3 +/- 9.4 mg/dL respectively. Clearance rates were slower in mothers showing the highest concentration of ethanol in milk. The present data demonstrate that there is no differential elimination of ethanol in maternal blood and milk following ingestion of a moderate amount of pulque during lactation. The amount of ethanol received by infants through milk is relatively low and therefore it is unlikely to have harmful effects on them. Pulque consumption adds about 350 kcal/day to the customary dietary intake of these lactating women.

Alcohol, gestation and breastfeeding: selenium as an antioxidant therapy.

PubMed

Ojeda, Ma Luisa; Nogales, Fatima; Vázquez, Beatriz; Delgado, Ma José; Murillo, Ma Luisa; Carreras, Olimpia

2009-01-01

The aim of this paper is to study the relationship between alcohol, selenium and oxidative stress in breastfeeding rat pups exposed to ethanol during gestation and lactation. We have also studied how a Se-supplemented diet among mothers could prevent different oxidative liver disorders in the pups. Pups of 21 days were randomized into four groups: control group (C), alcohol group (A), alcohol selenium group (AS) and control selenium group (CS). Alcohol was supplied to their mothers for 13 weeks (induction, reproduction, gestation and lactation periods). The selenium-supplemented diet contained 0.5 ppm as selenite. We determined serum and liver selenium by graphite-furnace atomic absorption spectrometry. We measured antioxidant enzyme activities: glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD); and lipid peroxidation (TBARS) and protein carbonyl (PC) by a spectrophotometric method in the liver. In the liver of pups, exposure to ethanol provoked a decrease in selenium and GPx activity and an increase in GR and CAT activity, as well as in carbonyl groups in protein. A pups had higher Se levels and GPx activity in serum than C pups. Administering Se with alcohol balances the activities of scavenging enzymes and reduces peroxidation protein products. These results suggest that selenium could be effective in neutralizing the damage of ethanol consumption during gestation and lactation in pups since it repairs selenium levels in liver as well as the activity of scavenging enzymes and peroxidation protein products. In serum, Se also recovers GPx activity and increases the levels of Se that are available to other organs.

Autoshaping of ethanol drinking: an animal model of binge drinking.

PubMed

Tomie, Arthur; di Poce, Jason; Derenzo, Christopher C; Pohorecky, Larissa A

2002-01-01

To examine the hypothesis that Pavlovian autoshaping provides an animal learning model of drug abuse, two studies evaluated the induction of ethanol drinking by autoshaping procedures. In Experiment 1, the sipper tube conditioned stimulus (CS) contained saccharin/ethanol solution and was repeatedly paired with food as an unconditioned stimulus (US). The CS-US paired group consumed more of the 0.1% saccharin-6% ethanol solution than did the CS-US random group, revealing that autoshaping conditioned responses (CR) induce ethanol drinking not attributable to pseudo-conditioning. Experiment 2 employed saccharin-fading procedures and showed that the paired vs random group differences in ethanol drinking were maintained, even as the saccharin was eliminated from the solution. The results show that Pavlovian autoshaping procedures induce high volumes of ethanol drinking when the presentation of a sipper tube containing an ethanol solution precedes the response-independent delivery of food. The high volume of ethanol consumed in a brief period of time suggests that Pavlovian autoshaping may be a model of binge drinking.

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

PubMed Central

Ramírez-Farías, Carlett; Madrigal-Santillán, Eduardo; Gutiérrez-Salinas, José; Rodríguez-Sánchez, Nidia; Martínez-Cruz, Maricela; Valle-Jones, Ilse; Gramlich-Martínez, Ingrid; Hernández-Ceruelos, Alejandra; Morales-González, José A

2008-01-01

AIM: To investigate the effects of vitamins (A, C and E) on liver injury induced by ethanol administration during liver regeneration in rats. METHODS: Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups (groups 1-5). During the experiment, animals of Group 1 drank only water. The other four groups (2-5) drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and bilirubin were measured colorimetrically. Lipid peroxidation (thiobarbituric-acid reactive substances, TBARS) both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. RESULTS: Compared with sham group, serum AST and ALT increased significantly under ethanol treatment (43% and 93%, respectively, with P < 0.05). Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group (3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P < 0.05). During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation (4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P < 0.05). In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins (C and E) treatment attenuated hepatic and plasma lipid peroxidation. CONCLUSION: Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration. PMID:18240347

Prenatal Alcohol Exposure and Cellular Differentiation

PubMed Central

Veazey, Kylee J.; Muller, Daria; Golding, Michael C.

2013-01-01

Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell–cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell’s identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes—the Polycomb and Trithorax proteins—are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder. PMID:24313167

Hypoglycemic and hypolipidemic activity of ethanolic extract of Salvadora oleoides in normal and alloxan-induced diabetic rats

PubMed Central

Yadav, J.P.; Saini, Sushila; Kalia, A.N.; Dangi, A.S.

2008-01-01

Objective: To find out the hypoglycemic and hypolipidemic activity of an ethanolic extract of the aerial part of Salvadora oleoides Decne in euglycemic and alloxan-induced diabetic albino rats. Materials and Methods: Diabetes was induced in albino rats by administration of alloxan monohydrate (120 mg/kg, i.p.). Normal as well as diabetic albino rats were divided into groups (n = 6) receiving different treatments: vehicle (control), ethanolic extract (1 g and 2 g/kg b.w), and standard antidiabetic drug tolbutamide (0.5 g/kg b.w.). Blood samples were collected by cardiac puncture and were analyzed for blood glucose and lipid profile on days 0, 7, 14, and 21. Results: The ethanolic extract of S oleoides produced significant reduction (P < 0.001) in blood glucose and also had beneficial effects (P < 0.001) on the lipid profile in euglycemic as well as alloxan-induced diabetic rats at the end of the treatment period (21st day). However, the reduction in the blood glucose and improvement in lipid profile was less than that achieved with the standard drug tolbutamide. Conclusion: We concluded that an ethanolic extract of S oleoides is effective in controlling blood glucose levels and improves lipid profile in euglycemic as well as diabetic rats. PMID:21264157

Spermatoprotective activity of the leaf extract of Psidium guajava Linn.

PubMed

Akinola, O B; Oladosu, O S; Dosumu, O O

2007-12-01

The leaves of Psidium guajava Linn. (guava) contain several natural antioxidants. We therefore designed the present study to evaluate the effect of ethanol extract of guava leaves on gossypol-associated sperm toxicity in Wistar rats. Animal groups 1, 2, and 3 (n=6 each) were treated orally with crude cottonseed oil to provide 14 mg/kg/d of free gossypol for 53 d. Besides, groups 1 and 2 rats were supplemented orally with 250 mg/kg/d and 500 mg/kg/d respectively of guava leaf extract (GLE) for the same period. Group 4 animals (control, n=6) received normal saline. No significant difference (P>0.05) occurred in the sperm count of group 1 rats compared to control. In animal group 2, significant increase (P<0.05) in sperm count occurred, as opposed to group 3 animals, where this parameter decreased significantly (P<0.05). Besides, mean values of 78 %, 82 %, 30 %, and 65 % respectively were obtained for sperm motility in animal groups 1, 2, 3, and 4. Our findings suggest that ethanol extract of guava leaves possesses beneficial effect on gossypol-associated sperm toxicity, and may therefore enhance male fertility, possibly owing to its rich constituents of natural antioxidants.

Agmatine blocks ethanol-induced locomotor hyperactivity in male mice.

PubMed

Ozden, Onder; Kayir, Hakan; Ozturk, Yusuf; Uzbay, Tayfun

2011-05-20

Ethanol-induced locomotor activity is associated to rewarding effects of ethanol and ethanol dependence. Agmatine is a novel endogenous ligand at α2-adrenoceptors, imidazoline and N-methyl-d-aspartate (NMDA) receptors, as well as a nitric oxide synthase (NOS) inhibitor. There is no evidence presented for the relationship between the acute locomotor stimulating effect of ethanol and agmatine. Thus, the present study investigated the effects of agmatine on acute ethanol-induced locomotor hyperactivity in mice. Adult male Swiss-Webster mice (26-36g) were used as subjects. Locomotor activity of the mice was recorded for 30min immediately following intraperitoneal administration of ethanol (0.5, 1 and 2g/kg) or saline (n=8 for each group). Agmatine (5, 10 and 20mg/kg) or saline was administered intraperitoneally to another four individual groups (n=8 for each group) of the mice 20min before the ethanol injection. In these groups, locomotor activity was also recorded immediately following ethanol (0.5g/kg) injection for 30min. Ethanol (0.5g/kg) produced some significant increases in locomotor activity of the mice. Agmatine (5-20mg/kg) significantly blocked the ethanol (0.5g/kg)-induced locomotor hyperactivity. These doses of agmatine did not affect the locomotor activity in naive mice when they were administered alone. Our results suggest that agmatine has an important role in ethanol-induced locomotor hyperactivity in mice. There may be a relationship between the addictive psychostimulant effects of the ethanol and central agmatinergic system. Copyright © 2011 Elsevier B.V. All rights reserved.

Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice

PubMed Central

Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Taguchi, Takehito

2017-01-01

ABSTRACT Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury. PMID:28498931

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Zhengqi

Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showedmore » a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. - Highlights: • Glucocorticoid but not ethanol enhanced the expression of OPG in chondrocytes. • PEE reduced osteoclast differentiation relative with over-expression of OPG. • PEE inhibited endochondral ossification in fetal long bones of rats. • Endochondral ossification delay is regarded as the thrifty phenotype induced by PEE.« less

Effects of postnatal ethanol exposure at different developmental phases on neurotrophic factors and phosphorylated proteins on signal transductions in rat brain.

PubMed

Tsuji, Ryozo; Fattori, Vittorio; Abe, Shin-ichi; Costa, Lucio G; Kobayashi, Kumiko

2008-01-01

Exposure to ethanol during development induces severe brain damage resulting in a number of CNS dysfunctions including microencephaly and mental retardation in humans and in laboratory animals. The most vulnerable period to ethanol neurotoxicity coincides with the peak of brain growth spurt. Recently, neurotrophic factors and/or their signal transduction pathways have been reported as a potential relevant target for the developmental neurotoxicity of ethanol. The present studies were designed to investigate the effects of ethanol given in various developmental phases during the brain growth spurt in rats. Rat pups were assigned to the three treatment groups and treated with 5 g/kg of ethanol for three days, on postnatal days (PND) 2-4, 6-8 or 13-15. Whole brain weights were reduced only in the PND 6-8 group concurrently with the reduction of GDNF mRNA in cortex in this group. BDNF mRNA expression was reduced in both the PND 6-8 and 13-15 groups, while mRNA expressions of NT-3 and NGF were unchanged in all three groups. Phospho-Akt level was mostly reduced in the PND 6-8 group. Both phospho-MAPK and p-70S6 kinase levels were decreased in all groups whereas no changes were observed in either phospho-PKCzeta or CREB level. The phosphorylation of Akt was immediately inhibited after single administration of ethanol, and its inhibition was correlated with variations in blood ethanol concentration. These findings suggest that GDNF and the phosphorylation of Akt play a possible key role in the ethanol-induced developmental neurotoxicity.

Immunolocalization of androgen and oestrogen receptors in the ventral lobe of rat (Rattus norvegicus) prostate after long-term treatment with ethanol and nicotine.

PubMed

Fávaro, W J; Cagnon, V H A

2008-12-01

Nicotine and alcohol adversely affect prostate gland function. In this work, immunohistochemistry was used to investigate the immunoreactivity and distribution of androgen and alpha, beta-oestrogen receptors following chronic treatment with alcohol, nicotine or a combination of both substances, as well as to relate these results to the development of possible prostatic pathologies. Forty male rats were divided into four groups: the Control group received tap water; the Alcoholic group received diluted 10% Gay Lussac ethanol; the Nicotine group received a 0.125 mg/100 g body weight dose of nicotine injected subcutaneously on a daily basis (Sigma Chemical Company, St. Louis, MO, USA); the Nicotine-Alcohol group received simultaneous alcohol and nicotine treatment. After 90 days of treatment, samples of the ventral lobe of the prostate were collected and processed for immunohistochemistry, light microscopy and the quantification of serum hormonal concentrations. The results showed significantly decreased serum testosterone levels and increased serum oestrogen levels in the animals from the nicotine-alcohol, the alcoholic and the nicotine groups, as well as their hormonal receptor levels. Then, it was concluded that ethanol and nicotine compromised the prostatic hormonal balance, which is a crucial factor to maintain the morphological and physiological features of this organ.

Ethanol drinking reduces extracellular dopamine levels in the posterior ventral tegmental area of nondependent alcohol-preferring rats.

PubMed

Engleman, Eric A; Keen, Elizabeth J; Tilford, Sydney S; Thielen, Richard J; Morzorati, Sandra L

2011-09-01

Moderate ethanol exposure produces neuroadaptive changes in the mesocorticolimbic dopamine (DA) system in nondependent rats and increases measures of DA neuronal activity in vitro and in vivo. Moreover, moderate ethanol drinking and moderate systemic exposure elevates extracellular DA levels in mesocorticolimbic projection regions. However, the neuroadaptive changes subsequent to moderate ethanol drinking on basal DA levels have not been investigated in the ventral tegmental area (VTA). In the present study, adult female alcohol-preferring (P) rats were divided into alcohol-naive, alcohol-drinking, and alcohol-deprived groups. The alcohol-drinking group had continuous access to water and ethanol (15%, vol/vol) for 8 weeks. The alcohol-deprived group had 6 weeks of access followed by 2 weeks of ethanol deprivation, 2 weeks of ethanol re-exposure, followed again by 2 weeks of deprivation. The deprived rats demonstrated a robust alcohol deprivation effect (ADE) on ethanol reinstatement. The alcohol-naïve group had continuous access to water only. In the last week of the drinking protocol, all rats were implanted with unilateral microdialysis probes aimed at the posterior VTA and no-net-flux microdialysis was conducted to quantify extracellular DA levels and DA clearance. Results yielded significantly lower basal extracellular DA concentrations in the posterior VTA of the alcohol-drinking group compared with the alcohol-naive and alcohol-deprived groups (3.8±0.3nM vs. 5.0±0.5nM [P<.02] and 4.8±0.4nM, [P<.05], respectively). Extraction fractions were significantly (P<.0002) different between the alcohol-drinking and alcohol-naive groups (72±2% vs. 46±4%, respectively) and not significantly different (P=.051) between alcohol-deprived and alcohol-naive groups (61±6% for the alcohol-deprived group). The data indicate that reductions in basal DA levels within the posterior VTA occur after moderate chronic ethanol intake in nondependent P rats. This reduction may result, in part, from increased DA uptake and may be important for the maintenance of ethanol drinking. These adaptations normalize with ethanol deprivation and may not contribute to the ADE. Copyright © 2011 Elsevier Inc. All rights reserved.

Prenatal Ethanol Exposure Causes Glucose Intolerance with Increased Hepatic Gluconeogenesis and Histone Deacetylases in Adult Rat Offspring: Reversal by Tauroursodeoxycholic Acid

PubMed Central

Yao, Xing-Hai; Nguyen, Hoa K.; Nyomba, B. L. Grégoire

2013-01-01

Prenatal ethanol exposure results in increased glucose production in adult rat offspring and this may involve modulation of protein acetylation by cellular stress. We used adult male offspring of dams given ethanol during gestation days 1–7 (early), 8–14 (mid) and 15–21 (late) compared with those from control dams. A group of ethanol offspring was treated with tauroursodeoxycholic acid (TUDCA) for 3 weeks. We determined gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, hepatic free radicals, histone deacetylases (HDAC), acetylated foxo1, acetylated PEPCK, and C/EBP homologous protein as a marker of endoplasmic reticulum stress. Prenatal ethanol during either of the 3 weeks of pregnancy increased gluconeogenesis, gluconeogenic genes, oxidative and endoplasmic reticulum stresses, sirtuin-2 and HDAC3, 4, 5, and 7 in adult offspring. Conversely, prenatal ethanol reduced acetylation of foxo1 and PEPCK. Treatment of adult ethanol offspring with TUDCA reversed all these abnormalities. Thus, prenatal exposure of rats to ethanol results in long lasting oxidative and endoplasmic reticulum stresses explaining increased expression of gluconeogenic genes and HDAC proteins which, by deacetylating foxo1 and PEPCK, contribute to increased gluconeogenesis. These anomalies occurred regardless of the time of ethanol exposure during pregnancy, including early embryogenesis. As these anomalies were reversed by treatment of the adult offspring with TUDCA, this compound has therapeutic potentials in the treatment of glucose intolerance associated with prenatal ethanol exposure. PMID:23544086

The protective activity of Conyza blinii saponin against acute gastric ulcer induced by ethanol.

PubMed

Ma, Long; Liu, Jiangguang

2014-12-02

Conyza blinii H.Lév., is a type of natural plant. Its dried overground section is used to treat infections and inflammations in traditional Chinese medicine. Triterpenoidal saponins have a wide range of bioactivities, for instance, anti-cancer, anti-virus and anti-anaphylaxis. Conyza blinii saponin (CBS), mainly composed of triterpenoidal saponins, is the total saponin of Conyza blinii H.Lév. It has been reported that CBS also has gastric mucous membrane protection activity. This study aims to test CBS׳s protective activity of gastric׳s mucous membrane against ethanol. This investigation may lead to the development of novel drug from natural products as anti-ulcer agent, or as gastric mucous protective against chemical damage. CBS (Conyza blinii saponin) is the total saponin of Conyza blinii H.Lév., which was obtained as described previously. We tested the protective activity of CBS against ethanol-induced ulcer. Thirty six rats were grouped randomly as 'NORMAL', 'CONTROL', 'MODEL', 'LOW DOSE', 'MEDIUM DOSE' and 'HIGH DOSE'. The 'NORMAL' group were rats with no pathological model established within it. The 'CONTROL' group was administrated with colloidal bismuth subcitrate, while 'MODEL' group was not given any active agents apart from absolute ethanol in order to obtain gastric ulcer model. The three 'DOSE' groups were treated with different concentrations of CBS (5, 10, 20mg/mL) before administration followed by absolute ethanol. All rats were sacrificed after the experiment to acquire the gastric tissue. The ulcer index (UI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to monitor the activity of CBS. Besides, the rat gastric tissue was made to paraffin section and stained using the Hematoxylin-Eosin (HE) method. The histopathology examination was carried out to examine CBS efficacy in terms of gastric mucous protection. We found that CBS had a profound protection activity against acute gastric ulcer induced by ethanol and this activity displayed a concentration-dependent manner. The efficacy of 10 and 20mg/mL CBS was comparable with colloidal bismuth subcitrate (P<0.05). All three level of CBS tested were able to significantly reduce UI, MDA and enhance SOD level (P<0.05). It was deduced that the mechanism for such activity would be anti-lipid peroxidation, facilitating free radicals clearance. In addition , histopathology examination of the gastric mucous membrane supported the same conclusion, that CBS can efficiently suppress the inflammatory reactions, bleeding and protect the gastric mucosa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Amelioration of Ethanol-Induced Gastric Ulcers in Rats Pretreated with Phycobiliproteins of Arthrospira (Spirulina) Maxima.

PubMed

Guzmán-Gómez, Oscar; García-Rodríguez, Rosa Virginia; Quevedo-Corona, Lucía; Pérez-Pastén-Borja, Ricardo; Rivero-Ramírez, Nora Lilia; Ríos-Castro, Emmanuel; Pérez-Gutiérrez, Salud; Pérez-Ramos, Julia; Chamorro-Cevallos, Germán Alberto

2018-06-13

Phycobiliproteins of Arthrospira ( Spirulina ) maxima have attracted attention because of their potential therapeutic antioxidant properties. The aim of this study was to assess the possible antiulcerogenic activity of these phycobiliproteins (ExPhy) against ethanol-induced gastric ulcers in rats. To explore the possible mechanisms of action, we examined antioxidant defense enzymes (e.g., catalase, superoxide dismutase, and glutathione peroxidase), as well as the level of lipid peroxidation (MDA) and the histopathological changes in the gastric mucosa. Intragastric administration of ExPhy (100, 200, and 400 mg/kg body weight) significantly lowered the ulcer index value compared to the ulcer control group ( p < 0.05). The greatest protection was provided by the concentration of 400 mg/kg. The histological study supported the observed gastroprotective activity of ExPhy, showing a reduced inflammatory response. Moreover, the alcohol-induced decrease in stomach antioxidant enzyme activity found in the ulcer control group was prevented by ExPhy pretreatment. Furthermore, ExPhy reversed the ethanol-induced increase in lipid peroxidation. In summary, the antiulcerogenic potential of ExPhy may be due, at least in part, to its anti-oxidant and anti-inflammatory effects.

Enhanced Sensitivity to Attenuation of Conditioned Reinstatement by the mGluR2/3 Agonist LY379268 and Increased Functional Activity of mGluR2/3 in Rats with a History of Ethanol Dependence

PubMed Central

Kufahl, Peter R; Martin-Fardon, Rémi; Weiss, Friedbert

2011-01-01

Recent findings implicate group II metabotropic glutamate receptors (mGluR2/3) in the reinforcing and dependence-inducing actions of ethanol and identify these receptors as treatment targets for alcoholism. Here, we investigated the effects of mGLuR2/3 activation on conditioned reinstatement in rats with different ethanol-dependence histories and examined dependence-associated changes in the functional activity of mGluR2/3. Following ethanol self-administration training and conditioning procedures, rats were made ethanol dependent, using ethanol vapor inhalation, under three conditions: a single intoxication and withdrawal episode (SW), repeated cycles of intoxication and withdrawal (RW), or no intoxication (CTRL). At 1 week after removal from ethanol vapor, self-administration resumed until stable baseline performance was reached, followed by extinction of operant responding and reinstatement tests. Post-withdrawal self-administration was increased in the RW group, but all groups showed conditioned reinstatement. The mGluR2/3 agonist LY379268 dose -dependently reduced reinstatement in all groups, but was more effective at low doses in the SW and RW groups. The highest dose of LY379268 tested reduced spontaneous locomotor activity and operant responding maintained by a non-drug reinforcer, without differences among groups. The heightened sensitivity to the effects of LY379268 in rats with an ethanol-dependence history was therefore specific to behavior motivated by ethanol-related stimuli. Both the SW and RW groups showed elevated [35S]GTPγS binding in the central nucleus of the amygdala (CeA) and bed nucleus of stria terminalis (BNST), relative to the CTRL group. The findings implicate changes in mGluR2/3 functional activity as a factor in ethanol dependence and support treatment target potential of mGlu2/3 receptors for craving and relapse prevention. PMID:21881571

Effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline on glutamate transporter 1 and cysteine/glutamate exchanger as well as ethanol drinking behavior in male, alcohol-preferring rats.

PubMed

Aal-Aaboda, Munaf; Alhaddad, Hasan; Osowik, Francis; Nauli, Surya M; Sari, Youssef

2015-06-01

Alcohol consumption is largely associated with alterations in the extracellular glutamate concentrations in several brain reward regions. We recently showed that glutamate transporter 1 (GLT-1) is downregulated following chronic exposure to ethanol for 5 weeks in alcohol-preferring (P) rats and that upregulation of the GLT-1 levels in nucleus accumbens and prefrontal cortex results, in part, in attenuating ethanol consumption. Cystine glutamate antiporter (xCT) is also downregulated after chronic ethanol exposure in P rats, and its upregulation could be valuable in attenuating ethanol drinking. This study examines the effect of a synthetic compound, (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), on ethanol drinking and expressions of GLT-1 and xCT in the amygdala and the hippocampus of P rats. P rats were exposed to continuous free-choice access to water, 15% and 30% ethanol, and food for 5 weeks, after which they received treatments of MS-153 or vehicle for 5 days. The results show that MS-153 treatment significantly reduces ethanol consumption. It was revealed that GLT-1 and xCT expressions were downregulated in both the amygdala and the hippocampus of ethanol-vehicle-treated rats (ethanol-vehicle group) compared with water-control animals. MS-153 treatment upregulated GLT-1 and xCT expressions in these brain regions. These findings demonstrate an important role for MS-153 in these glutamate transporters for the attenuation of ethanol-drinking behavior. © 2015 Wiley Periodicals, Inc.

Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

PubMed

Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

2011-06-01

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared with group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition, experience with CVS early in life results in elevated ethanol intake later in adulthood. Taken together, these results emphasize the important role of early stress experiences that modulate later voluntary ethanol intake during adulthood. Copyright © 2011 Elsevier Inc. All rights reserved.

Calcium hydroxide associated with a new vehicle: Psidium cattleianum leaf extracts. Tissue response evaluation.

PubMed

Valentim, Diego; Bueno, Carlos Roberto Emerenciano; Marques, Vanessa Abreu Sanches; Vasques, Ana Maria Veiga; Cury, Marina Tolomei Sandoval; Cintra, Luciano Tavares Angelo; Dezan, Eloi

2017-07-03

The aim of this study was to evaluate edemogenic activity and subcutaneous inflammatory reaction induced by Psidium cattleianum leaf extracts associated with Ca(OH)2. Thirty male Wistar rats, split equally into three groups [aqueous extract + Ca(OH)2; ethanolic extract + Ca(OH)2; and propylene glycol + Ca(OH)2], were assessed every 3 h or 6 h (five animals in each period). Under general anesthesia, 0.2 mL of 1% Evans blue per 100 g of body weight was injected into the penile vein and each combination to be evaluated was subcutaneously injected into the dorsal region 30 min thereafter. Edemogenic activity was analyzed by spectrophotometry (λ=630 nm). For inflammatory reaction analysis, 50 rats received four polyethylene tubes (three experimental groups) and an empty tube (control group). The assessments were made at 7, 15, 30, 60, and 90 days, followed by hematoxylin-eosin staining and by the assignment of scores for evaluation of tissue response intensity. Ethanolic extract + Ca(OH)2 yielded the largest edemogenic activity at 3 h. Intergroup differences at 6 h were not significant. The histological analysis showed progressive repair over time (p<0.05) and aqueous and ethanolic extracts produced similar responses to those of the control and Ca(OH)2 + propylene glycol groups. Psidium cattleianum leaf extracts used as Ca(OH)2 vehicles evoked similar tissue response when compared to Ca(OH)2 associated with propylene glycol.

Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats.

PubMed

Kim, Gyeong-Ji; Song, Da Hye; Yoo, Han Seok; Chung, Kang-Hyun; Lee, Kwon Jai; An, Jeung Hee

2017-01-06

In this study, we determined the effects of hederagenin isolated from Akebia quinata fruit on alcohol-induced hepatotoxicity in rats. Specifically, we investigated the hepatoprotective, anti-inflammatory, and anti-apoptotic effects of hederagenin, as well as the role of AKT and mitogen-activated protein kinase (MAPK) signaling pathways in ethanol-induced liver injury. Experimental animals were randomly divided into three groups: normal (sham), 25% ethanol, and 25% ethanol + hederagenin (50 mg/kg/day). Each group was orally administered the respective treatments once per day for 21 days. Acetaldehyde dehydrogenase-2 mRNA expression was higher and alcohol dehydrogenase mRNA expression was lower in the ethanol + hederagenin group than those in the ethanol group. Pro-inflammatory cytokines, including TNF-α, IL-6, and cyclooxygenase-2, significantly increased in the ethanol group, but these increases were attenuated by hederagenin. Moreover, Western blot analysis showed increased expression of the apoptosis-associated protein, Bcl-2, and decreased expression of Bax and p53 after treatment with hederagenin. Hederagenin treatment attenuated ethanol-induced increases in activated p38 MAPK and increased the levels of phosphorylated AKT and ERK. Hederagenin alleviated ethanol-induced liver damage through anti-inflammatory and anti-apoptotic activities. These results suggest that hederagenin is a potential candidate for preventing alcoholic liver injury.

Therapeutic effect of low molecular weight chitosan containing sepia ink on ethanol-induced gastric ulcer in rats.

PubMed

Zhang, Wei; Liu, Kang; Li, Lei; Li, Yingxin; Sui, Xianxian; Rao, Yinzhu; Wu, Jiahao; Wu, Qiuping

2016-12-01

To evaluate the role of low molecular chitosan containing sepia ink (LMCS) in ethanol-induced (5 ml/kg) gastric ulcer in rats. Animals were divided into four groups (n = 12): normal group (Normal), negative control group (Con), experiment group (LMCS) and positive control Omeprazole group (OMZ). Gastric empty rate was detected in the first 7 days. Rats were sacrificed at 7, 14 and 21 day for histology and ELISA detections. Gastric empty was no significant differences among the groups (P > 0.05). Histological observation showed gastric mucosal LMCS treated had better healing effect. Hydroxyproline (Hyp) was significantly increased from 7 day (P < 0.05). LMCS significantly inhibited malondialdehyde (MDA) generation for lipid peroxidation from 7 day (P < 0.05). LMCS significantly promoted the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) at the earlier stage (P < 0.05). OMZ had the similar effects above. As for myeloperoxidase (MPO), LMCS significantly decreased and restored it to normal levels from 7 day (P < 0.05), it is earlier than OMZ which is from 14 day. LMCS can improve gastric mucosa tissue repair, exert significant influences on oxidative and antioxidant enzyme activities and neutrophil infiltration.

Observation of Trans-Ethanol and Gauche-Ethanol Complexes with Benzene Using Matrix Isolation Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Amicangelo, Jay; Silbaugh, Matthew J.

2016-06-01

Ethanol can exist in two conformers, one in which the OH group is trans to the methyl group (trans-ethanol) and the other in which the OH group is gauche to the methyl group (gauche-ethanol). Matrix isolation infrared spectra of ethanol deposited in 20 K argon matrices display distinct infrared peaks that can be assigned to the trans-ethanol and gauche-ethanol conformers, particularly with the O-H stretching vibrations. Given this, matrix isolation experiments were performed in which ethanol (C_2H_5OH) and benzene (C_6H_6) were co-deposited in argon matrices at 20 K in order to determine if conformer specific ethanol complexes with benzene could be observed in the infrared spectra. New infrared peaks that can be attributed to the trans-ethanol and gauche-ethanol complexes with benzene have been observed near the O-H stretching vibrations of ethanol. The initial identification of the new infrared peaks as being due to the ethanol-benzene complexes was established by performing a concentration study (1:200 to 1:1600 S/M ratios), by comparing the co-deposition spectra with the spectra of the individual monomers, by matrix annealing experiments (35 K), and by performing experiments using isotopically labeled ethanol (C_2D_5OD) and benzene (C_6D_6). Quantum chemical calculations were also performed for the C_2H_5OH-C_6H_6 complexes using density functional theory (B3LYP) and ab initio (MP2) methods. Stable minima were found for the both the trans-ethanol and gauche-ethanol complexes with benzene at both levels of theory and were predicted to have similar interaction energies. Both complexes can be characterized as H-π complexes, in which the ethanol is above the benzene ring with the hydroxyl hydrogen interacting with the π cloud of the ring. The theoretical O-H stretching frequencies for the complexes were predicted to be shifted from the monomer frequencies and from each other and these results were used to make the conformer specific infrared peak assignments. Barnes, A. J.; Hallam, H. E. Trans. Faraday Soc., 1970, 66, 1932-1940.

Detection heart failures (HF) biomarkers by proton transfer reaction - mass spectrometry and ion mobility spectrometry

NASA Astrophysics Data System (ADS)

Shaltaeva, Y. R.; Vasilev, V. K.; Yakovlev, D. Y.; Kopylov, F. Iu; Syrkin, A. L.; Chomakhidze, P. Sh; Bykova, A. A.; Malinovskaya, L. K.; Skorokhod, A. I.

2016-10-01

Exhaled breath contains 1% of volatile organic compounds. The concentration of individual biomarkers in hundreds of volatile organic compounds lies within the range ppm- ppb. In compare with control group the concentrations of acetone, acetic acid, ethanol, propylene biomarkers is significantly higher in HF-PEF group.

Alcohol preference drinking in a mouse line selectively bred for high drinking in the dark.

PubMed

Crabbe, John C; Spence, Stephanie E; Brown, Lauren L; Metten, Pamela

2011-08-01

We have selectively bred mice that reach very high blood ethanol concentrations (BECs) after drinking from a single bottle of 20% ethanol. High Drinking in the Dark (HDID-1) mice drink nearly 6g/kg ethanol in 4h and reach average BECs of more than 1.0mg/mL. Previous studies suggest that DID and two-bottle preference for 10% ethanol with continuous access are influenced by many of the same genes. We therefore asked whether HDID-1 mice would differ from the HS/Npt control stock on two-bottle preference drinking. We serially offered mice access to 3-40% ethanol in tap water versus tap water. For ethanol concentrations between 3 and 20%, HDID-1 and HS/Npt controls did not differ in two-bottle preference drinking. At the highest concentrations, the HS/Npt mice drank more than the HDID-1 mice. We also tested the same mice for preference for two concentrations each of quinine, sucrose, and saccharin. Curiously, the mice showed preference ratios (volume of tastant/total fluid drunk) of about 50% for all tastants and concentrations. Thus, neither genotype showed either preference or avoidance for any tastant after high ethanol concentrations. Therefore, we compared naive groups of HDID-1 and HS/Npt mice for tastant preference. Results from this test showed that ethanol-naive mice preferred sweet fluids and avoided quinine but the genotypes did not differ. Finally, we tested HDID-1 and HS mice for an extended period for preference for 15% ethanol versus water during a 2-h access period in the dark. After several weeks, HDID-1 mice consumed significantly more than HS. We conclude that drinking in the dark shows some genetic overlap with other tests of preference drinking, but that the degree of genetic commonality depends on the model used. Published by Elsevier Inc.

Lever conditioned stimulus-directed autoshaping induced by saccharin-ethanol unconditioned stimulus solution: effects of ethanol concentration and trial spacing.

PubMed

Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A

2003-05-01

Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance of Pavlovian-autoshaping CRs.

Dose- and time-dependent effects of ethanolic extract of Mucuna pruriens Linn. seed on sexual behaviour of normal male rats.

PubMed

Suresh, Sekar; Prithiviraj, Elumalai; Prakash, Seppan

2009-04-21

According to Indian Systems of Medicine, Mucuna pruriens Linn., belonging to the leguminous family (Papilionaceae), were used for treating male sexual disorders since ancient times. In this study, the effects of ethanolic extracts of the Mucuna pruriens Linn. seed on general mating behaviour, libido and potency of normal male Wister albino rats were investigated and also compared with the standard reference drug, Sildenafil citrate. Animals were divided into one control group (Group I--received saline) and four experimental groups (Groups II-V). Experimental groups were divided on the basis of the dosage of extract to the animals as follows: 150 mg/kg body weight (Group I), 200mg/kg body weight (Group II) and 250 mg/kg body weight (Group IV) while Group V received Sildenafil citrate (5mg/kg body weight). Animals were fed PO with saline or extract or standard drug once in a day for 45 days. To analyse the mating behaviour, female rats with oestrus phase were used. The extract administered PO significantly increased the mounting frequency, intromission frequency and ejaculation latency, and decreased the mounting latency, intromission latency, post-ejaculatory interval and inter-intromission interval. The potency test significantly increased erections, quick flips, long flips and total reflex. Therefore, the results indicated that the ethanolic extracts of Mucuna pruriens Linn. seed produced a significant and sustained increase in the sexual activity of normal male rats at a particular dose (200mg/kg). When compared to control, all the drug-treated groups have shown drug-induced effects for a few parameters. However in Group II, there was an obvious enhancement in all parameters, without affecting the normal behaviour. When compared with the standard drug, the net effect of extract is even less than that in Group II. Therefore, the resulting aphrodisiac activity of the extract lends support to the claim that it has traditionally been used for the treatment of sexual disorders.

Neurolaena lobata L. promotes wound healing in Sprague Dawley rats.

PubMed

Nayak, Bijoor Shivananda; Ramlogan, Surrin; Chalapathi Rao, Av; Maharaj, Sandeep

2014-07-01

The leaves of the Neurolaena lobata (Asteraceae) plant are used to control diabetes and heal wounds and infections. The ethanolic extract of N. lobata leaf was evaluated for its ability to heal inflicted wounds in rats using the excision wound model. Animals were divided into three groups of six each. Test group animals were treated topically with an ethanolic extract of N. lobata (1:1 with petroleum jelly, 100 mg/kg/day). Standard and control group animals were treated with mupirocin and petroleum jelly, respectively. Treatment was given for 13 days and the wound area was measured on alternate days. Parameters of healing assessed were the rate of wound contraction, period of epithelialization and hydroxyproline content. Antimicrobial activity of the extract was observed against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Phytochemical analysis of the extract showed the presence of saponins, tannins, alkaloids and flavanoids. Extract-treated animals exhibited 87% reduction in the wound area over 13 days when compared with the control (78%) and standard (83%) groups (P < 0.05). A significant decrease in the epithelialization period was noticed with the extract-treated test group animals compared with the controls and the standard group animals (P < 0.008). The hydroxyproline content of the extract-treated animals was higher (230.5 ± 42.1) when evaluated against the control and (79.0 ± 32.2) and the standard (115.0 ± 44.5) groups (P < 0.05). Increase in the rate of wound contraction and hydroxyproline content with decrease in epithelialization time in extract-treated animals support further evaluation of N. lobata as a pharmacotherapy for wound healing.

Nucleus accumbens lentiviral-mediated gain of function of the oxytocin receptor regulates anxiety- and ethanol-related behaviors in adult mice.

PubMed

Bahi, Amine; Al Mansouri, Shamma; Al Maamari, Elyazia

2016-10-01

Anxiety is believed to influence ethanol use human in alcoholics. Studies using laboratory animals suggested an interaction between oxytocin and the behavioral effects of ethanol. Our previous study implicated a potential role for the oxytocin receptor (OxtR) in regulating ethanol-conditioned place preference. Here, we examined anxiety and the behavioral responses to ethanol in C57BL/6 mice stereotaxically injected in the nucleus accumbens (NAcc) with lentiviral vectors expressing an empty vector (Mock) or the OxtR cDNA. For anxiety we used the elevated-plus maze, the open-field and the marble-burying tests and for ethanol we used the two-bottle choice paradigm, the wire-hanging and ethanol-induced loss-of-righting-reflex tests. We found that, compared to Mock, OxtR overexpression led to anxiolytic-like behavior without altering spontaneous locomotor activity. Most importantly, we found that, relative to Mock controls, increased expression of the OxtR in the NAcc led to decreased ethanol consumption and preference in the two-bottle choice protocol and increased resistance to ethanol-induced sedation. We also compared the consequence of OxtR modulation on the consumption and preference of saccharin and quinine and found that the two experimental groups did not differ for any tastant. These results provide further evidence that the oxytocin system contributes to the regulation of ethanol drinking and sensitivity and position OxtR as a central molecular mediator of ethanol's effects within the mesolimbic system. Taken together, the current findings suggest that OxtR manipulation may be a relevant strategy to address ethanol use disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt.

PubMed

Ibrahim, N A; Shalaby, A S; Farag, R S; Elbaroty, G S; Nofal, S M; Hassan, E M

2008-04-15

Flavonoid glycosides, orientin and apigenin 3, 8-di-C-glycosides in addition to, iridoid compound, aucubin were isolated from the ethanolic extract of Vitex agnus-castus fruits. Their structures were identified on the basis of the spectroscopic data. The estrogenic activity of the ethanolic extract in two dose levels 0.6 and 1.2 g kg(-1) per body weight (b.w.) was studied by the vaginal smear, and uterine weight methods for normal and ovariectomized female rats. The extract induced significant increase in the uterine weight of ovariectomized rats at two dose levels comparable to that of control group. The percentages of the total average number of scores were increased significantly too. Significant increases in plasma progesterone and total estrogens levels were shown at the two dose levels when compared to that of control group. On the other side, the extract induced significant reduction in luteinizing and plasma prolactin hormones.

Comparative study of teratogenic potentials of crude ethanolic root bark and leaf extract of Rauwolfia vomitoria (apocynaceae) on the fetal heart

PubMed Central

Eluwa, Mokutima A.; Udoaffah, Matilda T.; Vulley, Moses B. G.; Ekanem, Theresa B.; Akpantah, Amabe O.; Asuquo, Olaitan A.; Ekong, Moses B.

2010-01-01

Background: Rauwolfia vomitoria, a tropical shrub, is a medicinal plant used in the treatment of a variety of ailments. It is popular to the locals because of its anti-hypertensive and sedative properties. Aim: This is to find the probable teratogenic effects of ethanolic leaf and root bark extracts of Rauwolfia vomitoria on the morphological and histological features of the fetal heart. Material and Methods: Twenty five female rats weighing between 170-200g were used for this study. The rats were divided into five groups labeled A, B, C, D and E, with each group consisting of five rats. Pregnancy was induced by caging the female rats with sexually matured males. The presence of vaginal plug and tail structures in the vaginal smear the following morning confirmed coition, and it was regarded as day 0 of pregnancy. Group A was given sham treatment of distilled water. Group B and C received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic leaf extract of Rauwolfia vomitoria, and those in groups D and E received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic root bark extract of Rauwolfia vomitoria. These treatments were on days 7-11 of gestation (5 days) with the aid of an orogastric tube. On the day 20 of gestation, the rats were sacrificed and the fetuses examined for gross anomalies, preserved and latter process for histological studies. Results: There were no mortality in this study, and no obvious gross malformations in the fetuses. Histological observations of the fetal heart showed marked distortion of the cardiac muscle nuclei and myocardial fibers in the treated groups particularly those whose mothers received 250mg/kg of the extracts. These effects were more pronounced in the groups whose mothers received the root extract when compared with the control and the groups whose mothers received the leaf extract. Conclusion: This result suggests that high doses of ethanolic leaf and root extracts of Rauwolfia vomitoria may be cardiotoxic to the developing rat's heart. PMID:22558573

Comparative study of teratogenic potentials of crude ethanolic root bark and leaf extract of Rauwolfia vomitoria (apocynaceae) on the fetal heart.

PubMed

Eluwa, Mokutima A; Udoaffah, Matilda T; Vulley, Moses B G; Ekanem, Theresa B; Akpantah, Amabe O; Asuquo, Olaitan A; Ekong, Moses B

2010-12-01

Rauwolfia vomitoria, a tropical shrub, is a medicinal plant used in the treatment of a variety of ailments. It is popular to the locals because of its anti-hypertensive and sedative properties. This is to find the probable teratogenic effects of ethanolic leaf and root bark extracts of Rauwolfia vomitoria on the morphological and histological features of the fetal heart. Twenty five female rats weighing between 170-200g were used for this study. The rats were divided into five groups labeled A, B, C, D and E, with each group consisting of five rats. Pregnancy was induced by caging the female rats with sexually matured males. The presence of vaginal plug and tail structures in the vaginal smear the following morning confirmed coition, and it was regarded as day 0 of pregnancy. Group A was given sham treatment of distilled water. Group B and C received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic leaf extract of Rauwolfia vomitoria, and those in groups D and E received respectively 150mg/kg and 250mg/kg body weight doses of ethanolic root bark extract of Rauwolfia vomitoria. These treatments were on days 7-11 of gestation (5 days) with the aid of an orogastric tube. On the day 20 of gestation, the rats were sacrificed and the fetuses examined for gross anomalies, preserved and latter process for histological studies. There were no mortality in this study, and no obvious gross malformations in the fetuses. Histological observations of the fetal heart showed marked distortion of the cardiac muscle nuclei and myocardial fibers in the treated groups particularly those whose mothers received 250mg/kg of the extracts. These effects were more pronounced in the groups whose mothers received the root extract when compared with the control and the groups whose mothers received the leaf extract. This result suggests that high doses of ethanolic leaf and root extracts of Rauwolfia vomitoria may be cardiotoxic to the developing rat's heart.

Protective effect of δ-amyrone against ethanol-induced gastric ulcer in mice.

PubMed

Li, Weifeng; Yao, Huan; Niu, Xiaofeng; Wang, Yu; Zhang, Hailin; Li, Huani; Mu, Qingli

2015-06-01

The purpose of this study is to examine the protective effect of δ-amyrone on ethanol-induced gastric ulcer in mice. The mice intragastric administration 75% (0.5 mL/100g) ethanol was pretreated with δ-amyrone (4 and 8 mg/kg) and cimetidine (100 mg/kg) or vehicles in different experimental groups for a continuous three-day, and animals were euthanized 3h after ethanol ingestion. The gastric lesions were significantly attenuated by δ-amyrone (4 and 8 mg/kg) as compared to the ulcer control group. Pre-treatment with δ-amyrone prevented the myeloperoxidase (MPO) activity, production of nitric oxide (NO) in serum, expression of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) p65 protein expression. Analysis of cytokines in gastric tissue and serum of ethanol-induced mice showed the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased by δ-amyrone in response to NF-κB p65. These results suggested that δ-amyrone exerts its protective effect on experimental gastric ulcer by inhibiting NF-κB signaling pathways, which subsequently reduces overproduction of the inducible enzymes iNOS and suppresses the release of the inflammatory factors TNF-α, IL-6 and NO. Thus, δ-amyrone shows promise as a therapeutic agent in experimental gastric ulcer. Copyright © 2014 Elsevier GmbH. All rights reserved.

Gastroprotective effects of the essential oil of Hyptis crenata Pohl ex Benth. on gastric ulcer models.

PubMed

Diniz, Lúcio Ricardo Leite; Vieira, Charliene Freire Xavier; Santos, Edgleyson Chaves Dos; Lima, Glauber Cruz; Aragão, Kalynca Kayla Viana; Vasconcelos, Renata Prado; Araújo, Pâmella Cristina da Costa; Vasconcelos, Yuri de Abreu Gomes; Oliveira, Ariclécio Cunha de; Oliveira, Hermógenes David de; Portella, Viviane Gomes; Coelho-de-Souza, Andrelina Noronha

2013-10-07

Hyptis crenata Pohl ex Benth (Lamiaceae), popularly known as "hortelã-brava" or "hortelã do campo", is widely distributed in the northeast of Brazil. In Brazil, the leaves of this plant have been used in traditional medicine for the treatment of gastrointestinal disturbances, including gastric ulcers. In an attempt to experimentally validate this claimed antiulcerogenic activity, the gastroprotective effects of the essential oil extracted from the leaves of the Hyptis crenata Pohl ex Benth (EOHc) were evaluated in recognized gastric ulcer models in mice. EOHc was obtained by hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC-MS). Swiss male mice (25-30g) were used for the studies. The gastric ulcers were induced by oral administration of absolute ethanol or indomethacin 45min after oral pretreatment with EOHc, vehicle and positive control drugs. One hour after the ulcerative challenges, the stomachs were removed and the area of the lesions was measured. The volume, pH and total acidity of the gastric secretions were determined using the pylorus ligature model. The gastrointestinal motility was measured using gastric emptying and intestinal transit. The ethanol-induced gastric mucus depletion and lipid peroxidation were also analyzed. Our findings are as follows: A significant inhibition of gastric lesions induced by absolute ethanol was observed in the mice pre-treated with EOHc, at a dose of 30 and 100 and 300mg/kg (5.56±1.51, 2.88±0.82 and 1.71±0.54mm(2), respectively) compared to control group (118.03±35.4mm(2)). Also, EOHc (300mg/kg) produced a gastroprotective effect against the gastric lesions induced by indomethacin (16.07±4.68mm(2)) compared to control group (38.64±6.1mm(2)). EOHc pretreatment produced a reduction in the ethanol-induced lipid peroxidation from 3.9±0.22 to 2.4±0.1μmol/mg tissue (EOHc-300mg/kg and control group, respectively). We also observed that EOHc pretreatment decreased the gastric emptying, but did not alter the intestinal transit ratio, ethanol-induced depletion of the gastric wall mucus or secretion parameters (volume, pH and [H(+)]). Our data indicate that EOHc exerts a gastroprotective effect, indicated by its significant inhibition of gastric lesions in ethanol- and indomethacin-induced ulcer models, which may be associated with its accelerating effect on gastric emptying and reduction in oxidative damages. Our data suggest a potential therapeutic application for EOHc in the treatment of gastric ulcers. © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects of acute administration of ethanol on the rat adrenal cortex.

PubMed

Milovanović, Tatjana; Budec, Mirela; Balint-Perić, Ljiljana; Koko, Vesna; Todorović, Vera

2003-09-01

The purpose of this study was to investigate the effect of a single dose of ethanol on rat adrenal cortex and to determine whether the estrous cycle can influence this effect of ethanol. Adult female Wistar rats showing proestrus or diestrus Day 1 (n = 12) were treated intraperitoneally with ethanol (4 g/kg body weight). Untreated (n = 15) and saline-injected (n = 14) rats were used as controls. The animals were sacrificed by decapitation 0.5 hour after ethanol administration. Stereological analysis was performed on paraffin sections of adrenal glands stained with AZAN, and the following parameters were determined: absolute volume of the zona glomerulosa, the zona fasciculata and the zona reticularis, numerical density, volume and the mean diameter of adrenocortical cells and of their nuclei, and diameter and length of capillaries. The diameter and volume of adrenocortical cells in the zona fasciculata and the zona reticularis were significantly increased by acute ethanol treatment at proestrus. In the same group of animals, a single dose of ethanol induced significant decrease in numerical density of adrenocortical cells and of their nuclei in all three zones. Increased length of capillaries of the zona fasciculata as well as enhanced level of serum corticosterone was found in ethanol-treated rats at both phases of the estrous cycle, proestrus and diestrus Day 1. The obtained results indicate that a single dose of ethanol activates adrenal cortex in female rats and that the effect is more pronounced on morphometric parameters at proestrus.

In vitro vitamin K3 effect on conjunctival fibroblast migration and proliferation.

PubMed

Pinilla, I; Izaguirre, L B; Gonzalvo, F J; Piazuelo, E; Garcia-Gonzalez, M A; Sanchez-Cano, A I; Sopeña, F

2014-01-01

To evaluate the dose effect of vitamin K3 on wound healing mechanisms. Conjunctival fibroblasts were incubated for 24 hours. An artificial wound was made and the cells were incubated with fresh medium plus doses of vitamin K3 to be tested. Wound repair was monitored at 0, 18, 24, and 48 hours. Proliferation was measured in actively dividing cells by [(3)H]thymidine uptake. Six different groups were tested: group 1/no drugs added, group 2/ethanol 0.1%, group 3/vitamin K3 1 mg/L, group 4/vitamin K3 2 mg/L, group 5/vitamin K3 4 mg/L, and group 6/vitamin K3 6 mg/L. Each experiment was carried out in triplicate and 4 times. There were no differences among groups at the initial time. In vitro wound repair was slower in groups 4, 5, and 6. There were no differences between control and ethanol groups and between control and vitamin K3 1 mg/L groups. Fibroblast mitogenic activity was statistically decreased in all vitamin K groups; statistical differences were found among vitamin K3 1 mg/mL and higher doses too. In groups 5 and 6, cellular toxicity was presented. Vitamin K3 is able to inhibit fibroblast proliferation. Vitamin K3 2 mg/L or higher doses inhibit wound healing repair, exhibiting cellular toxicity at 4 and 6 mg/L.

Randomized Controlled Ethanol Cookstove Intervention and Blood Pressure in Pregnant Nigerian Women.

PubMed

Alexander, Donee; Northcross, Amanda; Wilson, Nathaniel; Dutta, Anindita; Pandya, Rishi; Ibigbami, Tope; Adu, Damilola; Olamijulo, John; Morhason-Bello, Oludare; Karrison, Theodore; Ojengbede, Oladosu; Olopade, Christopher O

2017-06-15

Hypertension during pregnancy is a leading cause of maternal mortality. Exposure to household air pollution elevates blood pressure (BP). To investigate the ability of a clean cookstove intervention to lower BP during pregnancy. We conducted a randomized controlled trial in Nigeria. Pregnant women cooking with kerosene or firewood were randomly assigned to an ethanol arm (n = 162) or a control arm (n = 162). BP measurements were taken during six antenatal visits. In the primary analysis, we compared ethanol users with control subjects. In subgroup analyses, we compared baseline kerosene users assigned to the intervention with kerosene control subjects and compared baseline firewood users assigned to ethanol with firewood control subjects. The change in diastolic blood pressure (DBP) over time was significantly different between ethanol users and control subjects (P = 0.040); systolic blood pressure (SBP) did not differ (P = 0.86). In subgroup analyses, there was no significant intervention effect for SBP; a significant difference for DBP (P = 0.031) existed among preintervention kerosene users. At the last visit, mean DBP was 2.8 mm Hg higher in control subjects than in ethanol users (3.6 mm Hg greater in control subjects than in ethanol users among preintervention kerosene users), and 6.4% of control subjects were hypertensive (SBP ≥140 and/or DBP ≥90 mm Hg) versus 1.9% of ethanol users (P = 0.051). Among preintervention kerosene users, 8.8% of control subjects were hypertensive compared with 1.8% of ethanol users (P = 0.029). To our knowledge, this is the first cookstove randomized controlled trial examining prenatal BP. Ethanol cookstoves have potential to reduce DBP and hypertension during pregnancy. Accordingly, clean cooking fuels may reduce adverse health impacts associated with household air pollution. Clinical trial registered with www.clinicaltrials.gov (NCT02394574).

Light-to-moderate ethanol feeding augments AMPK-α phosphorylation and attenuates SREBP-1 expression in the liver of rats.

PubMed

Nammi, Srinivas; Roufogalis, Basil D

2013-01-01

Fatty liver disease, a hepatic manifestation of metabolic syndrome, is one of the major causes of chronic liver diseases. Epidemiological studies suggest that regular light-to-moderate ethanol consumption lowers the risk of developing metabolic disorders including dislipidemia, insulin resistance, type 2 diabetes and fatty liver disease. However, the mechanism(s) of the protective effect of light-to-moderate ethanol consumption on the liver remains unknown. In the present study, we investigated the effects of light (6%, 0.94 g/kg/day) and moderate (12%, 1.88 g/kg/day) ethanol feeding in rats for 3 weeks on the circulating and hepatic biochemical profiles and on the hepatic protein expression and phosphorylation status of adenosine monophosphate-activated protein kinase-α (AMPK-α) and other down-stream targets of this enzyme including sterol regulatory element-binding protein-1 (SREBP-1), SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase). Despite no significant difference in food-intake among the groups, light ethanol treatment significantly increased the body weight compared to control rats. Serum glucose, insulin, total cholesterol, triglycerides, phospholipids and hepatic cholesterol and triglycerides were not significantly different among the groups. However, serum free fatty acids were significantly reduced with light ethanol treatment. Both light and moderate ethanol treatment significantly increased the hepatic levels of phosphorylated AMPK-α protein and this was associated with significant reduction of SREBP-1 protein expression, suggesting an enhanced fatty acid oxidation. In addition, light ethanol treatment significantly decreased the SCAP protein expression in the liver. However, liver HMG-CoA protein expression was not significantly different with ethanol consumption. Chronic light-to-moderate ethanol consumption increased AMPK activation which was associated with decreased expression of SREBP-1 and SCAP in the liver. Thus, our studies provide mechanistic evidence for the earlier epidemiological studies that indicate light-to-moderate ethanol intake lowers the risk of development of fatty liver disease and other metabolic disorders. Our studies demonstrate that the protective effects of light-to-moderate ethanol arise at least in part by increased phosphorylation of AMPK-α and decreased SREBP-1 expression in the liver. Further studies are warranted to determine the effects of light-to-moderate ethanol on intracellular up-stream and down-stream targets of AMPK and also on the implications of light-to-moderate ethanol in protecting non-alcoholic fatty liver disease.

Ethanol extract of the leaves of Psidium guajava Linn enhances sperm output in healthy Wistar rats.

PubMed

Akinola, O B; Oladosu, O S; Dosumu, O O

2007-06-01

Reactive oxygen species (ROS), among other factors, have been implicated in the aetiology of male infertility. Thus, the roles of antioxidants at improving sperm production and quality are being investigated. The present study was designed to assess the effect of the ethanol extract of fresh leaves of Psidium guajava Linn. on the sperm parameters of healthy male Wistar rats. A total of 18 rats, weighing between 108-124 g, were divided into 3 groups of 6 animals each. Animals in groups 1 and 2 were administered 250 mg/kg/d and 500 mg/kg/d of guava leaf extract (GLE) orally for 53 days respectively. Group 3 animals received normal saline. Sperm count increased from 56.2+/-0.3 (x10(6)) in the control to 57.1+/-0.2 (x10(6)) in group 1 animals, and from 56.2+/-0.3 (x10(6)) in the control to 72.3+/-0.4 (x10(6)) in group 2 animals. Similarly, dose-dependent increases in the percentages of motile spermatozoa were observed in GLE-treated animals compared to the control group. These findings suggest that the extracts of the leaves of Psidium guajava Linn. possess beneficial effects on sperm production and quality, and may thus improve the sperm parameters of infertile males with oligospermia and nonobstructive azoospermia.

Comparison of antibacterial activity of Talok (Muntingia calabura L) leaves ethanolic and n-hexane extracts on Propionibacterium acnes

NASA Astrophysics Data System (ADS)

Desrini, Sufi; Ghiffary, Hifzhan Maulana

2018-04-01

Muntingia calabura L., also known locally as Talok or Kersen, is a plant which has been widely used as traditional medicine in Indonesia. In this study, we evaluated the antibacterial activity of Muntingia calabura L. Leaves ethanolic and n-hexane extract extract on Propionibacterium acnes. Antibacterial activity was determined in the extracts using agar well diffusion method. The antibacterial activities of each extract (2 mg/mL, 8 mg/ml, 20 mg/mL 30 mg/mL, and 40 mg/mL) were tested against to Propionibacterium acnes. Zone of inhibition of ethanolic extract and n-hexane extract was measured, compared, and analyzed by using a statistical programme. The phytochemical analyses of the plants were carried out using thin chromatography layer (TLC). The average diameter zone of inhibition at the concentration of 2 mg/mL of the ethanolic extract is 9,97 mm while n-Hexane extract at the same concentration showed 0 mm. Statistical test used was non-parametric test using Kruskal Wallis test which was continued to the Mann-Whitney to see the magnitude of the difference between concentration among groups. Kruskal-Wallis test revealed a significant value 0,000. Based on the result of Post Hoc test using Mann - Whitney test, there is the statistically significant difference between each concentration of ethanolic extract and n-hexane as well as positive control group (p-value < 0,05). Both extracts have antibacterial activity on P.acne. However, ethanolic extract of Muntingia calabura L. is better in inhibiting Propionibacterium acnes growth than n-hexane extract.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

PubMed

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, comparedmore » to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic ethanol feeding causes oxidative stress, ER stress and inflammation in lungs of ADH– deer mice. • Chronic ethanol feeding generates FAEEs (nonoxidative metabolites of ethanol) in lungs of ADH– deer mice. • Chronic ethanol feeding induces CYP2E1 in the lungs of ADH– deer mice. • Lack of ER homeostasis due to a prolonged ethanol feeding could trigger inflammation.« less

Protective role of extracts of grape skin and grape flesh on ethanol-induced oxidative stress, inflammation and histological alterations in rat brain.

PubMed

Mukherjee, Sukhes; Das, Subir Kumar; Vasudevan, D M

2015-01-01

Ethanol consumption has deleterious effects on all organs and especially on brain. In our study, the radical scavenging properties of grape skin and grape flesh (contains natural antioxidants like polyphenols) was determined in vitro and for in vivo studies, male Wistar rats (16-18 week-old) and 100-120 gm weight were divided in five groups of six animals each. One group were fed with ethanol (1.6 gm/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and grape skin extract (2.5 g/kg body weight), the third group were fed with ethanol (1.6 g/kg body weight) and grape flesh extract, daily once for 12 weeks, while the fourth group were fed with ethanol (1.6 g/kg body weight) and tocopheryl acetate (80 mg/kg/day) daily once for 12 weeks. Results of in vitro studies indicate that grape skin extracts showed significant radical scavenging properties (ROS). There was also significantly alteration of serum cytokines in our study.

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding.

PubMed

Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S; Calhoun, William J

2014-06-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to <1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

PubMed Central

Kaphalia, Lata; Boroumand, Nahal; Ju, Hyunsu; Kaphalia, Bhupendra S.; Calhoun, William J.

2014-01-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to <0.2% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 were observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. PMID:24625836

Tolerance to disulfiram induced by chronic alcohol intake in the rat.

PubMed

Tampier, Lutske; Quintanilla, María Elena; Israel, Yedy

2008-06-01

Disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism, is an effective medication when its intake is supervised by a third person. However, its therapeutic efficacy varies widely, in part due to the fact that disulfiram is a pro-drug that requires its transformation into an active form and because it shows a wide range of secondary effects which often prevent the use of doses that ensure full therapeutic effectiveness. In this preclinical study in rats we report the development of tolerance to disulfiram induced by the chronic ingestion of ethanol, an additional source of variation for the actions of disulfiram with possible therapeutic significance, We also addresses the likely mechanism of this effect. Wistar-derived rats bred for generations as high ethanol drinkers (UChB) were trained for either 3 days (Group A) or 30 days (Group B) to choose between ethanol (10% v/v) or water, which were freely available from 2 bottles on a 24-hour basis. Subsequently, animals in both groups were administered disulfiram or cyanamide (another inhibitor of aldehyde dehydrogenase) and ethanol intake in this free choice paradigm was determined. Animals were also administered a standard dose of 1 g ethanol/kg (i.p) and arterial blood acetaldehyde was measured. Disulfiram (12.5 and 25 mg/kg) and cyanamide (10 mg/kg) markedly inhibited ethanol intake (up to 60 to 70%) in animals that had ethanol access for only 3 days (Group A). However both drugs were inactive in inhibiting ethanol intake in animals that had consumed ethanol for 30 days (Group B). Following the injection of 1 g ethanol/kg, arterial blood acetaldehyde levels reached levels of 150 and 300 microM for disulfiram and cyanamide respectively, values which were virtually identical regardless of the length of prior ethanol intake of the animals. Chronic ethanol intake in high-drinker rats leads to marked tolerance to the aversive effects of disulfiram and cyanamide on ethanol intake despite the presence of consistently high levels of blood acetaldehyde. These findings may have implications for the use of disulfiram for the treatment of alcoholism in humans.

Transcatheter Arterial Embolization of Renal VX-2 Carcinoma: Ethiodol-Ethanol Capillary Embolization Combined with Carboplatin

PubMed Central

Choi, Byung Gil; Van Pelt, Carolyn S.; Wright, Kenneth C.

2007-01-01

Objective We wanted to determine whether transcatheter Ethiodol-based capillary embolization in combination with carboplatin could improve the efficiency of a 1:1 Ethiodol-ethanol mixture (EEM) to ablate kidneys that been inoculated with VX-2 carcinoma. Materials and Methods The right kidney in 34 New Zealand white rabbits were inoculated with fresh VX-2 tumor fragments. One week later, the kidneys were subjected to transarterial treatment (4-5 rabbits/group): Saline infusion (Group 1); carboplatin infusion (5 or 10 mg, Groups 2A and 2B); carboplatin-Ethiodol (CE) alone (Group 3) and followed by main renal artery occlusion with ethanol (RAO) (Group 4); carboplatin-EEM (C-EEM) followed by RAO (Group 5); carboplatin infusion followed by EEM plus RAO (Group 6); and EEM followed by RAO (Group 7). The animals were followed for up to 3-weeks. The treated kidneys were evaluated angiographically and macroscopically. The kidneys that showed successful embolization macroscopically were entirely cut into serial sections, and these were examined microscopically. Histologically, the kidneys were evaluated on the basis of the residual tumor found in the serial sections. Results The results obtained with carboplatin infusion alone (Groups 2A and 2B) and CE without RAO (Group 3) were similar to those of the control animals (Group 1). Kidneys from Groups 4-7 demonstrated macroscopically successful embolization with histologically proven complete renal parenchyma infarction; however, some residual tumor was evident in all but one animal. Conclusion None of the Ethiodol-based modalities combined with locoregional carboplatin were more efficacious for tumor ablation than EEM alone. PMID:17420631

Preference for ethanol in feeding and oviposition in temperate and tropical populations of Drosophila melanogaster

PubMed Central

Zhu, Jing; Fry, James D.

2018-01-01

The natural habitat of Drosophila melanogaster Meigen (Diptera: Drosophilidae) is fermenting fruits, which can be rich in ethanol. For unknown reasons, temperate populations of this cosmopolitan species have higher ethanol resistance than tropical populations. To determine whether this difference is accompanied by a parallel difference in preference for ethanol, we compared two European and two tropical African populations in feeding and oviposition preference for ethanol-supplemented medium. Although females of all populations laid significantly more eggs on medium with ethanol than on control medium, preference of European females for ethanol increased as ethanol concentration increased from 2 to 6%, whereas that of African females decreased. In feeding tests, African females preferred control medium over medium with 4% ethanol, whereas European females showed no preference. Males of all populations strongly preferred control medium. The combination of preference for ethanol in oviposition, and avoidance or neutrality in feeding, gives evidence that adults choose breeding sites with ethanol for the benefit of larvae, rather than for their own benefit. The stronger oviposition preference for ethanol of temperate than tropical females suggests that this benefit may be more important in temperate populations. Two possible benefits of ethanol for which there is some experimental evidence are cryoprotection and protection against natural enemies. PMID:29398715

Sclerotherapy of renal cysts using acetic acid: a comparison with ethanol sclerotherapy.

PubMed

Cho, D S; Ahn, H S; Kim, S I; Kim, Y S; Kim, S J; Jeon, G S; Won, J H

2008-12-01

This study compared percutaneous sclerotherapy using 50% acetic acid with that using 99% ethanol for patients with simple renal cysts. The study included 72 simple renal cysts in 64 patients (male/female ratio = 31/33; age range, 31-75 years). Under fluoroscopic guidance, the cyst fluid was aspirated completely. Sclerotherapy was then performed using 50% acetic acid for 32 cysts and 99% ethanol for 40 cysts. The volumes of each renal cyst before and after sclerotherapy were compared using ultrasonography or CT. Medical records were reviewed to analyse any complications. The mean follow-up period was 21.5 months (range, 3-75 months). The mean remnant volume of the cyst after sclerotherapy was 2.6% of the initial volume in the acetic acid group and 14.0% in the ethanol group. The rates of complete remission, partial remission and treatment failure were 90.6%, 9.4% and 0%, respectively, in the acetic acid group, and 60.0%, 30.0% and 10.0%, respectively, in the ethanol group. There were no complications related to sclerotherapy in either group. In conclusion, acetic acid is a safe and effective sclerosing agent, with clinical results superior to those of ethanol, and is an alternative to ethanol for sclerotherapy of renal cysts.

Dose-response study of sajabalssuk ethanol extract from Artemisia princeps Pampanini on blood glucose in subjects with impaired fasting glucose or mild type 2 diabetes.

PubMed

Choi, Ji-Young; Shin, Su-Kyung; Jeon, Seon-Min; Baek, Nam-In; Chung, Hae-Gon; Jeong, Tae-Sook; Lee, Kyung Tae; Lee, Mi-Kyung; Choi, Myung-Sook

2011-01-01

Previously we reported that an ethanol extract from Artemisia princeps Pampanini lowered blood glucose in db/db mice. Here we report a preliminary study in which the blood glucose-lowering effects of two different doses of sajabalssuk ethanol extract (SBE), containing eupatilin and jaseocidin, were examined in hyperglycemic subjects with fasting blood glucose (FBG) levels of 100-150 mg/dL. Subjects were randomized into four groups: negative control (2,000 mg of lactose /day), positive control (1,140 mg of pinitol/day), low-dose SBE (2,000 mg of SBE/day), and high-dose SBE (4,000 mg of SBE/day). After 8 weeks of supplementation, FBG and glycosylated hemoglobin levels were significantly lowered in low-and high-dose SBE groups compared to the baseline values; high-dose SBE also resulted in significantly lower plasma free fatty acid levels and systolic blood pressure. This study demonstrated that supplementation of 2 g or 4 g of SBE daily can significantly reduce blood glucose in hyperglycemic subjects, although high-dose SBE seemed to be more effective than low-dose SBE for lowering plasma free fatty acid level and systolic blood pressure.

Increased Sensitivity to Alcohol Induced Changes in ERK Map Kinase Phosphorylation and Memory Disruption in Adolescent as Compared to Adult C57BL/6J Mice

PubMed Central

Spanos, Marina; Besheer, Joyce; Hodge, Clyde W.

2012-01-01

Adolescence is a critical period of brain development that is accompanied by increased probability of risky behavior, such as alcohol use. Emerging research indicates that adolescents are differentially sensitive to the behavioral effects of acute ethanol as compared to adults but the neurobiological mechanisms of this effect remain to be fully elucidated. This study was designed to evaluate effects of acute ethanol on extracellular signal-regulated kinase phosphorylation (p-ERK1/2) in mesocorticolimbic brain regions. We also sought to determine if age-specific effects of ethanol on p-ERK1/2 are associated with ethanol-induced behavioral deficits on acquisition of the hippocampal-dependent novel object recognition (NOR) test. Adolescent and adult C57BL/6J mice were administered acute ethanol (0 0.5, 1, or 3 g/kg, i.p.). Brains were removed 30-min post injection and processed for analysis of p-ERK1/2 immunoreactivity (IR). Additional groups of mice were administered ethanol (0 or 1 g/kg) prior to the NOR test. Analysis of p-ERK1/2 IR showed that untreated adolescent mice had significantly higher levels of p-ERK1/2 IR in the nucleus accumbens shell, basolateral amygdala (BLA), central amygdala (CeA), and medial prefrontal cortex (mPFC) as compared to adults. Ethanol (1 g/kg) selectively reduced p-ERK1/2 IR in the dentate gyrus and increased p-ERK1/2 IR in the BLA only in adolescent mice. Ethanol (3 g/kg) produced the same effects on p-ERK1/2 IR in both age groups with increases in CeA and mPFC, but a decrease in the dentate gyrus, as compared to age-matched saline controls. Pretreatment with ethanol (1 g/kg) disrupted performance on the NOR test specifically in adolescents, which corresponds with the ethanol-induced inhibition of p-ERK1/2 IR in the hippocampus. These data show that adolescent mice have differential expression of basal p-ERK1/2 IR in mesocorticolimbic brain regions. Acute ethanol produces a unique set of changes in ERK1/2 phosphorylation in the adolescent brain that are associated with disruption of hippocampal-dependent memory acquisition. PMID:22348893

Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain.

PubMed

Duncan, Jeremy; Wang, Niping; Zhang, Xiao; Johnson, Shakevia; Harris, Sharonda; Zheng, Baoying; Zhang, Qinli; Rajkowska, Grazyna; Miguel-Hidalgo, Jose Javier; Sittman, Donald; Ou, Xiao-Ming; Stockmeier, Craig A; Wang, Jun Ming

2015-07-01

Major depressive disorder and alcoholism are significant health burdens that can affect executive functioning, cognitive ability, job responsibilities, and personal relationships. Studies in animal models related to depression or alcoholism reveal that the expression of Krüppel-like factor 11 (KLF11, also called TIEG2) is elevated in frontal cortex, which suggests that KLF11 may play a role in stress- or ethanol-induced psychiatric conditions. KLF11 is a transcriptional activator of monoamine oxidase A and B, but also serves other functions in cell cycle regulation and apoptotic cell death. In the present study, immunohistochemistry was used to quantify intensity of nuclear KLF11, combined with an unbiased stereological approach to assess nuclei in fronto-limbic, limbic, and other brain regions of rats exposed chronically to social defeat or ethanol. KLF11 immunoreactivity was increased significantly in the medial prefrontal cortex, frontal cortex, and hippocampus of both stressed rats and rats fed ethanol. However, expression of KLF11 protein was not significantly affected in the thalamus, hypothalamus, or amygdala in either treatment group compared to respective control rats. Triple-label immunofluorescence revealed that KLF11 protein was localized in nuclei of neurons and astrocytes. KLF11 was also co-localized with the immunoreactivity of cleaved caspase-3. In addition, Western blot analysis revealed a significant reduction in anti-apoptotic protein, Bcl-xL, but an increase of caspase-3 expression in the frontal cortex of ethanol-treated rats compared to ethanol-preferring controls. Thus, KLF11 protein is up-regulated following chronic exposure to stress or ethanol in a region-specific manner and may contribute to pro-apoptotic signaling in ethanol-treated rats. Further investigation into the KLF11 signaling cascade as a mechanism for neurotoxicity and cell death in depression and alcoholism may provide novel pharmacological targets to lessen brain damage and maximize neuroprotection in these disorders.

Role of an Ethanolic Extract of Crotalaria juncea L. on High-Fat Diet-Induced Hypercholesterolemia.

PubMed

Kumar, Dinakaran Sathis; David, Banji; Harani, Avasarala; Vijay, Bhaskar

2014-01-01

To evaluate the antihypercholesterolemic effects of 50 mg/kg BW and 100 mg/kg BW per day of an ethanolic extract of Crotalaria juncea Linn (whole plant) by performing in vivo studies. The effects of oral administration of 50 mg/kg BW and 100 mg/kg BW per day of an ethanolic extract of Crotalaria juncea Linn (whole plant) in rats fed with a high-fat diet were investigated by evaluating parameters like food consumption, weight gain, fecal fat excretion, serum and liver lipids, and biochemical profiles as well as by histopathological studies. The results were compared to animals fed with the standard diet and animals fed with a high-fat diet and atorvastatin (10 mg/kg BW). The animal group administered with the ethanolic extract for 35 days showed decreased levels of TC, LDL, VLDL, TG, HDL+VLDL, VLDL+LDL, LDL/TC, AI, SGOT, SGPT, and elevated levels of HDL, HDL/TC, significantly (p<0.01 & p<0.05) in a dose-dependent manner. The evaluation of liver tissues of the animal groups treated with the herbal extract and standard had shown increased levels of SOD, GSH, and catalase, whereas levels of SGOT, SGPT, total glucose, HMG-CoA, lipase, amylase, and the percentage of malon-dialdehyde were decreased when compared with the high-fat diet-fed rats. Body weight and food intake in the treated groups were significantly lower than that in the model control. The present study showed that an ethanolic extract of Crotalaria juncea L. influences several blood lipid and metabolic parameters in rats, suggesting a potential benefit as an antihypercholesterolemic agent.

Neurolaena lobata L. promotes wound healing in Sprague Dawley rats

PubMed Central

Nayak, Bijoor Shivananda; Ramlogan, Surrin; Chalapathi Rao, AV; Maharaj, Sandeep

2014-01-01

Background: The leaves of the Neurolaena lobata (Asteraceae) plant are used to control diabetes and heal wounds and infections. Aim: The ethanolic extract of N. lobata leaf was evaluated for its ability to heal inflicted wounds in rats using the excision wound model. Materials and Methods: Animals were divided into three groups of six each. Test group animals were treated topically with an ethanolic extract of N. lobata (1:1 with petroleum jelly, 100 mg/kg/day). Standard and control group animals were treated with mupirocin and petroleum jelly, respectively. Treatment was given for 13 days and the wound area was measured on alternate days. Parameters of healing assessed were the rate of wound contraction, period of epithelialization and hydroxyproline content. Antimicrobial activity of the extract was observed against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Results: Phytochemical analysis of the extract showed the presence of saponins, tannins, alkaloids and flavanoids. Extract-treated animals exhibited 87% reduction in the wound area over 13 days when compared with the control (78%) and standard (83%) groups (P < 0.05). A significant decrease in the epithelialization period was noticed with the extract-treated test group animals compared with the controls and the standard group animals (P < 0.008). The hydroxyproline content of the extract-treated animals was higher (230.5 ± 42.1) when evaluated against the control and (79.0 ± 32.2) and the standard (115.0 ± 44.5) groups (P < 0.05). Conclusion: Increase in the rate of wound contraction and hydroxyproline content with decrease in epithelialization time in extract-treated animals support further evaluation of N. lobata as a pharmacotherapy for wound healing. PMID:25143886

The Mitochondria-targeted ubiquinone MitoQ decreases ethanol-dependent micro and macro hepatosteatosis

PubMed Central

Chacko, Balu K; Srivastava, Anup; Johnson, Michelle; Benavides, Gloria A.; Chang, Mi Jung; Ye, Yaozu; Jhala, Nirag; Murphy, Michael P; Kalyanaraman, Balaraman; Darley-Usmar, Victor M.

2011-01-01

Chronic alcohol-induced liver disease results in inflammation, steatosis and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone, MitoQ, (5 & 25 mg/kg/d for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α) and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis and induction of CYP2E1. MitoQ had a minor on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities, it did however decrease hepatic steatosis in ethanol consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocks the increase in HIF1α in all ethanol-fed groups which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol associated mitochondrial ROS and several downstream effects of ROS/RNS production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependant HIF1α stabilization. PMID:21520201

Phosphatidylethanolamine N-methyltransferase activity is increased in rat intestinal brush-border membrane by chronic ethanol ingestion.

PubMed

Furtado, Valéria Cristina Soares; Takiya, Christina Maeda; Braulio, Valeria Bender

2002-01-01

Phosphatidylethanolamine N-methyltransferase (PEMT) catalyses the synthesis of phosphatidylcholine from phosphatidylethanolamine. The aim of this study was to evaluate the effect of chronic ethanol ingestion on PEMT activity in the jejunal brush-border membrane (BBM) of adequately nourished rats. For this purpose, rats were fed a liquid diet containing ethanol [ethanol-fed group (EFG)] or an isocaloric liquid diet without ethanol [pair-fed group (PFG)] for 4 weeks. Diet ingestion, body weight, nitrogen balance and urinary creatinine excretion were monitored during the experimental period, and serum transferrin levels were determined at the end. BBM was isolated for the determination of PEMT activity. PEMT activity was significantly increased in the jejunal BBM of the EFG. Nutritional parameters, however, did not differ between groups. The increase in PEMT activity may be attributed exclusively to chronic ethanol ingestion, since a major nutritional deficit was excluded.

Effects of ethanol and folic acid consumption during pregnancy and lactation on basal enzymatic secretion in the duodenal juice of offspring rats.

PubMed

Cano, Ma José; Murillo, Ma Luisa; Delgado, Ma José; Carreras, Olimpia

2003-09-01

Studies on duodenal juice enzyme activities were carried out on suckling Wistar rats born to dams given ethanol during gestation and suckling. The results were compared with offspring of dams given diets containing no ethanol. Comparisons were also made with offspring of dams given ethanol and folic acid supplementation to observe whether a folate supplement could sufficiently reverse the negative effect of ethanol consumption. The dams were fed increased amounts of ethanol (5% to 20%, vol/vol) in tap water for 4 wk. The maximum quantity, 20% ethanol, was given to the dams during pregnancy and lactation. Offspring animals were randomized into three groups: control (CG), ethanol treated (EG), and ethanol plus folic acid (EFG). Body weight at birth and at 21 d after birth and pancreatic weight were lower in offspring after ethanol treatment. Folic acid supplement increased these parameters in the EFG. Under basal conditions, decreases in amylase, lipase, and chymotrypsin activities in the duodenal juice after ethanol treatment were detected. Serum and urine amylase activities also decreased in the EG and EFG. These changes were different in the ethanol-treated progenitors. In these progenitors, ethanol treatment increased serum amylase levels. In the offspring, amylase activities in the EFG decreased with respect to the CG; however, an increase in the EG was observed. In dams the folic acid supplement did not significantly alter the serum amylase activities. Lipase and chymotrypsin activities in the EFG were similar to those in the EG. An increase of serum and urine amylase in the EFG with respect to the EG was found. Our findings indicated that, under basal conditions, ethanol treatment during gestation and lactation negatively affects the digestive function in offspring. The effects of ethanol were slightly attenuated in rats supplemented with folic acid for amylase activities. Although extrapolation from animal studies can be tenuous, the present findings may explain the use of folic acid in the prevention of damage induced by ethanol to increase the amylase levels to physiologic concentrations.

LARVICIDAL ACTIVITY OF PERESKIA BLEO (KUNTH) DC. (CACTACEAE) FRUIT ENDOCARP CRUDE AND FRACTIONATED EXTRACTS AGAINST AEDES AEGYPTI (L.) (DIPTERA: CULICIDAE).

PubMed

Thongwat, Damrongpan; Ganranoo, Lucksagoon; Chokchaisiri, Ratchanaporn

2014-11-01

The use of insecticides can cause adverse effects in vector control, a plant bio-insecticide is an advantageous substitute. Currently, the promising mosquito larvicidal activity from plant extracts has been reported worldwide, including Thailand. In this study, the endocarp of Pereskia bleo (Kunth) DC. fruit was extracted with distilled water and ethanol. Crudes and fractionated groups of the extracts were evaluated for their larvicidal efficacy against the 3rd instar larvae of Aedes aegypti. At 48 hours of exposure, it was found that the activities of the extracts were higher than 24-hour's. The ethanolic extracts showed stronger activities than the aqueous ones, indicating the lower LC50 values of both crude and fractionated group extracts. The most toxic activity was found in a fractionated group of the ethanolic extract, E-Gr3, with significantly lowest LC50 values of 707.94 and 223.12 ppm for 24- and 48-hour detection times, respectively. The bioassay results indicated the larvicidal property against the Ae. aegypti mosquito of the P. bleo plant extracts. A safety for non-target organisms or an action on other mosquito vectors of this plant, should be further investigated.

[The clinical study of percutaneous transhepatic radiofrequency ablation combined with tumor edge of percutaneous absolute ethanol injection on liver cancer adjacent to major blood vessels].

PubMed

Du, Jun-dong; Liu, Rong; Jiao, Hua-bo; Xiang, De-dong; Yin, Hui-nan; Li, Zhen-cai; Li, Tao; Zhu, Zi-man; Li, Zhan-liang

2011-05-01

To explore the effects of percutaneous transhepatic radiofrequency ablation (PRFA) combined with tumor edge of percutaneous absolute ethanol injection (PEI) on liver cancer adjacent to major blood vessels. Seventy five patients with liver cancer adjacent to major blood vessels were randomly divided into two groups: PRFA+PEI therapy group (38 cases) and PRFA control group (37 cases). Tumor necrosis rate, AFP levels, local recurrence rate, median for survival time and cum survival were used as the evaluation index to evaluate the efficacies of the two methods. Tumor necrosis rates of the therapy group and the control group were 84.2% and 54.1% (P < 0.01), respectively; AFP levels of therapy group and control group at 1, 3, 6 and 12 months after treatment were (105.0 ± 35.5) μg/L, (28.4 ± 4.3) μg/L, (58.6 ± 6.7) μg/L, (89.5 ± 12.5) μg/L and (137.2 ± 34.6) μg/L, (84.2 ± 18.4) μg/L, (106.6 ± 20.3) μg/L, (173.7 ± 32.0) μg/L, respectively. The rates of therapy group was significantly lower than of control group. Local recurrence rates of the therapy group and control group were 2.6%, 7.9%, 13.2% and 31.6% vs 10.8%, 21.6% , 40.5% and 62.1% (P < 0.05) at 3, 6, 12 and 24 months after treatment, respectively. Median for survival time of the therapy group and control group were 28.0 ± 2.8 months and 19.0 ± 3.6 months, respectively. Cum survival of the therapy group and control group were 84.2%, 78.9%, 60.5% and 31.6% vs 78.4%, 67.6%, 37.8% and 8.1% (P < 0.05) at 6, 12, 24 and 36 months after treatment, respectively. PEI as a supplementary treatment of PRFA can effectively improve the treatment of liver cancer adjacent to major blood vessels and significantly reduce the local recurrence rate and improve long-term survival rates.

Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats

PubMed Central

Ariffin, Azhar; Abdulla, Mahmood A.; Abdullah, Zanariah

2016-01-01

A series of new 2-(ethylthio)benzohydrazone derivatives (1–6) were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol-induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre-treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up-regulation of HSP70 and down-regulation of Bax protein in stained tissue section. PMID:27272221

Influence of Fat/Carbohydrate Ratio on Progression of Fatty Liver Disease and on Development of Osteopenia in Male Rats Fed Alcohol via Total Enteral Nutrition (TEN)

PubMed Central

Ronis, Martin J. J.; Mercer, Kelly; Suva, Larry J.; Vantrease, Jamie; Ferguson, Matthew; Hogue, William R.; Sharma, Neha; Cleves, Mario A.; Blackburn, Michael L.; Badger, Thomas M.

2014-01-01

Alcohol abuse is associated with the development of fatty liver disease and also with significant osteopenia in both genders. In this study, we examined ethanol-induced pathology in response to diets with differing fat/carbohydrate ratios. Male Sprague-Dawley rats were fed intragastrically with isocaloric liquid diets. Dietary fat content was either 5% (high carbohydrate, HC) or 45% (high fat, HF), with or without ethanol (12–13 g/kg/day). After 14, 28, or 65 days, livers were harvested and analyzed. In addition, bone morphology was analyzed after 65 days. HC rats gained more weight and had larger fat pads than HF rats with or without ethanol. Steatosis developed in HC + ethanol (HC+EtOH) compared to HF + ethanol (HF+EtOH) rats, accompanied by increased fatty acid (FA) synthesis and increased nuclear carbohydrate response element binding protein (ChREBP) (p < 0.05), but in the absence of effects on hepatic silent mating type information regulation 2 homolog (SIRT-1) or nuclear sterol regulatory binding element protein (SREBP-1c). Ethanol reduced serum leptin (p < 0.05) but not adiponectin. Over time, HC rats developed fatty liver independent of ethanol. FA degradation was significantly elevated by ethanol in both HC and HF groups (p < 0.05). HF+EtOH rats had increased oxidative stress from 28 days, increased necrosis compared to HF controls and higher expression of cytochromes P450, CYP2E1, and CYP4A1 compared to HC+EtOH rats (p < 0.05). In contrast, HC+EtOH rats had no significant increase in oxidative stress until day 65 with no observed increase in necrosis. Unlike liver pathology, no dietary differences were observed on ethanol-induced osteopenia in HC compared to HF groups. These data demonstrate that interactions between diet composition and alcohol are complex, dependent on the length of exposure, and are an important influence in development of fatty liver injury. Importantly, it appears that diet composition does not affect alcohol-associated skeletal toxicity. PMID:24581955

Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial.

PubMed

Gepner, Yftach; Golan, Rachel; Harman-Boehm, Ilana; Henkin, Yaakov; Schwarzfuchs, Dan; Shelef, Ilan; Durst, Ronen; Kovsan, Julia; Bolotin, Arkady; Leitersdorf, Eran; Shpitzen, Shoshana; Balag, Shai; Shemesh, Elad; Witkow, Shula; Tangi-Rosental, Osnat; Chassidim, Yoash; Liberty, Idit F; Sarusi, Benjamin; Ben-Avraham, Sivan; Helander, Anders; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Thiery, Joachim; Rudich, Assaf; Stampfer, Meir J; Shai, Iris

2015-10-20

Recommendations for moderate alcohol consumption remain controversial, particularly in type 2 diabetes mellitus (T2DM). Long-term randomized, controlled trials (RCTs) are lacking. To assess cardiometabolic effects of initiating moderate alcohol intake in persons with T2DM and whether the type of wine matters. 2-year RCT (CASCADE [CArdiovaSCulAr Diabetes & Ethanol] trial). (ClinicalTrials.gov: NCT00784433). Ben-Gurion University of the Negev-Soroka Medical Center and Nuclear Research Center Negev, Israel. Alcohol-abstaining adults with well-controlled T2DM. Patients were randomly assigned to 150 mL of mineral water, white wine, or red wine with dinner for 2 years. Wines and mineral water were provided. All groups followed a Mediterranean diet without caloric restriction. Primary outcomes were lipid and glycemic control profiles. Genetic measurements were done, and patients were followed for blood pressure, liver biomarkers, medication use, symptoms, and quality of life. Of the 224 patients who were randomly assigned, 94% had follow-up data at 1 year and 87% at 2 years. In addition to the changes in the water group (Mediterranean diet only), red wine significantly increased high-density lipoprotein cholesterol (HDL-C) level by 0.05 mmol/L (2.0 mg/dL) (95% CI, 0.04 to 0.06 mmol/L [1.6 to 2.2 mg/dL]; P < 0.001) and apolipoprotein(a)1 level by 0.03 g/L (CI, 0.01 to 0.06 g/L; P = 0.05) and decreased the total cholesterol-HDL-C ratio by 0.27 (CI, -0.52 to -0.01; P = 0.039). Only slow ethanol metabolizers (alcohol dehydrogenase alleles [ADH1B*1] carriers) significantly benefited from the effect of both wines on glycemic control (fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with fast ethanol metabolizers (persons homozygous for ADH1B*2). Across the 3 groups, no material differences were identified in blood pressure, adiposity, liver function, drug therapy, symptoms, or quality of life, except that sleep quality improved in both wine groups compared with the water group (P = 0.040). Overall, compared with the changes in the water group, red wine further reduced the number of components of the metabolic syndrome by 0.34 (CI, -0.68 to -0.001; P = 0.049). Participants were not blinded to treatment allocation. This long-term RCT suggests that initiating moderate wine intake, especially red wine, among well-controlled diabetics as part of a healthy diet is apparently safe and modestly decreases cardiometabolic risk. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, and red wine's effects also involve nonalcoholic constituents. European Foundation for the Study of Diabetes.

Red sorrel (Hibiscus Sabdariffa) prevents the ethanol-induced deficits of Purkinje cells in the cerebellum.

PubMed

Suryanti, S; Partadiredja, G; Atthobari, J

2015-01-01

The present study is aimed at investigating the possible protective effects of H. sabdariffa on ethanol-elicited deficits of motor coordination and estimated total number of the Purkinje cells of the cerebellums of adolescent male Wistar rats. Forty male Wistar rats aged 21 days were divided into five groups. Na/wtr group was given water orally and injected with normal saline intra peritoneally (ip). Eth/wtr group was given water orally and ethanol (ip). Another three experimental groups (Eth/Hsab) were given different dosages of H. sabdariffa and ethanol (ip). All groups were treated intermittently for the total period of treatment of two weeks. The motor coordination of rats was tested prior and subsequent to the treatments. The rats were euthanized, and their cerebellums were examined. The total number of Purkinje cells was estimated using physical fractionator method. Upon revolving drum test, the number of falls of rats increased following ethanol treatment. There was no significant difference between the total number of falls prior and subsequent to treatment in all Eth/Hsab groups. The estimated total number of Purkinje cells in Eth/Hsab groups was higher than in Eth/wtr group. H. sabdariffa may prevent the ethanol-induced deficits of motor coordination and estimated total number of Purkinje cells of the cerebellums in adolescent rats (Tab. 3, Fig. 1, Ref. 42).

Evidence for a causative role of N-methyl-D-aspartate receptors in an in vitro model of alcohol withdrawal hyperexcitability.

PubMed

Thomas, M P; Monaghan, D T; Morrisett, R A

1998-10-01

Synaptic mechanisms underlying hyperexcitability due to withdrawal from chronic ethanol exposure were investigated in a hippocampal explant model system using electrophysiological techniques. Whole-cell voltage clamp recordings from CA1 pyramidal cells demonstrated that acute ethanol exposure inhibited N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents by over 40%. Chronic ethanol exposure for 6 to 11 days at 35 or 75 mM induced no differences from control explants in the fast component of the population synaptic response (non-NMDAR-mediated). Prolonged field potential recordings (to 10 hr) were used to monitor the withdrawal process in vitro. Ethanol-exposed explants from both 35 and 75 mM groups displayed an increase (60% and 89%, respectively) in the NMDAR-mediated component of synaptic transmission on withdrawal from chronic exposure. Prolonged tonic-clonic electrographic seizure activity was consistently observed after ethanol withdrawal only after the increase in NMDAR function. This hyperexcitability was inhibited by the NMDAR antagonist D-2-amino-5-phosphonovaleric acid and returned once the NMDAR component was reestablished after antagonist washout. In situ hybridization studies suggest that expression of NR2B subunit mRNA may be enhanced in explants after chronic ethanol exposure. No lasting differences were observed in the NMDAR component after acute in vitro ethanol exposure and withdrawal. These data suggest that the occurance of ethanol withdrawal hyperexcitability in this system may be directly dependent on alterations in NMDAR function after chronic exposure. Since this region and others that contain ethanol sensitive NMDARs may serve as epileptic foci, long term alterations in NMDAR function may be expected to generate paroxysmal depolarizing shifts underlying ictal events after withdrawal from ethanol exposure.

A study of the anti-inflammatory effect of the leaves of Psidium guajava Linn. on experimental animal models

PubMed Central

Dutta, Sarmistha; Das, Swarnamoni

2010-01-01

Introduction: The aim is to study the anti-inflammatory effect of the ethanolic extract of the leaves of Psidium guajava(PGE) on experimental animal models. Materials and Methods: Fresh leaves were collected, air-dried, powdered, and percolated in 95% ethanol. Acute toxicity test was done according to OECD guidelines. Four groups of animals of either sex, weighing 150–200g of the species Rattus norvegicus were taken for the study (n = 6). Group A was taken as control (3% gum acacia in 10 mL/kg body weight), Group B as test group (PGE 250 mg/kg body weight), Group C as test group (PGE 500 mg/kg body weight), and Group D as standard (Aspirin 100 mg/kg body weight). The animals were studied for acute inflammation by Carrageenan-induced rat paw edema, subacute inflammation by Granuloma pouch method, and chronic inflammation by Freund’s adjuvant-induced arthritis method. Statistical analysis was done by one-way analysis of variance followed by multiple comparison tests. Results: In acute inflammation, there was significant inhibition of paw edema in Groups B, C, and D in comparison with Group A (P < 0.05). In subacute inflammation, there was significant inhibition of exudate formation in Groups B, C, and D in comparison to Group A (P < 0.05). In chronic inflammation, there was significant inhibition of paw edema and inhibition of weight reduction in Groups B, C, and D compared with Group A. Downregulation of arthritis index was also significant in Groups B, C, and D in comparison with Group A (P < 0.05). Conclusion: The ethanolic extract of PGE has significant anti-inflammatory activity. PMID:21589759

Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

PubMed

Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

2007-09-25

Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

Antiatherosclerotic effects of Artemisia princeps Pampanini cv. Sajabal in LDL receptor deficient mice.

PubMed

Han, Jong-Min; Kim, Min-Jung; Baek, Seung-Hwa; An, Sojin; Jin, Yue-Yan; Chung, Hae-Gon; Baek, Nam-In; Choi, Myung-Sook; Lee, Kyung-Tae; Jeong, Tae-Sook

2009-02-25

Antiatherosclerotic effects of ethanolic extracts of Artemisia princeps Pampanini cv. Sajabal (ESJ) were investigated in low-density lipoprotein receptor deficient (LDLR(-/-)) mice. The Western diet-induced high levels of total cholesterol and triglyceride were similar in the ESJ and control groups. However, circulating oxidized LDL was significantly decreased in the ESJ group (p < 0.05). ESJ also markedly decreased aortic expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), and reduced the aortic lesion formation and macrophage accumulation by 36.7% (p < 0.05) and 43% (p < 0.01) in the control group, respectively. Additionally, ESJ inhibited atherogenic properties with cytokine-induced surface expression of cell adhesion molecules, chemokines, and monocyte adhesion to the human umbilical vein endothelial cells (HUVECs), and simultaneously suppressed nuclear factor-kappaB (NF-kappaB) activation. These results suggest that ethanolic extracts of Artemisia princeps Pampanini cv. Sajabal contributes to the antiatherosclerotic and anti-inflammatory activities in LDLR(-/-) mice.

Effects of the Cynanchum wilfordii Ethanol Extract on the Serum Lipid Profile in Hypercholesterolemic Rats.

PubMed

Lee, Hye-Sung; Choi, Jun-Hyeok; Kim, Young-Eon; Kim, In-Ho; Kim, Byoung-Mok; Lee, Chang-Ho

2013-09-01

The purpose of this study was to investigate the effects of the ethanol extract of Cynanchum wilfordii (ECW) on the blood lipid profile of hypercholesterolemic rats. Thirty 7-week-old male Sprague-Dawley rats were allowed free access to either a normal diet (AIN-93 diet), or 1% high-cholesterol diet with or without 0.5% or 1% ECW for 5 weeks. After sacrifice, the rat serum lipid profile was analyzed. The diets containing ECW decreased body weight gains compared to the normal diet. Serum HDL-cholesterol levels of ECW-fed groups were significantly increased in the hypercholesterolemic groups and normal groups (P<0.05). When 1% ECW was fed to the normal group, total cholesterol level was increased. Moreover, treatment of ECW in hypercholesterolemic groups yielded a dose-dependent and highly significant decrease in the atherogenic index as compared to the control. These results suggest that intake of Cynanchum wilfordii may help reduce the risks of hypercholesterolemia by increasing blood HDL-cholesterol and lowering the atherogenic index.

Involvement of the mitochondrial permeability transition pore in chronic ethanol-mediated liver injury in mice

PubMed Central

King, Adrienne L.; Swain, Telisha M.; Mao, Zhengkuan; Udoh, Uduak S.; Oliva, Claudia R.; Betancourt, Angela M.; Griguer, Corrine E.; Crowe, David R.; Lesort, Mathieu

2013-01-01

Chronic ethanol consumption increases sensitivity of the mitochondrial permeability transition (MPT) pore induction in liver. Ca2+ promotes MPT pore opening, and genetic ablation of cyclophilin D (CypD) increases the Ca2+ threshold for the MPT. We used wild-type (WT) and CypD-null (CypD−/−) mice fed a control or an ethanol-containing diet to investigate the role of the MPT in ethanol-mediated liver injury. Ca2+-mediated induction of the MPT and mitochondrial respiration were measured in isolated liver mitochondria. Steatosis was present in WT and CypD−/− mice fed ethanol and accompanied by increased terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive nuclei. Autophagy was increased in ethanol-fed WT mice compared with ethanol-fed CypD−/− mice, as reflected by an increase in the ratio of microtubule protein 1 light chain 3B II to microtubule protein 1 light chain 3B I. Higher levels of p62 were measured in CypD−/− than WT mice. Ethanol decreased mitochondrial respiratory control ratios and select complex activities in WT and CypD−/− mice. Ethanol also increased CypD protein in liver of WT mice. Mitochondria from control- and ethanol-fed WT mice were more sensitive to Ca2+-mediated MPT pore induction than mitochondria from their CypD−/− counterparts. Mitochondria from ethanol-fed CypD−/− mice were also more sensitive to Ca2+-induced swelling than mitochondria from control-fed CypD−/− mice but were less sensitive than mitochondria from ethanol-fed WT mice. In summary, CypD deficiency was associated with impaired autophagy and did not prevent ethanol-mediated steatosis. Furthermore, increased MPT sensitivity was observed in mitochondria from ethanol-fed WT and CypD−/− mice. We conclude that chronic ethanol consumption likely lowers the threshold for CypD-regulated and -independent characteristics of the ethanol-mediated MPT pore in liver mitochondria. PMID:24356880

Hydrogen-deuterium substitution in solid ethanol by surface reactions at low temperatures

NASA Astrophysics Data System (ADS)

Oba, Yasuhiro; Osaka, Kazuya; Chigai, Takeshi; Kouchi, Akira; Watanabe, Naoki

2016-10-01

Ethanol (CH3CH2OH) is one of the most abundant complex organic molecules in star-forming regions. Despite its detection in the gas phase only, ethanol is believed to be formed by low-temperature grain-surface reactions. Methanol, the simplest alcohol, has been a target for observational, experimental, and theoretical studies in view of its deuterium enrichment in the interstellar medium; however, the deuterium chemistry of ethanol has not yet been an area of focus. Recently, deuterated dimethyl ether, a structural isomer of ethanol, was found in star-forming regions, indicating that deuterated ethanol can also be present in those environments. In this study, we performed laboratory experiments on the deuterium fractionation of solid ethanol at low temperatures through a reaction with deuterium (D) atoms at 10 K. Hydrogen (H)-D substitution, which increases the deuteration level, was found to occur on the ethyl group but not on the hydroxyl group. In addition, when deuterated ethanol (e.g. CD3CD2OD) solid was exposed to H atoms at 10 K, D-H substitution that reduced the deuteration level occurred on the ethyl group. Based on the results, it is likely that deuterated ethanol is present even under H-atom-dominant conditions in the interstellar medium.

Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome

PubMed Central

Kharbanda, Kusum K.; Todero, Sandra L.; King, Adrienne L.; Osna, Natalia A.; McVicker, Benita L.; Tuma, Dean J.; Wisecarver, James L.; Bailey, Shannon M.

2012-01-01

Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE) revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM : S-adenosylhomocysteine (SAH) ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection. PMID:22187660

The enteroinsular axis and endocrine pancreatic function in chronic alcohol consumers: evidence for early beta-cell hypofunction.

PubMed

Patto, R J; Russo, E K; Borges, D R; Neves, M M

1993-09-01

Chronic alcohol consumers may have, as judged by functional criteria, exocrine as well as endocrine pancreatic dysfunction, the latter represented by a decreased insulin response to an oral glucose load. To investigate whether this decreased insulin response was due to an ethanol-induced beta-cell dysfunction or to an ethanol-induced dysfunction of the enteroinsular axis, we determined glucose, insulin, and C-peptide plasma concentrations following an oral and an intravenous glucose load in 16 healthy volunteer nonalcohol consumers and in 10 chronic alcohol consumers. In each group, total integrated response for glucose did not significantly change whether glucose was given orally or intravenously, indicating isoglycemic glucose loads. The total integrated response values for insulin in the alcoholic group following both glucose loads as well as C-peptide plasma concentrations were significantly lower than in the control group. Moreover, in both groups the insulin TIR values following the oral glucose load were significantly greater than the values obtained following the intravenous glucose load, indicating an incretin effect. These results indicate that the decreased insulin response observed in alcoholics was not caused by a dysfunction of the enteroinsular axis because it also occurred following an intravenous glucose load, but by an ethanol-induced beta-cell dysfunction because C-peptide and insulin were proportionally decreased in this group.

Betaine attenuates chronic alcohol‑induced fatty liver by broadly regulating hepatic lipid metabolism.

PubMed

Yang, Wenjuan; Huang, Luming; Gao, Jinhang; Wen, Shilei; Tai, Yang; Chen, Meng; Huang, Zhiyin; Liu, Rui; Tang, Chengwei; Li, Jing

2017-10-01

Betaine has previously been demonstrated to protect the liver against alcohol‑induced fat accumulation. However, the mechanism through which betaine affects alcohol‑induced hepatic lipid metabolic disorders has not been extensively studied. The present study aimed to investigate the effect of betaine on alcoholic simple fatty liver and hepatic lipid metabolism disorders. A total of 36 rats were randomly divided into control, ethanol and ethanol + betaine groups. Liver function, morphological alterations, lipid content and tumor necrosis factor (TNF)‑α levels were determined. Hepatic expression levels of diacylglycerol acyltransferase (DGAT) 1, DGAT2, sterol regulatory element binding protein (SREBP)‑1c, SREBP‑2, fatty acid synthase (FAS), 3‑hydroxy‑3‑methyl‑glutaryl (HMG)‑CoA reductase, peroxisome proliferator-activated receptor λ coactivator (PGC)‑1α, adiponectin receptor (AdipoR) 1 and AdipoR2 were quantified. Serum and adipose tissue adiponectin levels were assessed using an enzyme‑linked immunoassay. The results demonstrated that alcohol‑induced ultramicrostructural alterations in hepatocytes, including the presence of lipid droplets and swollen mitochondria, were attenuated by betaine. Hepatic triglyceride, free fatty acid, total cholesterol and cholesterol ester contents and the expression of DGAT1, DGAT2, SREBP‑1c, SREBP‑2, FAS and HMG‑CoA reductase were increased following ethanol consumption, however were maintained at control levels following betaine supplementation. Alcohol‑induced decreases in hepatic PGC‑1α mRNA levels and serum and adipose tissue adiponectin concentrations were prevented by betaine. The downregulation of hepatic AdipoR1 which resulted from alcohol exposure was partially attenuated by betaine. No significant differences in liver function, TNF‑α, phospholipid and AdipoR2 levels were observed among the control, ethanol and ethanol + betaine groups. Overall, these results indicated that betaine attenuated the alcoholic simple fatty liver by improving hepatic lipid metabolism via suppression of DGAT1, DGAT2, SREBP‑1c, FAS, SREBP‑2 and HMG‑CoA reductase and upregulation of PGC‑1α.

Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice.

PubMed

Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Taguchi, Takehito; Yamaoka, Kiyonori

2017-09-01

Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Taste responses to monosodium glutamate after alcohol exposure.

PubMed

Wrobel, Elzbieta; Skrok-Wolska, Dominika; Ziolkowski, Marcin; Korkosz, Agnieszka; Habrat, Boguslaw; Woronowicz, Bohdan; Kukwa, Andrzej; Kostowski, Wojciech; Bienkowski, Przemyslaw; Scinska, Anna

2005-01-01

The aim of the present study was to evaluate the effects of acute and chronic exposure to alcohol on taste responses to a prototypic umami substance, monosodium glutamate (MSG). The rated intensity and pleasantness of MSG taste (0.03-10.0%) was compared in chronic male alcoholics (n = 35) and control subjects (n = 25). In a separate experiment, the effects of acute exposure of the oral mucosa to ethanol rinse (0.5-4.0%) on MSG taste (0.3-3.0%) were studied in 10 social drinkers. The alcoholic and control group did not differ in terms of the rated intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (P < 0.01) higher, i.e. worse, in the alcohol-dependent subjects. The difference remained significant after controlling for between-group differences in cigarette smoking and coffee drinking. Rinsing with ethanol did not alter either intensity or pleasantness of MSG taste in social drinkers. The present results suggest that: (i) neither acute nor chronic alcohol exposure modifies taste responses to MSG; (ii) alcohol dependence may be associated with deficit in threshold taste reactivity, as assessed by electrogustometry.

Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats.

PubMed

Thomas, Jennifer D; Garrison, Megan; O'Neill, Teresa M

2004-01-01

Children exposed to alcohol prenatally suffer from a variety of behavioral alterations, including hyperactivity and learning deficits. Given that women continue to drink alcohol during pregnancy, it is critical that effective interventions and treatments be identified. Previously, we reported that early postnatal choline supplementation can reduce the severity of learning deficits in rats exposed to alcohol prenatally. The present study examined whether choline supplementation can reduce the severity of behavioral alterations associated with alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4-9 via an artificial rearing procedure. Artificially reared and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4-30, whereas the other half received saline vehicle injections. On PD 31-34, after choline treatment was complete, activity level was monitored and, on PD 40-42, subjects were tested on a serial spatial discrimination reversal learning task. Subjects exposed to alcohol were significantly hyperactive compared to controls. The severity of ethanol-induced hyperactivity was attenuated with choline treatment. In addition, subjects exposed to ethanol during the neonatal period committed a significantly greater number of perseverative-type errors on the reversal learning task compared to controls. Exposure to choline significantly reduced the number of ethanol-related errors. Importantly, these behavioral changes were not due to the acute effects of choline, but were related to long-lasting organizational effects of early choline supplementation. These data suggest that early dietary interventions may reduce the severity of fetal alcohol effects.

Ethanolic extract of seabuckthorn (Hippophae rhamnoides L) prevents high-fat diet-induced obesity in mice through down-regulation of adipogenic and lipogenic gene expression.

PubMed

Pichiah, P B Tirupathi; Moon, Hye-Jung; Park, Jeong-Eun; Moon, Yeon-Jeong; Cha, Youn-Soo

2012-11-01

Phenolic compounds and flavonoids ameliorate bodyweight, blood glucose, and serum lipid profile. Since seabuckthorn (Hippophae rhamnoides L.) is known as a rich source of isoflavones and flavonoids, we hypothesized that ethanolic extract of seabuckthorn leaves (SL) may have anti-obesity and hypoglycemic effects. To investigate the effect of ethanolic extract of SL, 32 C57BL/6J mice were randomly divided into 4 dietary groups, containing 8 mice in each group: normal diet group; high-fat diet (HD) control group; high-fat diet with SL extract, 500 mg/kg body weight (BW) (SL1) group; and high-fat diet with SL extract, 1000 mg/kg BW (SL2) group. After 13 weeks, it was observed that oral administration of SL extract significantly reduced the energy intake; BW gain; epididymal fat pad weight; hepatic triglyceride, hepatic, and serum total cholesterol levels; and serum leptin levels in the SL groups compared to the HD group. However, differences in serum triglyceride and insulin levels in the SL groups were not significant in comparison to the HD group. The hepatic mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase 1 along with PPAR-γ were significantly increased in SL groups, whereas the level of acetyl-CoA carboxylase was significantly reduced in SL groups compared to HD group. Our results indicated that SL is effective in preventing BW gain and fat accumulation in the liver; it also reduced adipose tissue mass, hepatic lipid profile, and serum leptin level in the mouse. Together, these observations suggest that SL is a potential agent to study in the management of obesity and related disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

The Potency of Red Seaweed (Eucheuma cottonii) Extracts as Hepatoprotector on Lead Acetate-induced Hepatotoxicity in Mice.

PubMed

Wardani, Giftania; Farida, Nuraini; Andayani, Rina; Kuntoro, Mahmiah; Sudjarwo, Sri Agus

2017-01-01

Lead is one of the most toxic metals, producing severe organ damage in animals and humans. Oxidative stress is reported to play an important role in lead acetate-induced liver injury. This study was carried out to investigate the role of ethanol extract of Eucheuma cottonii in protecting against lead acetate-induced hepatotoxicity in male mice. The sample used fifty male mice which were divided into five groups: negative control (mice were given daily with Aquadest); positive control (mice were given daily with lead acetate 20 mg/kg body weight (BW) orally once in a day for 21 days); and the treatment group (mice were given E. cottonii extracts 200 mg, 400 mg, and 800 mg/kg BW orally once in a day for 25 days, and on the 4 th day, were given lead acetate 20 mg/kg BW 1 h after E. cottonii extract administration for 21 days). On day 25, the levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured. The data of SGOT, SGPT, ALP, MDA, SOD, and GPx were analyzed with one-way ANOVA, followed by least significant difference test. The results showed that oral administration of lead acetate 20 mg/kg BW for 21 days resulted in a significant increase in SGOT, SGPT, ALP, and MDA levels. Moreover, there was a significant decrease in SOD and GPx levels. Treatment with E. cottonii extracts of 800 mg/kg BW but not with 200 mg/kg BW and 400 mg/kg BW significantly ( P < 0.05) decreased the elevated SGPT, SGOT, ALP, and MDA levels as compared to positive control group. Treatment with E. cottonii extracts of 800 mg/kg BW also showed a significant increase in SOD and GPx levels as compared to positive control group. Treating mice with lead acetate showed different histopathological changes such as loss of the normal structure of hepatic cells, blood congestion, and fatty degeneration whereas animals treated with lead acetate and E. cottonii extracts showed an improvement in these changes and the tissue appeared with normal structures. It can be concluded that E. cottonii extracts could be a potent natural product and can provide a promising hepatoprotective effect against lead acetate-induced hepatotoxicity in mice. In summary, Oxidative stress reported to play an important role in lead acetate induced liver injury. The lead acetate treatment significantly increased the SGOT, SGPT, ALP, MDA, and decreased the antioxidant enzymes (SOD and GPx) in liver. The inhibition of antioxidant enzymes will increase free radicals in liver tissues and might induce liver injury in mice. The presence of ethanol extract of Eucheuma cottonii with lead acetate showed protective effects as attenuating lead acetate against its liver toxicity, and this may be due to the activity of ethanol extract of Eucheuma cottonii as antioxidant. The antioxidant enzymes (SOD and GPx) were increased, and MDA, SGOT, SGPT, ALP were decreased after ethanol extract of Eucheuma cottonii administration. The enzymatic activities (SOD and GPx) and MDA in mice can be used as biomarkers of heavy metal toxicity such as lead acetate. Histopathological view of liver sections in the lead acetate treated group showed the liver damage, as compared to the negative control group. However, administration of ethanol extract of Eucheuma cottonii significantly improved the histopathological in liver of lead acetate-treated mice. From the results of this study we concluded that the ethanol extract of Eucheuma cottonii could be a potent natural product provide a promising protective effect against lead acetate induced liver toxicity in mice. Abbreviations Used : SGOT: Serum Glutamic Oxaloacetic Transaminase, SGPT: Serum Glutamic Pyruvate Transaminase, ALP: Alkaline Phosphatase, MDA: Malondialdehyde, SOD: Superoxide Dismutase, GPx: Glutathione Peroxidase.

The Potency of Red Seaweed (Eucheuma cottonii) Extracts as Hepatoprotector on Lead Acetate-induced Hepatotoxicity in Mice

PubMed Central

Wardani, Giftania; Farida, Nuraini; Andayani, Rina; Kuntoro, Mahmiah; Sudjarwo, Sri Agus

2017-01-01

Background: Lead is one of the most toxic metals, producing severe organ damage in animals and humans. Oxidative stress is reported to play an important role in lead acetate-induced liver injury. Aim: This study was carried out to investigate the role of ethanol extract of Eucheuma cottonii in protecting against lead acetate-induced hepatotoxicity in male mice. Materials and Methods: The sample used fifty male mice which were divided into five groups: negative control (mice were given daily with Aquadest); positive control (mice were given daily with lead acetate 20 mg/kg body weight (BW) orally once in a day for 21 days); and the treatment group (mice were given E. cottonii extracts 200 mg, 400 mg, and 800 mg/kg BW orally once in a day for 25 days, and on the 4th day, were given lead acetate 20 mg/kg BW 1 h after E. cottonii extract administration for 21 days). On day 25, the levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured. The data of SGOT, SGPT, ALP, MDA, SOD, and GPx were analyzed with one-way ANOVA, followed by least significant difference test. Results: The results showed that oral administration of lead acetate 20 mg/kg BW for 21 days resulted in a significant increase in SGOT, SGPT, ALP, and MDA levels. Moreover, there was a significant decrease in SOD and GPx levels. Treatment with E. cottonii extracts of 800 mg/kg BW but not with 200 mg/kg BW and 400 mg/kg BW significantly (P < 0.05) decreased the elevated SGPT, SGOT, ALP, and MDA levels as compared to positive control group. Treatment with E. cottonii extracts of 800 mg/kg BW also showed a significant increase in SOD and GPx levels as compared to positive control group. Treating mice with lead acetate showed different histopathological changes such as loss of the normal structure of hepatic cells, blood congestion, and fatty degeneration whereas animals treated with lead acetate and E. cottonii extracts showed an improvement in these changes and the tissue appeared with normal structures. Conclusion: It can be concluded that E. cottonii extracts could be a potent natural product and can provide a promising hepatoprotective effect against lead acetate-induced hepatotoxicity in mice. SUMMARY In summary, Oxidative stress reported to play an important role in lead acetate induced liver injury. The lead acetate treatment significantly increased the SGOT, SGPT, ALP, MDA, and decreased the antioxidant enzymes (SOD and GPx) in liver. The inhibition of antioxidant enzymes will increase free radicals in liver tissues and might induce liver injury in mice. The presence of ethanol extract of Eucheuma cottonii with lead acetate showed protective effects as attenuating lead acetate against its liver toxicity, and this may be due to the activity of ethanol extract of Eucheuma cottonii as antioxidant. The antioxidant enzymes (SOD and GPx) were increased, and MDA, SGOT, SGPT, ALP were decreased after ethanol extract of Eucheuma cottonii administration. The enzymatic activities (SOD and GPx) and MDA in mice can be used as biomarkers of heavy metal toxicity such as lead acetate. Histopathological view of liver sections in the lead acetate treated group showed the liver damage, as compared to the negative control group. However, administration of ethanol extract of Eucheuma cottonii significantly improved the histopathological in liver of lead acetate-treated mice. From the results of this study we concluded that the ethanol extract of Eucheuma cottonii could be a potent natural product provide a promising protective effect against lead acetate induced liver toxicity in mice. Abbreviations Used: SGOT: Serum Glutamic Oxaloacetic Transaminase, SGPT: Serum Glutamic Pyruvate Transaminase, ALP: Alkaline Phosphatase, MDA: Malondialdehyde, SOD: Superoxide Dismutase, GPx: Glutathione Peroxidase. PMID:28827971

Saccharin fading is not required for the acquisition of alcohol self-administration, and can alter the dynamics of cue-alcohol memory reconsolidation.

PubMed

Puaud, Mickaël; Ossowska, Zofia; Barnard, Jordan; Milton, Amy L

2018-04-01

Animal models of alcohol-seeking are useful for understanding alcohol addiction and for treatment development, but throughput in these models is limited by the extensive pretraining required to overcome the aversive taste of ethanol. Work by Augier et al. (Psychopharmacology 231: 4561-4568, 2014) indicates that Wistar rats will self-administer alcohol without water deprivation, exposure to sweetened ethanol solutions or intermittent access to ethanol. We sought to replicate and extend the work of Augier et al. by comparing the acquisition of instrumental self-administration of ethanol in Lister-Hooded rats that had been previously saccharin faded (SF group) or not (NSF group). We also aimed to determine whether NMDA receptor antagonism with MK-801, given at memory reactivation, reduced subsequent ethanol-seeking behaviour in both groups of animals. Finally, we assessed the ethanol preference of SF and NSF rats using the two-bottle choice procedure. Both SF and NSF groups acquired instrumental self-administration of ethanol, though SF rats consumed fewer of the earned reinforcers. MK-801, given at memory reactivation, had different effects on NSF and SF rats: impairing the capacity of an ethanol-paired conditioned stimulus (CS) to support reinstatement in NSF rats, and enhancing it in SF rats. Finally, neither SF nor NSF rats showed a preference for ethanol. Our data support those of Augier et al. (Psychopharmacology 231: 4561-4568, 2014) that pretraining is unnecessary for rats to acquire instrumental self-administration of ethanol. Indeed, saccharin fading may produce a weaker memory that extinguishes more readily, thus accounting for the different effects of MK-801 on SF and NSF rats.

Periadolescent ethanol vapor exposure persistently reduces measures of hippocampal neurogenesis that are associated with behavioral outcomes in adulthood.

PubMed

Ehlers, C L; Liu, W; Wills, D N; Crews, F T

2013-08-06

Excessive alcohol consumption is prevalent among adolescents and may result in lasting neurobehavioral consequences. The use of animal models to study adolescent alcohol exposure has the advantage of allowing for the control necessary in order to evaluate the effects of ethanol on the brain and separate such effects from genetic background and other environmental insults. In the present study the effects of moderate ethanol vapor exposure, during adolescence, on measures of neurogenesis and behavioral measures were evaluated at two different times following ethanol withdrawal, in adulthood. The two groups of Wistar rats were both exposed to intermittent ethanol vapor (14 h on/10h off/day) for 35-36 days from PD 23 to PD 58 (average blood ethanol concentration: 163 mg%). In the first group, after rats were withdrawn from vapor they were subsequently assessed for locomotor activity, conflict behavior in the open field, and behaviors in the forced swim test (FST) and then sacrificed at 72 days of age. The second group of rats were withdrawn from vapor and injected for 5 days with Bromo-deoxy-Uridine (BrdU). Over the next 8 weeks they were also assessed for locomotor activity, conflict behavior in the open field, and behaviors in the FST and then sacrificed at 113/114 days of age. All rats were perfused for histochemical analyses. Ethanol vapor-exposed rats displayed hypoactivity in tests of locomotion and less anxiety-like and/or more "disinhibitory" behavior in the open field conflict. Quantitative analyses of immunoreactivity revealed a significant reduction in measures of neurogenesis, progenitor proliferation, as indexed by doublecortin (DCX), Ki67, and increased markers of cell death as indexed by cleaved caspase-3, and Fluoro-Jade at 72 days, and decreases in DCX, and increases in cleaved caspase-3 at 114 days in the ethanol vapor-exposed rats. Progenitor survival, as assessed by BrdU+, was reduced in the vapor-exposed animals that were sacrificed at 114 days. The reduction seen in DCX labeled in cell counts was significantly correlated with hypoactivity at 24h after withdrawal as well as less anxiety-like and/or more "disinhibitory" behavior in the open field conflict test at 2 and 8 weeks following termination of vapor exposure. These studies demonstrate that behavioral measures of disinhibitory behavior correlated with decreases in neurogenesis are all significantly and persistently impacted by periadolescent ethanol exposure and withdrawal in Wistar rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic ethanol feeding inhibits plasma levels of insulin-like growth factor-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sonntag, W.E.; Boyd, R.L.

1988-01-01

The purpose of this study was to determine whether the generalized catabolic effects of chronic ethanol may be associated with a decline in plasma of insulin-like growth factor-1 (IGF-1). Male Sprague-Dawley rats were fed a liquid diet containing 5% ethanol or pair-fed a diet made isocaloric with maltose-dextrin. Animals were maintained on this diet for either 12 days or 4.5 months. Another groups of animals were fed control diet ad libitum for 2 weeks. After 12 days of feeding, plasma concentrations of IGF-1 in ad libitum fed rats were 771 +/- 41 ng/ml which was greater than concentrations in eithermore » pair-fed or ethanol-fed rats. After 4.5 months of feeding, plasma levels of IGF-1 in ad libitum and pair-fed rats were similar to the 12 day study. However, a significant decrease in plasma levels of IGF-1 was observed in ethanol-fed animals over the 4.5 month period. Results of a similar study in rats fed a high-fat diet for 4.5 months were similar to those found with the low-fat diet.« less

First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

PubMed

Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

2017-03-01

Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T 2 * and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T 2 * and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T 2 * values vary throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 *throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

EFFECT OF CHRONIC INGESTION OF WINE ON THE GLYCEMIC, LIPID AND BODY WEIGHT HOMEOSTASIS IN MICE

PubMed Central

de BRITO-FILHO, Sebastião Barreto; de MOURA, Egberto Gaspar; dos SANTOS, Orlando José; SAUAIA-FILHO, Euler Nicolau; AMORIM, Elias; SANTANA, Ewaldo Eder Carvalho; BARROS-FILHO, Allan Kardec Dualibe; SANTOS, Rennan Abud Pinheiro

2016-01-01

ABSTRACT Background: The health benefits associated with moderate wine consumption, as with ethanol and phenolic compounds, include different mechanisms still little understandable. Aim: Evaluate glycemic and weight variations, and the deposit of triglycerides, cholesterol and liver glycogen with red wine consumption. Methods: 60 ApoE knockout mice were divided into three groups of 20: Wine Group (WG), Ethanol Group (EG) and Water Group (WAG). They received daily: WG 50 ml of wine and 50 ml water; EG 6 ml ethanol and WAG 94 ml of water. All groups were followed for four months. The food intake was monitored daily, in the period from eight to ten hours and held every five days. The measurement of water intake was also made every five days. The weighing of the animals took place every ten days. Results: The WG had higher weight increase as compared to the other groups. The concentration of hepatic triglyceride was higher in WG (57%) and the EG group was lower (31.6%, p<0.01) than the control. The concentration of cholesterol was lower in the WG (23.6%), as well as EG (24.5%, p<0.05). The concentration of glycogen was higher in WG (16%) and fasting blood glucose was higher in EG compared to the other groups but not both demonstrated a statistically significant difference. Conclusion: The WG increased triglyceride and WAG decreased cholesterol. The triglyceride may be increased due to the high caloric value of wine or some unknown property that led to significant increase in subcutaneous andretroperitoneal fat in mice. PMID:27759775

The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Tomoki, E-mail: s13220@u-shizuoka-ken.ac.jp; Morita, Akihito, E-mail: moritaa@u-shizuoka-ken.ac.jp; Mori, Nobuko, E-mail: morin@b.s.osakafu-u.ac.jp

2014-02-21

Highlights: • Ethanol administration increased GPD1 mRNA expression. • Ethanol administration increased glucose incorporation into TG glycerol moieties. • No increase in hepatic TG levels was observed in ethanol-injected GPD1 null mice. • We propose that GPD1 is required for ethanol-induced TG accumulation in the liver. - Abstract: Acute ethanol consumption leads to the accumulation of triglycerides (TGs) in hepatocytes. The increase in lipogenesis and reduction of fatty acid oxidation are implicated as the mechanisms underlying ethanol-induced hepatic TG accumulation. Although glycerol-3-phosphate (Gro3P), formed by glycerol kinase (GYK) or glycerol-3-phosphate dehydrogenase 1 (GPD1), is also required for TG synthesis, themore » roles of GYK and GPD1 have been the subject of some debate. In this study, we examine (1) the expression of genes involved in Gro3P production in the liver of C57BL/6J mice in the context of hepatic TG accumulation after acute ethanol intake, and (2) the role of GPD1 in the progression of ethanol-induced fatty liver using GPD1 null mice. As a result, in C57BL/6J mice, ethanol-induced hepatic TG accumulation began within 2 h and was 1.7-fold greater than that observed in the control group after 6 h. The up-regulation of GPD1 began 2 h after administering ethanol, and significantly increased 6 h later with the concomitant escalation in the glycolytic gene expression. The incorporation of {sup 14}C-labelled glucose into TG glycerol moieties increased during the same period. On the other hand, in GPD1 null mice carrying normal GYK activity, no significant increase in hepatic TG level was observed after acute ethanol intake. In conclusion, GPD1 and glycolytic gene expression is up-regulated by ethanol, and GPD1-mediated incorporation of glucose into TG glycerol moieties together with increased lipogenesis, is suggested to play an important role in ethanol-induced hepatic TG accumulation.« less

Hydroxyisohexyl 3-cyclohexene carboxaldehyde- known as Lyral: quantitative aspects and risk assessment of an important fragrance allergen.

PubMed

Johansen, J D; Frosch, P J; Svedman, C; Andersen, K E; Bruze, M; Pirker, C; Menné, T

2003-06-01

Hydroxyisohexyl 3-cyclohexene carboxaldehyde, also known as Lyral, is a fragrance ingredient identified as the cause of contact allergic reactions in 2-3% of eczema patients undergoing patch testing. Lyral has been included in the standard patch test series in many clinics due to its importance as an allergen. It has been used without restrictions in cosmetic products, until now. In the present study, the dose-response relationship of Lyral contact allergy was studied with doses relevant for normal exposure in cosmetic products. 18 eczema patients, who previously had given a positive patch test to Lyral 5% petrolatum, were included along with 7 control subjects. All cases were tested with a serial dilution of Lyral in ethanol 6% to 6 p.p.m and subjected to a 2-week, repeated open application test with a low dose of Lyral in ethanol. In the case of no reaction, this was followed by another 2 weeks of testing with a higher dose. The test was performed at the volar aspect of the forearm. In 16 of 18 cases (89%), a positive use test developed, 11 reacting to the low and 5 to the high concentration. None reacted to the vehicle control of ethanol applied to the contralateral arm. All controls were negative to both the test solutions of Lyral and the ethanol control. The difference between the test and the control group was statistically significant (Fisher's test, P < 0.001). It is concluded that Lyral at the current usage levels is inducing sensitization in the community. The same levels were shown to elicit allergic contact dermatitis in almost all sensitized individuals. A significant reduction in usage concentrations is recommended to prevent contact allergic reactions.

Circadian Activity Rhythms and Voluntary Ethanol Intake in Male and Female Ethanol-Preferring Rats: Effects of Long-Term Ethanol Access

PubMed Central

Rosenwasser, Alan M.; McCulley, Walter D.; Fecteau, Matthew

2014-01-01

Chronic alcohol (ethanol) intake alters fundamental properties of the circadian clock. While previous studies have reported significant alterations in free-running circadian period during chronic ethanol access, these effects are typically subtle and appear to require high levels of intake. In the present study we examined the effects of long-term voluntary ethanol intake on ethanol consumption and free-running circadian period in male and female, selectively bred ethanol-preferring P and HAD2 rats. In light of previous reports that intermittent access can result in escalated ethanol intake, an initial 2-week water-only baseline was followed by either continuous or intermittent ethanol access (i.e., alternating 15-day epochs of ethanol access and ethanol deprivation) in separate groups of rats. Thus, animals were exposed to either 135 days of continuous ethanol access or to five 15-day access periods alternating with four 15-day periods of ethanol deprivation. Animals were maintained individually in running-wheel cages under continuous darkness throughout the experiment to allow monitoring of free-running activity and drinking rhythms, and 10% (v/v) ethanol and plain water were available continuously via separate drinking tubes during ethanol access. While there were no initial sex differences in ethanol drinking, ethanol preference increased progressively in male P and HAD2 rats under both continuous and intermittent-access conditions, and eventually exceeded that seen in females. Free-running period shortened during the initial ethanol-access epoch in all groups, but the persistence of this effect showed complex dependence on sex, breeding line, and ethanol-access schedule. Finally, while females of both breeding lines displayed higher levels of locomotor activity than males, there was little evidence for modulation of activity level by ethanol access. These results are consistent with previous findings that chronic ethanol intake alters free-running circadian period, and show further that the development of chronobiological tolerance to ethanol may vary by sex and genotype. PMID:25281289

Ethanol induced hepatic mitochondrial dysfunction is attenuated by all trans retinoic acid supplementation.

PubMed

Nair, Saritha S; Prathibha, P; Rejitha, S; Indira, M

2015-08-15

Alcoholics have reduced vitamin A levels in serum since vitamin A and ethanol share the same metabolic pathway. Vitamin A supplementation has an additive effect on ethanol induced toxicity. Hence in this study, we assessed the impact of supplementation of all trans retinoic acid (ATRA), an active metabolite of vitamin A on ethanol induced disruptive alterations in liver mitochondria. Male Sprague Dawley rats were grouped as follows: I: Control; II: Ethanol (4 g/kg b.wt./day); III: ATRA (100 μg/kg b.wt./day); and IV: Ethanol (4 g/kg b.wt./day)+ATRA (100 μg/kg b.wt./day). Duration of the experiment was 90 days, after which the animals were sacrificed for the study. The key enzymes of energy metabolism, reactive oxygen species, mitochondrial membrane potential and hepatic mRNA expressions of Bax, Bcl-2, c-fos and c-jun were assessed. Ethanol administration increased the reactive oxygen species generation in mitochondria. It also decreased the activities of the enzymes of citric acid cycle and oxidative phosphorylation. ATP content and mitochondrial membrane potential were decreased and cytosolic cytochrome c was increased consequently enhancing apoptosis. All these alterations were altered significantly on ATRA supplementation along with ethanol. These results were reinforced by our histopathological studies. ATRA supplementation to ethanol fed rats, led to reduction in oxidative stress, decreased calcium overload in the matrix and increased mitochondrial membrane potential, which might have altered the mitochondrial energy metabolism and elevated ATP production thereby reducing the apoptotic alterations. Hence ATRA supplementation seemed to be an effective intervention against alcohol induced mitochondrial dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Developmental ethanol exposure impairs locomotor movement in Japanese medaka (Oryzias latipes) larvae targeting epigenome.

PubMed

Dasmahapatra, Asok K; Carty, Dennis R; Khan, Ikhlas A

2017-11-01

Evidence indicated ethanol exposure during development disrupts brain functions that induces fetal alcohol spectrum disorder (FASD) phenotypes with behavioral abnormalities. We aimed to investigate whether prenatal ethanol exposure has any potential impact on behavior of a FASD fish model. Fertilized Japanese medaka (Oryzias latipes) eggs were exposed to 100-300 mM ethanol or 2 mM 5-azacytidine (5-azaC), 0-2 day post fertilization (dpf), in embryo-rearing medium (ERM). Survived embryos were maintained in clean ERM and used either for gene expression analysis on 2- and 6-dpf or allowed to hatch for behavioral study. Photomotor response of 3-4 day post hatch larvae were tracked for 3 h with light-dark transitions. It was observed that larval swimming was phototactic; enhanced in presence of light, declined in dark. Phototactic response was also observed in larvae prenatally exposed to ethanol or 5-azaC; however, the total distance swum by these larvae compared to controls declined. Further analysis indicated that, in light phases, total swimming activity and average swimming speed were reduced in larvae prenatally exposed to ethanol (300 mM) or 5-azaC. Expression analysis of baz1a and baz2a in embryos indicated developmental regulation. Ethanol (100-300 mM) or 5-azaC (2 mM) were able to modulate downregulation of both baz1a and baz2a mRNAs only in 6 dpf embryos of 300 mM ethanol and 5-azaC (2 mM) groups. These studies indicated that prenatal exposure to ethanol or 5-azaC was able to disrupt movements and thus swimming behavior in FASD phenotypes probably due to delayed remodeling of genome and epigenome. Published by Elsevier Ltd.

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.

PubMed

Chen, Grace; Nomikos, George G; Affinito, John; Zhao, Zhen

2016-09-01

Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium. This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium. Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine. Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.

Effects of S-Adenosylmethionine and Its Combinations With Taurine and/or Betaine on Glutathione Homeostasis in Ethanol-induced Acute Hepatotoxicity

PubMed Central

Lee, Seo Yeon; Ko, Kwang Suk

2016-01-01

Background Exposure to ethanol abuse and severe oxidative stress are risk factors for hepatocarcinoma. The aim of this study was to evaluate the effects of S-adenosylmethionine (SAMe) and its combinations with taurine and/or betaine on the level of glutathione (GSH), a powerful antioxidant in the liver, in acute hepatotoxicity induced by ethanol. Methods To examine the effects of SAMe and its combinations with taurine and/or betaine on ethanol-induced hepatotoxicity, AML12 cells and C57BL/6 mice were pretreated with SAMe, taurine, and/or betaine, followed by ethanol challenge. Cell viability was detected with an MTT assay. GSH concentration and mRNA levels of GSH synthetic enzymes were measured using GSH reductase and quantitative real-time reverse transcriptase-PCR. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with commercially available kits. Results Pretreatment of SAMe, with or without taurine and/or betaine, attenuated decreases in GSH levels and mRNA expression of the catalytic subunit of glutamate-cysteine ligase (GCL), the rate-limiting enzyme for GSH synthesis, in ethanol-treated cells and mice. mRNA levels of the modifier subunit of GCL and glutathione synthetase were increased in mice treated with SAMe combinations. SAMe, taurine, and/or betaine pretreatment restored serum ALT and AST levels to control levels in the ethanol-treated group. Conclusions Combinations of SAMe with taurine and/or betaine have a hepatoprotective effect against ethanol-induced liver injury by maintaining GSH homeostasis. PMID:27722142

Side draw control design for a high purity multi-component distillation column.

PubMed

A Udugama, Isuru; Munir, M T; Kirkpatrick, Rob; Young, Brent R; Yu, Wei

2018-05-01

Industrial methanol production involves a multi component feed containing methanol, water and trace levels of ethanol being refined to produce AA grade methanol at high product recovery. Due to practical constraints, the bottoms discharge of the column is primarily water with only trace of methanol impurities. As a result of these constraints, ethanol, which is a non-key middle boiling component gets "trapped" near the side draw of the column forming an ethanol bulge, which in turn results in non-linear, inverse, time and state varying behaviour of the side draw ethanol composition. In this work, we established that the existence of the ethanol bulge creates the complex process behaviour of the side draw ethanol composition and that this bulge needs to be explicitly controlled. This type of explicit composition bulge analysis and subsequent control has not been attempted on methanol distillation columns before. For this purpose a novel, robust and practical side draw control scheme to detect and remedy the excess ethanol bulge movement using override control is presented. The side draw controller, together with other regulatory controllers is shown to maintain on-specification operations of the column. Disturbance rejection tests carried out illustrate that the side draw control scheme will keep the column operating within commercial specification. It is also shown that a traditional DV control structure is unable to achieve this objective. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth

PubMed Central

Opoku-Acheampong, Alexander B.; Penugonda, Kavitha; Lindshield, Brian L.

2016-01-01

Saw palmetto supplements (SPS) are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP) SPS ≥ 750 nM with testosterone significantly increased and ≥500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP) SPS ≥ 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP) SPS ≥ 750 nM or with androgens significantly decreased LNCaP cell number (n = 3; p < 0.05). Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n = 4), HLLP, HLHP, and HMLP SPS (n = 6) groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p < 0.05). Results may suggest that SPS inhibit 5α-reductase thereby preventing hamster flank organ growth. PMID:27272436

Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth.

PubMed

Opoku-Acheampong, Alexander B; Penugonda, Kavitha; Lindshield, Brian L

2016-01-01

Saw palmetto supplements (SPS) are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP) SPS ≥ 750 nM with testosterone significantly increased and ≥500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP) SPS ≥ 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP) SPS ≥ 750 nM or with androgens significantly decreased LNCaP cell number (n = 3; p < 0.05). Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n = 4), HLLP, HLHP, and HMLP SPS (n = 6) groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p < 0.05). Results may suggest that SPS inhibit 5α-reductase thereby preventing hamster flank organ growth.

Effect of 95% Ethanol as a Final Irrigant before Root Canal Obturation in Primary Teeth: An in vitro Study.

PubMed

Thiruvenkadam, G; Asokan, Sharath; John, Baby; Priya, Pr Geetha

2016-01-01

Successful obturation in the primary teeth demands complete dryness of the root canal system. The purpose of this study was to determine the effect of 95% ethanol as the final irrigant before root canal obturation in primary teeth. A total of 20 extracted primary mandibular canines were biomechanically prepared and pre-obturated volume of each tooth was assessed using spiral computed tomography (CT). The specimens were divided into two groups (n = 10): group 1, Metapex group; group 2, zinc oxide eugenol group. Each group was further divided randomly into two subgroups (n = 5): subgroup 1, canals were dried with 95% ethanol; subgroup 2, canals were blot dried with paper points with the last one appearing dry. All canals were obturated and the postobturated volume of each tooth was measured. The percentage of obturated volume (POV) was calculated using the formula: (postobturated volume/preobturated volume) × 100. The POV between the groups was statistically analyzed using Mann-Whitney test and Wilcoxon Signed rank test appropriately. Root canals that were dried with ethanol showed better obturation than using paper points alone and the difference was statistically significant in both group 1 (p < 0.001) and group 2 (p < 0.002). Drying of the root canal system with 95% ethanol can result in better obturation in the primary teeth. How to cite this article: Thiruvenkadam G, Asokan S, John B, Geetha Priya PR. Effect of 95% Ethanol as a Final Irrigant before Root Canal Obturation in Primary Teeth: An in vitro Study. Int J Clin Pediatr Dent 2016;9(1):21-24.

Liver proteomics in progressive alcoholic steatosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernando, Harshica; Wiktorowicz, John E.; Soman, Kizhake V.

2013-02-01

Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber–DeCarli diet daily for 1 and 3 months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3 months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved inmore » alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3 months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (− 1.6) at 1 month and up regulation of aldehyde dehydrogenase (2.1) at 3 months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1 month) while peroxiredoxin-1 was down regulated (− 1.5) at late fatty liver stage (3 months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified D-dopachrome tautomerase (− 1.7, at 3 months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum. -- Graphical abstract: The figure shows the Hierarchial cluster analysis of differentially expressed protein spots obtained after ethanol feeding for 1 (1–3) and 3 (4–6) months. C and E represent pair-fed control and ethanol-fed rats, respectively. Highlights: ► Proteins related to ethanol-induced steatosis and mild steatohepatitis are identified. ► ADH1C and ALDH2 involved in alcohol metabolism are differentially expressed at 1 and 3 months. ► Discovery proteomics identified a group of proteins to serve as potential biomarkers. ► Using nonparametric analysis DDT is identified as a possible marker for liver damage.« less

[Ethanol changes sensitivity of Kupffer cells to endotoxin].

PubMed

Yamashina, Shunhei; Ikejima, Kenichi; Enomoto, Nobuyuki; Takei, Yoshiyuki; Sato, Nobuhiro

2003-10-01

Gut-derived endotoxin plays an important role in alcoholic liver injury. Intestinal sterilization with antibiotics (polymyxin B and neomycin) or inactivation of Kupffer cells with gadolinium chloride can prevent early alcohol-induced liver injury in the Tsukamoto-French model. Although short-term administration of alcohol enhances endotoxin hepatotoxicity, a majority of studies report that short-term ethanol inactivates Kupffer cells. It is therefore paradoxical that Kupffer cells are involved in alcoholic liver injury based on in vivo data with gadolinium chloride and antibiotics, yet ethanol blunts activation of isolated Kupffer cells. Accordingly, this review focuses on understanding this paradox by studying the temporal effect of ethanol in vivo on the response of subsequently isolated Kupffer cells. Mice were given ethanol intragastrically, and LPS was injected later. One hour after ethanol treatment, serum transaminases after LPS were 60% of control, while ethanol increased these parameters about 3-fold 21 hours after ethanol. Pretreatment with antibiotics blocked these effects of ethanol. Two hours after ethanol administration, the LPS-induced increases in intracellular calcium concentration and TNF alpha release by Kupffer cells was diminished by 50% of control, and these parameters were reciprocally enhanced two-fold at 24 hours. Sterilization of the gut with antibiotics blocked both effects of ethanol on intracellular calcium concentration and TNF alpha release. Twenty-four hours after ethanol, CD14 in Kupffer cells was elevated to about five-fold. In Kupffer cells from mice treated with ethanol 1 hour earlier, IRAK expression and activity and NF kappa B were decreased to 50-60% of control. In contrast, in Kupffer cells from mice treated with ethanol 21 hours earlier, LPS-induced TNF alpha production, expression and activity of IRAK were increased 1.5-fold over controls, while NF kappa B activation was elevated 3-fold. Kupffer cells isolated from rodents early after ethanol exhibited tolerance to LPS, whereas sensitization was observed later. In conclusion, acute ethanol alters the expression of endotoxin receptors and intracellular signaling molecules, and causes both tolerance and sensitization of Kupffer cells to endotoxin. It is postulated that tolerance of Kupffer cells contributes to the impairment of innate immune system in alcoholism, while sensitization to endotoxin enhances progression of alcoholic liver injury.

Nebulization with Gamma-Tocopherol Ameliorates Acute Lung Injury after Burn and Smoke Inhalation in the Ovine Model

PubMed Central

Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sousse, Linda E.; Sakurai, Hiroyuki; Rehberg, Sebastian W.; Asmussen, Sven; Kraft, Edward R.; Wright, Charlotte L.; Bartha, Eva; Cox, Robert A.; Hawkins, Hal K.; Traber, Lillian D.; Traber, Maret G.; Szabo, Csaba; Herndon, David N.; Traber, Daniel L.

2012-01-01

We hypothesize that the nebulization of gamma-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome (ARDS) will effectively improve pulmonary function following burn and smoke inhalation after 96 hours. Adult ewes (n=14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 hours after the injury (g-T group, n=6), while the control group (n=5) was nebulized with only ethanol. Animals were weaned from the ventilator when possible. All animals were sacrificed after 96 hours, with the exception of one untreated animal that was euthanized after 64 hours. Lung g-T concentration significantly increased after g-T nebulization compared to the control group (38.5±16.8 nmol/g vs. 0.39±0.46, p<0.01). The PaO2/FiO2 ratio was significantly higher after treatment with g-T compared to the control group (310±152 vs 150±27.0, p<0.05). The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9±0.87 vs 4.6±1.4, p<0.05), and bronchiolar obstruction (2.0±1.1% vs 4.6±1.7%, p<0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn and smoke injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of ALI patients who have sustained oxidative damage to the airway. PMID:22266978

Ethanol for preventing preterm birth in threatened preterm labor.

PubMed

Haas, David M; Morgan, Amanda M; Deans, Samantha J; Schubert, Frank P

2015-11-05

Preterm birth is the leading cause of death and disability in newborns worldwide. A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor. One of the earliest tocolytics utilized for this purpose was ethanol infusion, although this is not generally used in current practice due to safety concerns for both the mother and her baby. To determine the efficacy of ethanol in stopping preterm labor, preventing preterm birth, and the impact of ethanol on neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. We included randomized and quasi-randomized studies. Cluster-randomized trials and cross-over design trials were not eligible for inclusion. We only included studies published in abstract form if there was enough information on methods and relevant outcomes. Trials were included if they compared ethanol infusion to stop preterm labor versus placebo/control or versus other tocolytic drugs. At least two review authors independently assessed studies for inclusion and risk of bias. At least two review authors independently extracted data. Data were checked for accuracy. Twelve trials involving 1586 women met inclusion criteria for this review. One trial did not report on the outcomes of interest in this review.Risk of bias of included studies: The included studies generally were of low quality based on inadequate reporting of methodology. Only three trials had low risk of bias for random sequence generation and one had low risk of bias for allocation concealment and participant blinding. Most studies were either high risk of bias or uncertain in these key areas. Comparison 1: Ethanol versus placebo/control (two trials, 77 women) Compared to controls receiving pain medications and dextrose solution, ethanol did not improve any of the primary outcomes: birth < 48 hours after trial entry (one trial, 35 women; risk ratio (RR) 0.93, 95% confidence interval (CI) 0.43 to 2.00), or neonatal mortality (one trial, 35 women; RR 1.06, 95% CI 0.31 to 3.58). Serious maternal adverse events and perinatal mortality were not reported by either of the two trials in this comparison. Maternal adverse events (overall) were not reported but one trial (42 women) reported that there were no maternal adverse events that required stopping or changing drug) in either group. One trial did report delay until delivery but this outcome was reported as a median with no mention of the standard deviation (median 19 days in ethanol group versus "less than 1" day in the glucose/water group). There were no differences in any secondary outcomes reported: preterm birth < 34 weeks or < 37 weeks; serious infant outcome; fetal alcohol syndrome/fetal alcohol spectrum disorder; or small-for-gestational age. Comparison 2: Ethanol versus other tocolytic (betamimetics) (nine trials, 1438 women) Compared to betamimetics (the only tocolytic used as a comparator in these studies), ethanol was associated with no clear difference in the rate of birth < 48 hours after trial entry (two trials, 130 women; average RR 1.12, 95% CI 0.53 to 2.37, Tau² = 0.19, I² = 59%), similar rates of perinatal mortality (six trials, 698 women; RR1.20, 95% CI 0.78 to 1.84), higher rates of neonatal mortality (eight trials, 1238 women; RR 1.43, 95% CI 1.02 to 2.02), higher rates of preterm birth < 34 weeks (two trials, 599 women; RR 1.56, 95% CI 1.11 to 2.19), higher rates of neonatal respiratory distress syndrome (three trials, 823 women; RR 1.76, 95% CI 1.33 to 2.33), and higher rates of low birthweight babies < 2500 g (five trials, 834 women; RR 1.30, 95% CI 1.09 to 1.54). These outcomes are likely all related to the lower incidence of preterm birth seen with other tocolytics, which for all these comparisons were betamimetics. Serious maternal adverse events were not reported in any of the nine trial reports. However, ethanol had a trend towards a lower rate of maternal adverse events requiring stopping or changing the drug (three trials, 214 women; RR 0.25, 95% CI 0.06 to 0.97). There were no differences in other secondary outcomes of preterm birth < 37 weeks, number of days delivery was delayed, or overall maternal adverse events.Planned sensitivity analysis, excluding quasi-randomized trials did not substantially change the results of the primary outcome analyses with the exception of neonatal mortality which no longer showed a clear difference between the ethanol and other tocolytic groups (3 trials, 330 women; RR 1.49, 95% CI 0.82 to 2.72). This review is based on evidence from twelve studies which were mostly low quality. There is no evidence that to suggest that ethanol is an effective tocolytic compared to placebo. There is some evidence that ethanol may be better tolerated than other tocolytics (in this case betamimetics), but this result is based on few studies and small sample size and therefore should be interpreted with caution. Ethanol appears to be inferior to betamimetics for preventing preterm birth in threatened preterm labor.Ethanol is generally no longer used in current practice due to safety concerns for the mother and her baby. There is no need for new studies to evaluate the use of ethanol for preventing preterm birth in threatened preterm labour. However, it would be useful for long-term follow-up studies on the babies born to mothers from the existing studies in order to assess the risk of long-term neurodevelopmental status.

Improving Ethanol Tolerance of Escherichia coli by Rewiring Its Global Regulator cAMP Receptor Protein (CRP)

PubMed Central

Yeow, Jianwei; Wang, Ivy; Zhang, Hongfang; Song, Hao; Jiang, Rongrong

2013-01-01

A major challenge in bioethanol fermentation is the low tolerance of the microbial host towards the end product bioethanol. Here we report to improve the ethanol tolerance of E. coli from the transcriptional level by engineering its global transcription factor cAMP receptor protein (CRP), which is known to regulate over 400 genes in E. coli. Three ethanol tolerant CRP mutants (E1– E3) were identified from error-prone PCR libraries. The best ethanol-tolerant strain E2 (M59T) had the growth rate of 0.08 h−1 in 62 g/L ethanol, higher than that of the control at 0.06 h−1. The M59T mutation was then integrated into the genome to create variant iE2. When exposed to 150 g/l ethanol, the survival of iE2 after 15 min was about 12%, while that of BW25113 was <0.01%. Quantitative real-time reverse transcription PCR analysis (RT-PCR) on 444 CRP-regulated genes using OpenArray® technology revealed that 203 genes were differentially expressed in iE2 in the absence of ethanol, whereas 92 displayed differential expression when facing ethanol stress. These genes belong to various functional groups, including central intermediary metabolism (aceE, acnA, sdhD, sucA), iron ion transport (entH, entD, fecA, fecB), and general stress response (osmY, rpoS). Six up-regulated and twelve down-regulated common genes were found in both iE2 and E2 under ethanol stress, whereas over one hundred common genes showed differential expression in the absence of ethanol. Based on the RT-PCR results, entA, marA or bhsA was knocked out in iE2 and the resulting strains became more sensitive towards ethanol. PMID:23469036

Antioxidant and antihyperlipidemic effect of Solanum nigrum fruit extract on the experimental model against chronic ethanol toxicity

PubMed Central

Arulmozhi, Vadivel; Krishnaveni, Mani; Karthishwaran, Kandhan; Dhamodharan, Ganesan; Mirunalini, Sankaran

2010-01-01

The possible protective effect of Solanum nigrum fruit extract (SNFEt) was investigated for its antioxidant and antihyperlipidemic activity against ethanol-induced toxicity in rats. The experimental animals were intoxicated with 20% ethanol (7.9 g/kg/day) for 30 days via gastric intubation. SNFEt was administered at the dose of 250 mg/kg body weight along with the daily dose of ethanol for 30 days. From the result it was observed that ethanol-induced rats showed a significant elevation in the levels of Thiobarbituric acid reactive substances (TBARS), which lowered the antioxidant defense systems, such as, reduced glutathione (GSH) and vitamins C and E, when compared to the controls. In the lipid profiles, the levels of total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL), very low density lipoproteins (VLDL), free fatty acids (FFA), and phospholipids were significantly elevated in the ethanol-induced group, whereas, the high density lipoproteins (HDL) were found to be reduced in the plasma, and the phospholipid levels were significantly decreased in the tissues. Supplementation of SNFEt improved the antioxidant status by decreasing the levels of TBARS and altering the lipid profiles to near normal. These activities were also compared to the standard drug silymarin (25 mg/kg body weight). Thus the findings of the present study indicated a significant antioxidant and antihyperlipidemic activity of Solanum nigrum fruits, which offered protection against ethanol-induced toxicity. PMID:20548935

Extract of Allium tuberosum Rottler ex Spreng Promoted the Hair Growth through Regulating the Expression of IGF-1

PubMed Central

Park, Ki Moon; Kim, Dong Woo; Lee, Seung Ho

2015-01-01

Allium tuberosum Rottler ex Spreng (ATRES) has been used as a traditional medicine for the treatment of abdominal pain, diarrhea, and asthma. In this study, we investigated the hair growth promoting activities of ATRES on telogenic C57BL6/N mice. Hair growth was significantly increased in the dorsal skin of ethanol extract of ATRES treated mouse group compared with the control mouse group. To enrich the hair promoting activity, an ethanol-insoluble fraction was further extracted in sequence with n-hexane, dichloromethane, ethyl acetate, n-butanol, and distilled water. Interestingly, we found that extraction with n-butanol is most efficient in producing the hair promoting activity. In addition, the soluble fraction of the n-butanol extract was further separated by silica gel chromatography and thin layer chromatography (TLC) resulting in isolating four single fractions which have hair growth regeneration potential. Furthermore, administration of ATRES extracts to dorsal skin area increased the number of hair follicles compared with control mouse group. Interestingly, administration of ATRES extract stimulated the expression of insulin-like growth factor-1 (IGF-1) but not of keratin growth factor (KGF) or vascular endothelial growth factor (VEGF). Taken together, these results suggest that ATRES possesses strong hair growth promoting potential which controls the expression of IGF-1. PMID:26078771

Schiff base metal derivatives enhance the expression of HSP70 and suppress BAX proteins in prevention of acute gastric lesion.

PubMed

Golbabapour, Shahram; Gwaram, Nura Suleiman; Al-Obaidi, Mazen M Jamil; Soleimani, A F; Ali, Hapipah Mohd; Abdul Majid, Nazia

2013-01-01

Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP) 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg), the positive control (Tween 20 5% v/v, 5 mL/kg), and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg). After 1 h, all of the groups received ethanol 95% (5 mL/kg) but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg). The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E), immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats.

Schiff Base Metal Derivatives Enhance the Expression of HSP70 and Suppress BAX Proteins in Prevention of Acute Gastric Lesion

PubMed Central

Gwaram, Nura Suleiman; Al-Obaidi, Mazen M. Jamil; Soleimani, A. F.; Ali, Hapipah Mohd; Abdul Majid, Nazia

2013-01-01

Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP) 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg), the positive control (Tween 20 5% v/v, 5 mL/kg), and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg). After 1 h, all of the groups received ethanol 95% (5 mL/kg) but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg). The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E), immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats. PMID:24298554

A bioenergetics-kinetics coupled modeling study on subsurface microbial metabolism in a field biostimulation experiment

NASA Astrophysics Data System (ADS)

Jin, Q.; Zheng, Z.; Zhu, C.

2006-12-01

Microorganisms in nature conserve energy by catalyzing various geochemical reactions. To build a quantitative relationship between geochemical conditions and metabolic rates, we propose a bioenergetics-kinetics coupled modeling approach. This approach describes microbial community as a metabolic network, i.e., fermenting microbes degrade organic substrates while aerobic respirer, nitrate reducer, metal reducer, sulfate reducer, and methanogen consume the fermentation products. It quantifies the control of substrate availability and biological energy conservation on the metabolic rates using thermodynamically consistent rate laws. We applied this simulation approach to study the progress of microbial metabolism during a field biostimulation experiment conducted in Oak Ridge, Tennessee. In the experiment, ethanol was injected into a monitoring well and groundwater was sampled to monitor changes in the chemistry. With time, concentrations of ethanol and SO42- decreased while those of NH4+, Fe2+, and Mn2+ increased. The simulation results fitted well to the observation, indicating simultaneous ethanol degradation and terminal electron accepting processes. The rates of aerobic respiration and denitrification were mainly controlled by substrate concentrations while those of ethanol degradation, sulfate reduction, and methanogenesis were controlled dominantly by the energy availability. The simulation results suggested two different microbial growth statuses in the subsurface. For the functional groups with significant growth, variations with time in substrate concentrations demonstrated a typical S curve. For the groups without significant growth, initial decreases in substrate concentrations were linear with time. Injecting substrates followed by monitoring environmental chemistry therefore provides a convenient approach to characterize microbial growth in the subsurface where methods for direct observation are currently unavailable. This research was funded by the NABIR program, DOE, under grant No. DE-FG02-04ER63740 to CZ. We thank J. Istok, David Watson, and Philip Jardine for their help. The views and opinions of authors expressed herein do not necessarily state or reflect those of the DOE.

Chronic alcohol intake during adolescence, but not adulthood, promotes persistent deficits in risk-based decision making

PubMed Central

Schindler, Abigail G; Tsutsui, Kimberly T; Clark, Jeremy J

2014-01-01

Background Adolescent alcohol use is a major public health concern and is strongly correlated with the development of alcohol abuse problems in adulthood. Adolescence is characterized by maturation and remodeling of brain regions implicated in decision making and therefore may be uniquely vulnerable to environmental insults such as alcohol exposure. We have previously demonstrated that voluntary alcohol consumption in adolescence results in maladaptive risk-based decision making in adulthood. However, it is unclear whether this effect on risk-based decision making can be attributed to chronic alcohol use in general or to a selective effect of alcohol use during the adolescent period. Methods Ethanol was presented to adolescent (PND 30–49) and adult rats (PND 80–99) for 20 days, either 24h or 1h/day, in a gel matrix consisting of distilled water, gelatin, Polycose (10%), and ethanol (10%). The 24h time course of ethanol intake was measured and compared between adolescent and adult animals. Following 20 days of withdrawal from ethanol, we assessed risk-based decision making with a concurrent instrumental probability-discounting task. Blood ethanol concentrations (BECs) were taken from trunk blood and assessed using the Analox micro-stat GM7 in separate groups of animals at different time points. Results Unlike animals exposed to ethanol during adolescence, animals exposed to alcohol during adulthood did not display differences in risk preference compared to controls. Adolescent and adult rats displayed similar ethanol intake levels and patterns when given either 24h or 1h access/day. In addition, while both groups reached significant BEC levels we failed to find a difference between adult and adolescent animals. Conclusions Here we show that adolescent, but not adult, ethanol intake leads to a persistent increase in risk preference which cannot be attributed to differences in intake levels or BECs attained. Our findings support previous work implicating adolescence as a time period of heightened susceptibility to the long-term negative effects of alcohol exposure. PMID:24689661

Eye-Specific Gene Expression following Embryonic Ethanol Exposure in Zebrafish: Roles for Heat Shock Factor 1

PubMed Central

Kashyap, Bhavani; Pegorsch, Laurel; Frey, Ruth A.; Sun, Chi; Shelden, Eric A.; Stenkamp, Deborah L.

2014-01-01

The mechanisms through which ethanol exposure results in developmental defects remain unclear. We used the zebrafish model to elucidate eye-specific mechanisms that underlie ethanol-mediated microphthalmia (reduced eye size), through time-series microarray analysis of gene expression within eyes of embryos exposed to 1.5% ethanol. 62 genes were differentially expressed (DE) in ethanol-treated as compared to control eyes sampled during retinal neurogenesis (24-48 hours post-fertilization). The EDGE (extraction of differential gene expression) algorithm identified >3000 genes DE over developmental time in ethanol-exposed eyes as compared to controls. The DE lists included several genes indicating a mis-regulated cellular stress response due to ethanol exposure. Combined treatment with sub-threshold levels of ethanol and a morpholino targeting heat shock factor 1 mRNA resulted in microphthalmia, suggesting convergent molecular pathways. Thermal preconditioning partially prevented ethanol-mediated microphthalmia while maintaining Hsf-1 expression. These data suggest roles for reduced Hsf-1 in mediating microphthalmic effects of embryonic ethanol exposure. PMID:24355176

Comparison of enteral ethanol and benzodiazepines for alcohol withdrawal in neurocritical care patients.

PubMed

Gipson, Gregory; Tran, Kim; Hoang, Cuong; Treggiari, Miriam

2016-09-01

We designed a study to evaluate the use of benzodiazepines and ethanol in patients being assessed for alcohol withdrawal and compare outcomes between the two agents. This is a retrospective chart review of patients admitted to neurocritical care or neurosurgical services who were at risk for ethanol withdrawal between June 2011 and September 2015. Patients were divided into two groups based on the first medication administered for alcohol withdrawal management, either benzodiazepine (n=50) or enteral ethanol (n=50). The primary endpoint was the maximum change in Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA) score within the first 24hours. Secondary endpoints included maximum and minimum CIWA score in 5days, length of stay, and change in Glasgow Coma Scale. Study groups differed by mortality risk, level of coma at admission, and other clinical characteristics, with the ethanol group appearing less severely ill. There was no significant difference between the two groups in the maximum change in CIWA score at 24hours (-0.97, 95%CI: -3.21 to 1.27, p=0.39). Hospital and intensive care unit length of stay was 6.5 days and 1 day shorter for the ethanol group (p=0.03 and p=0.02, respectively). In summary, enteral ethanol was preferentially used in patients who are more likely to be capable of tolerating oral intake. We found that the change from baseline in CIWA score or other physiologic variables was not substantially different between the two agents. The overall utility of benzodiazepines and enteral ethanol remains unclear for this population and further study is needed to determine superiority. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aniracetam and DNQX affect the acquisition of rapid tolerance to ethanol in mice.

PubMed

Rial, Daniel; Takahashi, Reinaldo Naoto; Morato, Gina Struffaldi

2009-03-01

Several studies have emphasized the role of learning in the development of rapid tolerance and have shown that glutamate-mediated neurotransmission plays an important role in this phenomenon. Since the AMPA/kainate receptor system is directly involved in plasticity mechanisms, the influence of this receptor system on rapid tolerance induced by ethanol was studied using the rotarod. In the first experiment, mice were pretreated with aniracetam, an agonist of AMPA/kainate receptors, 30 min before ethanol (2.75 g/kg; IP) treatment, and tested on the rotarod. After 24 h, the groups were tested on the rotarod under ethanol treatment. Aniracetam facilitated the acquisition of rapid tolerance to ethanol. In the second experiment, mice received DNQX, a competitive antagonist of the AMPA receptor, 30 min before ethanol treatment (3 g/kg) and submitted to the rotarod. This dose of ethanol produced tolerance per se. Groups were tested under ethanol treatment (1.75 g/kg) after 24 h. DNQX blocked rapid tolerance to ethanol. Using a similar protocol, the third experiment showed that DNQX blocked the aniracetam-induced facilitation of rapid tolerance to ethanol. Our results show that aniracetam facilitates whereas DNQX blocks ethanol tolerance, suggesting that the non-NMDA receptors are involved in this phenomenon.

Inhibition of MMPs by alcohols

PubMed Central

Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Hoshika, Tomohiro; Uchiyama, Toshikazu; Tjäderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; Thompson, Jeremy M.; McCracken, Courtney E.; Looney, Stephen W.; Tay, Franklin R.; Pashley, David H.

2011-01-01

Objectives While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols. Methods The possible inhibitory activity of a series of alcohols was measured against soluble rhMMP-9 and insoluble matrix-bound endogenous MMPs of dentin in completely demineralized dentin. Increasing concentrations (0.17, 0.86, 1.71 and 4.28 moles/L) of a homologous series of alcohols (i.e. methanol, ethanol, propanols, butanols, pentanols, hexanols, the ethanol ester of methacrylic acid, heptanols and octanol) were compared to ethanediol, and propanediol by regression analysis to calculate the molar concentration required to inhibit MMPs by 50% (i.e. the IC50). Results Using two different MMP models, alcohols were shown to inhibit rhMMP-9 and the endogenous proteases of dentin matrix in a dose-dependent manner. The degree of MMP inhibition by alcohols increased with chain length up to 4 methylene groups. Based on the molar concentration required to inhibit rhMMP-9 fifty percent, 2-hydroxyethylmethacrylate (HEMA), 3-hexanol, 3-heptanol and 1-octanol gave the strongest inhibition. Significance The results indicate that alcohols with 4 methylene groups inhibit MMPs more effectively than methanol or ethanol. MMP inhibition was inversely related to the Hoy's solubility parameter for hydrogen bonding forces of the alcohols (i.e. to their hydrophilicity). PMID:21676453

Protection by Ethanolic Extract from Ulva lactuca L. against Acute Myocardial Infarction: Antioxidant and Antiapoptotic Activities.

PubMed

Widyaningsih, Wahyu; Pramono, Suwidjiyo; Zulaela; Sugiyanto; Widyarini, Sitarina

2017-12-01

Reactive oxygen species (ROS) play a major role in myocardial damage during acute myocardial infarction (AMI). This study aimed to determine the antioxidant and antiapoptotic activities of an ethanolic extract from Ulva lactuca L. (EEUL) against AMI. Thirty-six male Wistar rats were divided into six groups: one control group and five treatment groups. Treatment group II was given 85 mg/kg body weight (BW) of isoproterenol (ISO). Group III, IV and V were given ISO and EEUL at 250, 500 and 750 mg/kg BW, respectively. Group VI were given 10 mg/kg BW of ISO and melatonin. EEUL and melatonin were orally administered for 28 days. ISO was injected subcutaneously on day 29 and 30 to chemically induce AMI. On day 31, blood was collected for antioxidant assay and heart tissues were collected for histological examination. The activity of catalase (CAT), an endogenous antioxidant, in the EEUL-treatment groups was significantly increased compared to the ISO-treatment group ( P < 0.001). The EEUL-treatment groups showed significantly decreased expression of caspase-3 ( P < 0.001) and better myocardial tissue morphology. EEUL possibly protects against AMI because of its antioxidant and antiapoptotic properties.

Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

PubMed

Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

2011-08-01

Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults. Adolescents drank significantly more ethanol than adults on a gram per kilogram basis, with intake uninfluenced by prior ethanol exposure at both ages. Adolescents and adults may differ in their ability and/or propensity to adapt to chronic ethanol exposure, with adults, but not adolescents, developing chronic metabolic tolerance. However, this chronic exposure regimen was sufficient to disrupt baseline levels of social behavior at both ages. Taken together, these results suggest that, despite the age-related differences in tolerance development, adolescents are as susceptible as adults to consequences of chronic ethanol exposure, particularly in terms of disruptions in social behavior. Whether these effects would last into adulthood remains to be determined. Copyright © 2011 by the Research Society on Alcoholism.

Percutaneous ethanol injection for liver metastases.

PubMed

Riemsma, Robert P; Bala, Malgorzata M; Wolff, Robert; Kleijnen, Jos

2013-05-31

Primary liver tumours and liver metastases from colorectal carcinoma are the two most common malignant tumours to affect the liver. The liver is second only to the lymph nodes as the most common site for metastatic disease. More than half of the patients with metastatic liver disease will die from metastatic complications. Percutaneous ethanol injection (PEI) causes dehydration and necrosis of tumour cells accompanied by small vessel thrombosis, leading to tumour ischaemia and destruction. To study the beneficial and harmful effects of percutaneous ethanol injection compared with no intervention, other ablation methods, or systemic treatments in patients with liver metastases. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS, and CINAHL up to December 2012. We included all randomised clinical trials assessing the beneficial and harmful effects of percutaneous ethanol injection versus no intervention, other ablation methods, or systemic treatments in patients with liver metastases. We extracted the relevant information on participant characteristics, interventions, study outcome measures, and data on the outcome measures for our review, as well as information on the design and methodology of the studies. Quality assessment of the trials fulfilling the inclusion criteria and data extraction from the trials retrieved for final evaluation were done by one author and checked by a second author. One randomised clinical trial was included, comparing transcatheter arterial chemoembolisation (TACE) + percutaneous intratumour ethanol injection (PEI) versus TACE alone. Forty-eight patients with liver metastases were included; 25 received the intervention with PEI and 23 received TACE alone.Mortality data were not reported. The trial reported the survival data after one, two, and three years. In the TACE + PEI group, 92%, 80%, and 64% of the patients survived after 1, 2, and 3 years respectively; in the TACE group, 78.3%, 65.2%, and 47.8% of the patients survived after 1, 2, and 3 years respectively. The hazard ratio was 0.57 (95% CI 0.19 to 1.67). The local recurrence was 16% in the TACE + PEI group and 39.1% in the TACE group, resulting in a relative risk (RR) of 0.41 (95% CI 0.15 to 1.07). Forty-five tumours (66.2%) out of 68 tumours in total shrunk by at least 25% in the TACE + PEI group versus 31 tumours (48.4%) out of 64 tumours in total in the TACE group (RR 2.08; 95% CI 1.03 to 4.2). The authors reported some adverse events, but with very few details. On the basis of one small randomised trial, it can be concluded that addition of PEI to TACE, as compared with TACE alone, in patients with liver metastases seems to bring no clear benefit in terms of survival and local recurrence. The size of the tumour necrosis was larger in the combined treatment group. No intervention-related mortality or major complications were reported. More trials are needed.

Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive α1 GABAA receptors

PubMed Central

Werner, David F.; Swihart, Andrew R.; Ferguson, Carolyn; Lariviere, William R.; Harrison, Neil L.; Homanics, Gregg E.

2009-01-01

Background Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, γ-aminobutyric acid type A receptors (GABAA-Rs) have been extensively implicated in ethanol action. The α1 GABAA-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that α1-GABAA-Rs mediate in part these effects of ethanol. Methods Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin mice that have ethanol-insensitive α1 GABAA-Rs and wildtype controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex assays. Chronic tolerance was assessed on the loss of righting reflex, fixed speed rotarod, hypothermia, and radiant tail flick assays following ten consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess α1 protein levels. Results Compared to controls, knockin mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between wildtype and knockin mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in α1 protein levels, but knockins did not. Conclusions We conclude that α1-GABAA-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on α1-containing GABAA-Rs. PMID:19032579

Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

PubMed

Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

2018-02-15

Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Alpinia calcarata on glucose uptake in diabetic rats-an in vitro and in vivo model

PubMed Central

2014-01-01

Background Diabetes mellitus is a heterogeneous metabolic disorders characterized by abnormally high levels of blood glucose The main objective of the present work is to study the effect of Alpinia calcarata on glucose uptake in streptozotocin (STZ) induced diabetic rats. Methods The diabetes was induced by single dose of STZ (45 mg/kg) in citrate buffer, while the normal control group was given the vehicle (citrate buffer) only. After induction of diabetes, the diabetic animals were treated with ethanolic extract of Alpinia calcarata (200 mg/kg) and glibenclamide (2 mg/kg) for 30 days. Blood glucose estimation was performed every week of the study. At the end of study period, animals were sacrificed for biochemical studies. Results Streptozotocin induced diabetic rats shows the altered levels of various biochemical profiles. Those levels were brought back to near normal upon treatment with ethanolic extract of Alpinia calcarata and standard drug glibanclamide. No significant changes were observed on treatment with plant extract alone group indicated that there are no toxic substances present in Alpinia calcarata. The antidiabetic activity of plant extract was also further confirmed by histopathological studies. The ethanolic extract of Alpinia calcarata shows significant inhibition of alpha glucosidase activity and also enhancing the glucose uptake in rat hemidiaphragm. Conclusions In conclusion, the ethanolic extract of Alpinia calcarata ameliorates the condition associated with diabetes. PMID:24502532

Microbial diversity in sugarcane ethanol production in a Brazilian distillery using a culture-independent method.

PubMed

Costa, Ohana Yonara Assis; Souto, Betulia Morais; Tupinambá, Daiva Domenech; Bergmann, Jessica Carvalho; Kyaw, Cynthia Maria; Kruger, Ricardo Henrique; Barreto, Cristine Chaves; Quirino, Betania Ferraz

2015-01-01

Sugarcane ethanol production occurs in non-sterile conditions, and microbial contamination can decrease productivity. In this study, we assessed the microbial diversity of contaminants of ethanol production in an industrial facility in Brazil. Samples obtained at different stages were analyzed by pyrosequencing-based profiling of bacterial and archaeal 16S rRNA genes and the fungal internal transcribed spacer region. A total of 355 bacterial groups, 22 archaeal groups, and 203 fungal groups were identified, and community changes were related to temperature changes at certain stages. After fermentation, Lactobacillus and unclassified Lactobacillaceae accounted for nearly 100 % of the bacterial sequences. Predominant Fungi groups were "unclassified Fungi," Meyerozyma, and Candida. The predominant Archaea group was unclassified Thaumarchaeota. This is the first work to assess the diversity of Bacteria, and Archaea and Fungi associated with the industrial process of sugarcane-ethanol production using culture-independent techniques.

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses

PubMed Central

Pildervasser, João V. N.; Abrahao, Karina P.; Souza-Formigoni, Maria L. O.

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties. PMID:25152719

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses.

PubMed

Pildervasser, João V N; Abrahao, Karina P; Souza-Formigoni, Maria L O

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.

Moderate prenatal alcohol exposure alters behavior and neuroglial parameters in adolescent rats.

PubMed

Brolese, Giovana; Lunardi, Paula; Broetto, Núbia; Engelke, Douglas S; Lírio, Franciane; Batassini, Cristiane; Tramontina, Ana Carolina; Gonçalves, Carlos-Alberto

2014-08-01

Alcohol consumption by women during gestation has become increasingly common. Although it is widely accepted that exposure to high doses of ethanol has long-lasting detrimental effects on brain development, the case for moderate doses is underappreciated, and benchmark studies have demonstrated structural and behavioral defects associated with moderate prenatal alcohol exposure in humans and animal models. This study aimed to investigate the influence of in utero exposure to moderate levels of ethanol throughout pregnancy on learning/memory, anxiety parameters and neuroglial parameters in adolescent offspring. Female rats were exposed to an experimental protocol throughout gestation up to weaning. After mating, the dams were divided into three groups and treated with only water (control), non-alcoholic beer (vehicle) or 10% (vv) beer solution (moderate prenatal alcohol exposure - MPAE). Adolescent male offspring were subjected to the plus-maze discriminative avoidance task to evaluate learning/memory and anxiety-like behavior. Hippocampi were dissected and slices were obtained for immunoquantification of GFAP, NeuN, S100B and the NMDA receptor. The MPAE group clearly presented anxiolytic-like behavior, even though they had learned how to avoid the aversive arm. S100B protein was increased in the cerebrospinal fluid (CSF) in the group treated with alcohol, and alterations in GFAP expression were also shown. This study indicates that moderate ethanol doses administered during pregnancy could induce anxiolytic-like effects, suggesting an increase in risk-taking behavior in adolescent male offspring. Furthermore, the data show the possibility that glial cells are involved in the altered behavior present after prenatal ethanol treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

An assay for evoked locomotor behavior in Drosophila reveals a role for integrins in ethanol sensitivity and rapid ethanol tolerance.

PubMed

Bhandari, Poonam; Kendler, Kenneth S; Bettinger, Jill C; Davies, Andrew G; Grotewiel, Mike

2009-10-01

Ethanol induces similar behavioral responses in mammals and the fruit fly, Drosophila melanogaster. By coupling assays for ethanol-related behavior to the genetic tools available in flies, a number of genes have been identified that influence physiological responses to ethanol. To enhance the utility of the Drosophila model for investigating genes involved in ethanol-related behavior, we explored the value of an assay that measures the sedative effects of ethanol on negative geotaxis, an evoked locomotor response. We established eRING (ethanol Rapid Iterative Negative Geotaxis) as an assay for quantitating the sedative effects of ethanol on negative geotaxis (i.e., startle-induced climbing). We validated the assay by assessing acute sensitivity to ethanol and rapid ethanol tolerance in several different control strains and in flies with mutations known to disrupt these behaviors. We also used eRING in a candidate screen to identify mutants with altered ethanol-related behaviors. Negative geotaxis measured in eRING assays was dose-dependently impaired by ethanol exposure. Flies developed tolerance to the intoxicating effects of ethanol when tested during a second exposure. Ethanol sensitivity and rapid ethanol tolerance varied across 4 control strains, but internal ethanol concentrations were indistinguishable in the 4 strains during a first and second challenge with ethanol. Ethanol sensitivity and rapid ethanol tolerance, respectively, were altered in flies with mutations in amnesiac and hangover, genes known to influence these traits. Additionally, mutations in the beta integrin gene myospheroid and the alpha integrin gene scab increased the initial sensitivity to ethanol and enhanced the development of rapid ethanol tolerance without altering internal ethanol concentrations. The eRING assay is suitable for investigating genetic mechanisms that influence ethanol sensitivity and rapid ethanol tolerance. Ethanol sensitivity and rapid ethanol tolerance depend on the function of alpha and beta integrins in flies.

A novel controlled release ethanol emitter: preparation and effect on some postharvest quality parameters of Chinese bayberry during storage.

PubMed

Mu, Honglei; Gao, Haiyan; Chen, Hangjun; Fang, Xiangjun; Han, Qiang

2017-11-01

Reducing spoilage and prolonging the shelf-life of food materials are both critically important in the food industry. Among the many available preservatives, ethanol has been widely used for the storage of fruits and vegetables. Although a few ethanol emitters are available in the form of antimicrobial packaging, these ethanol emitters demonstrate high volatility, uncontrolled release and other disadvantages, and so the practical applications are limited. A novel ethanol gel with a controlled release rate was prepared by a gelatification reaction between ethanol and sodium stearate to overcome the disadvantage of conventional ethanol emitters. The hardness, adhesiveness and cohesiveness of developed ethanol gels increased, whereas the springiness decreased along with an increase in the sodium stearate concentration. The release rate of ethanol in the gels was controlled by the concentration of sodium stearate, in which a first-order release kinetic was observed. The release rate constant (k) of the gels with 12.5, 37.5, 62.5 g kg -1 of sodium stearate was 0.58 ± 0.029, 0.49 ± 0.035 and 0.41 ± 0.021 h -1 , respectively, at 25 °C. The application of the controlled release ethanol emitter with respect to the storage of Chinese bayberry fruit demonstrated its ability to reduce the decay rate, maintain firmness and inhibit increased malondialdehyde content at 4 °C. In terms of practical applications, an appropriate sodium stearate content can be selected in accordance with the storage period, aiming to achieve precise storage goals. Therefore, the ethanol emitter has potential application prospects as an active packaging for Chinese bayberry fruit, as well as for other perishable products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Effect of pH on ethanol-type acidogenic fermentation of fruit and vegetable waste.

PubMed

Wu, Yuanyuan; Wang, Cuiping; Zheng, Mingyue; Zuo, Jiane; Wu, Jing; Wang, Kaijun; Yang, Boqiong

2017-02-01

The aim of this study was to investigate the possibility and optimal controlling strategy for ethanol-type acidogenic fermentation of fruit and vegetable waste by mixed microbial cultures. Four continuous stirred tank reactors (CSTR) were operated at various pHs (4.0, 5.0, 5.5, and 6.0) with an organic loading rate of 13gVS/(Ld) and hydraulic retention time of 3d. Butyrate-type fermentation was observed at pH 5.0, 5.5, and 6.0. Conversely, at pH 4.0, ethanol-type fermentation was observed with a high mass concentration and proportion (of total fermentative products) of ethanol, which were 6.7g/L and 88.8%, respectively. However, the total concentration of ethanol-type fermentative products substantially decreased from days 22-25. The optimal pH of ethanol-type fermentative microorganisms was investigated by using batch experiments with pH controlled at 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, and 7.0 and results showed that the maximum ethanol concentration and relatively highest acidogenic rate were found at pH of 5.5. The pH in the long term CSTR was changed from 4.0 to 5.5 to improve ethanol-type fermentation and results showed that ethanol-type fermentation was improved temporarily, however, was followed by the reappearance of butyrate-type fermentation. In addition, ethanol-type fermentation recovered once more when pH was reverted to 4.0. Therefore, the results of this study suggest that a process of dynamic, sequenced pH control with the order pH 4.0, 5.5 and 4.0 might be a feasible controlling strategy for continuous and stable ethanol-type fermentation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Hibiscus rosa sinensis L (Malvaceae) on wound healing activity: a preclinical study in a Sprague Dawley rat.

PubMed

Shivananda Nayak, B; Sivachandra Raju, S; Orette, F A; Chalapathi Rao, A V

2007-06-01

Hibiscus rosa sinensis (H rosa sinensis), a plant product, has been used for the treatment of a variety of diseases as well as to promote wound healing. The wound-healing activity of the ethanol extract of H rosa sinensis flower was determined in rats, using excision, incision, and dead space wound models and is presented in this report. The animals were randomly divided into 2 groups of 6 each in all the models. Test group animals in each model were treated with the ethanol extract of H rosa sinensis orally by mixing in drinking water (120 mg kg(-1) day(-1)), and the control group animals were maintained with plain drinking water. Healing was assessed by the rate of wound contraction, period of epithelialization, tensile strength (skin breaking strength), granulation tissue weight, and hydroxyproline content. The antimicrobial activity of the flower extract against selected microorganisms that infect the wounds was also assessed. Animals treated with the extract exhibited an 86% reduction in the wound area compared with controls, who exhibited a 75% reduction. The extract-treated animals were found to epithelize their wounds significantly faster than controls (P < .002) and have shown significantly higher skin-breaking strength than controls (P < .002). The dry and wet weight of granulation tissue and hydroxyproline content were also increased significantly when compared with controls. The reported observations suggest H rosa sinensis aids wound healing in the rat model.

Microbiological and chemical profiles of elephant grass inoculated with and without Lactobacillus plantarum and Pediococcus acidilactici.

PubMed

Shah, Assar Ali; Xianjun, Yuan; Zhihao, Dong; Junfeng, Li; Sao, Tao

2018-03-01

The study was conducted to evaluate the microbiological and chemical profiles of elephant grass inoculated with and without different wild strains of lactic acid bacteria. Silage was prepared of four treatments and one control with three replicates as control (EKC, adding 2 ml/kg sterilizing water), Lactobacillus plantarum (USA commercial bacteria) (EKP), Lactobacillus plantarum (EKA), Pediococcus acidilactici (EKB), and Pediococcus acidilactici (SKD) isolated from King grass. Silage were prepared using polyethylene terephthalate bottles, and incubated at room temperature for different ensiling days. The pH and acetic acid (AA) were significantly (P < 0.05) reduced and lactic acid (LA), butyric acid (BA), and ethanol were significantly increased (P < 0.05) at 3, 5, 7, and 14 days in treatment groups as compared to control. Water-soluble carbohydrate (WSC) and NH 3 -N concentration was not affected at days 3, 5, and 7, but significantly (P < 0.05) reduced at 14 days in treatment groups as compared to control. The LA, BA, and ethanol were significantly (P < 0.05) increased and AA, WSC NH 3 -N, and yeast were significantly (P < 0.05) decreased at 30 days of ensiling in treatment groups as compared to control. It is recommended that the inoculation of LAB could improve the fermentation quality of elephant grass silage and further effort is needed to evaluate these effects on silage produced on farm scale and on animal production performance.

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

PubMed Central

Amato, Russell J.; Hulin, Mary W.; Winsauer, Peter J.

2012-01-01

Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectively for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol- and food-maintained responding, compared to control, while also decreasing blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared to food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, while not affecting ethanol-maintained responding compared to control. Low to intermediate doses of rauwolscine produced small, non-significant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence. PMID:22473025

Influence of fat/carbohydrate ratio on progression of fatty liver disease and on development of osteopenia in male rats fed alcohol via total enteral nutrition (TEN).

PubMed

Ronis, Martin J J; Mercer, Kelly; Suva, Larry J; Vantrease, Jamie; Ferguson, Matthew; Hogue, William R; Sharma, Neha; Cleves, Mario A; Blackburn, Michael L; Badger, Thomas M

2014-03-01

Alcohol abuse is associated with the development of fatty liver disease and also with significant osteopenia in both genders. In this study, we examined ethanol-induced pathology in response to diets with differing fat/carbohydrate ratios. Male Sprague-Dawley rats were fed intragastrically with isocaloric liquid diets. Dietary fat content was either 5% (high carbohydrate, HC) or 45% (high fat, HF), with or without ethanol (12-13 g/kg/day). After 14, 28, or 65 days, livers were harvested and analyzed. In addition, bone morphology was analyzed after 65 days. HC rats gained more weight and had larger fat pads than HF rats with or without ethanol. Steatosis developed in HC + ethanol (HC + EtOH) compared to HF + ethanol (HF + EtOH) rats, accompanied by increased fatty acid (FA) synthesis and increased nuclear carbohydrate response element binding protein (ChREBP) (p < 0.05), but in the absence of effects on hepatic silent mating type information regulation 2 homolog (SIRT-1) or nuclear sterol regulatory binding element protein (SREBP-1c). Ethanol reduced serum leptin (p < 0.05) but not adiponectin. Over time, HC rats developed fatty liver independent of ethanol. FA degradation was significantly elevated by ethanol in both HC and HF groups (p < 0.05). HF + EtOH rats had increased oxidative stress from 28 days, increased necrosis compared to HF controls and higher expression of cytochromes P450, CYP2E1, and CYP4A1 compared to HC + EtOH rats (p < 0.05). In contrast, HC + EtOH rats had no significant increase in oxidative stress until day 65 with no observed increase in necrosis. Unlike liver pathology, no dietary differences were observed on ethanol-induced osteopenia in HC compared to HF groups. These data demonstrate that interactions between diet composition and alcohol are complex, dependent on the length of exposure, and are an important influence in development of fatty liver injury. Importantly, it appears that diet composition does not affect alcohol-associated skeletal toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

PRENATAL ETHANOL EXPOSURE LEADS TO GREATER ETHANOL-INDUCED APPETITIVE REINFORCEMENT

PubMed Central

Pautassi, Ricardo M.; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.

2012-01-01

Prenatal ethanol significantly heightens later alcohol consumption, but the mechanisms that underlie this phenomenon are poorly understood. Little is known about the basis of this effect of prenatal ethanol on the sensitivity to ethanol’s reinforcing effects. One possibility is that prenatal ethanol exposure makes subjects more sensitive to the appetitive effects of ethanol or less sensitive to ethanol’s aversive consequences. The present study assessed ethanol-induced second-order conditioned place preference (CPP) and aversion and ethanol-induced conditioned taste aversion (CTA) in infant rats prenatally exposed to ethanol (2.0 g/kg) or vehicle (water) or left untreated. The involvement of the κ opioid receptor system in ethanol-induced CTA was also explored. When place conditioning occurred during the ascending limb of the blood-ethanol curve (Experiment 1), the pups exposed to ethanol in utero exhibited greater CPP than untreated controls, with a shift to the right of the dose-response curve. Conditioning during a later phase of intoxication (30–45 min post-administration; Experiment 2) resulted in place aversion in control pups exposed to vehicle during late gestation but not in pups that were exposed to ethanol in utero. Ethanol induced a reliable and similar CTA (Experiment 3) in the pups treated with vehicle or ethanol during gestation, and CTA was insensitive to κ antagonism. These results suggest that brief exposure to a moderate ethanol dose during late gestation promotes ethanol-mediated reinforcement and alters the expression of conditioned aversion by ethanol. This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance. PMID:22698870

Bacteriophage application restores ethanol fermentation characteristics disrupted by Lactobacillus fermentum

USDA-ARS?s Scientific Manuscript database

Background: Contamination of corn mash by lactic acid bacteria (LAB) reduces ethanol yields and the overall efficiency of the ethanol fermentation process, and the industry relies heavily on antibiotics for contamination control. There is a need to develop alternative methods for the control of cont...

Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by Ethanol.

PubMed

Bispo, Vanderson S; Dantas, Lucas S; Chaves, Adriano B; Pinto, Isabella F D; Silva, Railmara P DA; Otsuka, Felipe A M; Santos, Rodrigo B; Santos, Aline C; Trindade, Danielle J; Matos, Humberto R

2017-01-01

Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM), caffeic acid (1.1 µM), methyl caffeate (0.03 µM), quercetin (0.08 µM) and ferulic acid (0.02 µM) isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT) was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.

Ethanol consumption during pregnancy and lactation. Changes in the nutritional status of predominantly breastfeeding mothers.

PubMed

Villalpando, S; Flores-Huerta, S; Fajardo, A; Hernandez-Beltran, M J

1993-01-01

The purpose of this investigation was to study the effects of ethanol, consumed as a mild fermented beverage called "pulque", during pregnancy and lactation on the food intake and some anthropometric indices of body composition of a group of lactating mothers in a town in central Mexico. Thirty two mothers who drank pulque during pregnancy and lactation and 61 non-drinking women with comparable characteristics were evaluated anthropometrically, their dietary and ethanol intake recorded during a 6-month postpartum period. Energy [(8360 +/- 2997 vs. 7156 +/- 2177 J) and protein (52.7 +/- 20.9 vs. 44.6 +/- 16.1 g)] 24-h intake, height, weight, body mass index, arm muscle and fat areas were greater in drinking mothers than in controls. Average total ethanol consumption varied from 0.48 - 0.55 g-1 kg-1.d-1. Drinking mothers lost weight less frequently. Additional energy provided by pulque might explain such a difference. More precise information about the changes in their body composition and energy balance are in order for confirmation.

Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs.

PubMed

Asha, G S; Indira, M

2004-02-01

Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.

Exploring the role of curcumin containing ethanolic extract obtained from Curcuma longa (rhizomes) against retardation of wound healing process by aspirin.

PubMed

Pawar, Rajesh Singh; Toppo, Fedelic Ashish; Mandloi, Avinash Singh; Shaikh, Shabnam

2015-01-01

The aim of the study was to assess the curcumin containing ethanolic extract (EtOH) obtained from Curcuma longa (Cl) against retardation of wound healing by aspirin. Wound healing process was retarded by administering the dose of 150 mg/kg body weight of aspirin orally for 9 days to observe the effect of EtOH obtained from Cl using excision and incision wound model in rats. The various parameters such as % wound contraction, epithelialization period, hydroxyproline, tensile strength were observed at variant time intervals and histopathological study was also performed. Curcumin containing 5% and 10% ethanolic extract ointment have shown significant (P < 0.01) wound healing activity against an aspirin (administered 150 mg/kg body weight orally for 9 days) retarded wound healing process. Topical application of ointment showed significant (P < 0.01) difference as compared to the control group. Histopathological studies also showed healing of the epidermis, increased collagen, fibroblasts and blood vessels. Ethanolic extract of Cl ointment (EtOHCl) containing 10% curcumin displayed remarkable healing process against wound retardation by aspirin.

Control of ethanol withdrawal symptoms in mice by phenytoin.

PubMed

Sprague, G L; Craigmill, A L

1976-12-01

Mice were made physically dependent upon ethanol using either of two methods which involved ethanol vapor inhalation. Following the cessation of exposure to ethanol, the severity of handling-induced convulsions and changes in the response to an electric foot shock (startle reflex) were recorded. Animals given isotonic saline or propylene glycol:ethanol vehicle during withdrawal exhibited handling-induced convulsions, and ethanol (2.0-4.0 g/kg) or phenytoin (5-20 mg/kg) administration during withdrawal resulted in a reduction in the severity of these convulsions. A reduced startle reflex threshold was also evident during withdrawal in mice given isotonic saline or propylene glycol:ethanol vehicle. Ethanol (0.5-4.0 g/kg) or phenytoin (10-20 mg/kg) administration during withdrawal resulted in a significant elevation of the startle reflex threshold compared to control animals. The results are discussed as they relate to others obtained in experimental and clinical studies.

Circadian activity rhythms and voluntary ethanol intake in male and female ethanol-preferring rats: effects of long-term ethanol access.

PubMed

Rosenwasser, Alan M; McCulley, Walter D; Fecteau, Matthew

2014-11-01

Chronic alcohol (ethanol) intake alters fundamental properties of the circadian clock. While previous studies have reported significant alterations in free-running circadian period during chronic ethanol access, these effects are typically subtle and appear to require high levels of intake. In the present study we examined the effects of long-term voluntary ethanol intake on ethanol consumption and free-running circadian period in male and female, selectively bred ethanol-preferring P and HAD2 rats. In light of previous reports that intermittent access can result in escalated ethanol intake, an initial 2-week water-only baseline was followed by either continuous or intermittent ethanol access (i.e., alternating 15-day epochs of ethanol access and ethanol deprivation) in separate groups of rats. Thus, animals were exposed to either 135 days of continuous ethanol access or to five 15-day access periods alternating with four 15-day periods of ethanol deprivation. Animals were maintained individually in running-wheel cages under continuous darkness throughout the experiment to allow monitoring of free-running activity and drinking rhythms, and 10% (v/v) ethanol and plain water were available continuously via separate drinking tubes during ethanol access. While there were no initial sex differences in ethanol drinking, ethanol preference increased progressively in male P and HAD2 rats under both continuous and intermittent-access conditions, and eventually exceeded that seen in females. Free-running period shortened during the initial ethanol-access epoch in all groups, but the persistence of this effect showed complex dependence on sex, breeding line, and ethanol-access schedule. Finally, while females of both breeding lines displayed higher levels of locomotor activity than males, there was little evidence for modulation of activity level by ethanol access. These results are consistent with previous findings that chronic ethanol intake alters free-running circadian period, and show further that the development of chronobiological tolerance to ethanol may vary by sex and genotype. Copyright © 2014 Elsevier Inc. All rights reserved.

Antiulcerogenic activity of fractions and 3,15-dioxo-21alpha-hydroxy friedelane isolated from Maytenus robusta (Celastraceae).

PubMed

de Andrade, Sérgio Faloni; Comunello, Eros; Noldin, Vânia Floriani; Monache, Franco Delle; Cechinel Filho, Valdir; Niero, Rivaldo

2008-01-01

The hexane, chloroform, ethyl acetate and aqueous-soluble fractions from leaves of Maytenus robusta (Celastraceae) were evaluated for their protective actions against ethanol-induced gastric lesions in rats. The treatment with all fractions (150 mg/kg) and omeprazol (30 mg/kg) significantly reduced the lesion index, the total lesion area, and the percentage of lesion, in comparison with the control group (p<0.05). Since the ethyl acetate-soluble fraction was found to be most active in the pylorus ligated model, this fraction was further investigated and resulted in the isolation of triterpene 3,15-dioxo-21alpha-hydroxy friedelane. The triterpene was evaluated in the HCl/ethanol-induced ulcer model in mice. In this assay, both the groups treated with 3,15-dioxo-21alpha-hydroxy friedelane and omeprazol, at a dose of 30 mg/kg, presented a significant reduction in lesion index, total lesion area, and in the percentage of the lesion, when compared with the control group (p<0.05). The result suggests that the antiulcer effect observed in the extract and fractions may be attributed, at least in part, to this compound. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.

Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats.

PubMed

Toalston, Jamie E; Oster, Scott M; Kuc, Kelly A; Pommer, Tylene J; Murphy, James M; Lumeng, Lawrence; Bell, Richard L; McBride, William J; Rodd, Zachary A

2008-06-01

Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of ethanol and saccharin (SACC) deprivations on operant oral self-administration. Alcohol-preferring (P) rats were allowed to lever press concurrently self-administer ethanol (15% vol/vol) and SACC (0.0125% g/vol) for 8 weeks. Rats were then maintained on daily operant access (nondeprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of ethanol daily, or deprived of ethanol and given 2 ml of SACC daily. All groups were then given 2 weeks of daily operant access to ethanol and SACC, followed by an identical second deprivation period. P rats responded more for ethanol than SACC. All deprived groups increased responding on the ethanol lever, but not on the SACC lever. Daily consumption of 2 ml ethanol decreased the duration of the alcohol deprivation effect (ADE). Home cage access to 2 ml of SACC also decreased the ADE but to a lesser extent than access to ethanol. A second deprivation period further increased and prolonged the expression of an ADE. These results show ethanol is a more salient reinforcer than SACC. With concurrent access to ethanol and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both ethanol and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between ethanol and SACC in their CNS reinforcing effects.

Effects of the Cynanchum wilfordii Ethanol Extract on the Serum Lipid Profile in Hypercholesterolemic Rats

PubMed Central

Lee, Hye-Sung; Choi, Jun-Hyeok; Kim, Young-Eon; Kim, In-Ho; Kim, Byoung-Mok; Lee, Chang-Ho

2013-01-01

The purpose of this study was to investigate the effects of the ethanol extract of Cynanchum wilfordii (ECW) on the blood lipid profile of hypercholesterolemic rats. Thirty 7-week-old male Sprague-Dawley rats were allowed free access to either a normal diet (AIN-93 diet), or 1% high-cholesterol diet with or without 0.5% or 1% ECW for 5 weeks. After sacrifice, the rat serum lipid profile was analyzed. The diets containing ECW decreased body weight gains compared to the normal diet. Serum HDL-cholesterol levels of ECW-fed groups were significantly increased in the hypercholesterolemic groups and normal groups (P<0.05). When 1% ECW was fed to the normal group, total cholesterol level was increased. Moreover, treatment of ECW in hypercholesterolemic groups yielded a dose-dependent and highly significant decrease in the atherogenic index as compared to the control. These results suggest that intake of Cynanchum wilfordii may help reduce the risks of hypercholesterolemia by increasing blood HDL-cholesterol and lowering the atherogenic index. PMID:24471126

Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

PubMed Central

Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

2010-01-01

Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice did not change from baseline levels of intake. In contrast, HAP-2 females and LAP-2 mice of both sexes did not show changes in ethanol intake as a consequence of intermittent ethanol exposure. Conclusions Overall, these results indicate that the magnitude of ethanol withdrawal-related seizures is inversely related to inherited ethanol intake preference. Additionally, intermittent ethanol vapor exposure appears more likely to affect high-drinking mice (C57BL/6J and HAP-2) than low drinkers, even though these animals are less affected by ethanol withdrawal. PMID:21314693

Effect of intravenously-administered putative and potential antagonists of ethanol on sleep time in ethanol-narcotized mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatch, R.C.; Jernigan, A.D.

Groups of male CD-1 mice (n = 12/group) were injected intraperitoneally (IP) with 5 g ethanol/kg of body weight. After loss of righting reflex, they were given vehicle or one of 2-3 doses of reputed or potential antagonists of ethanol intravenously (IV). Sleep time was measured from loss to return of righting reflex. Mean sleep time (MST) was increased significantly by a large dose of dl-amphetamine and by 4-aminopyridine. Significant increases were also produced by small and large doses of aminophylline and by yohimbine. MST was not altered significantly by small and medium doses of dl-amphetamine, a medium dose ofmore » aminophylline, or by any doses of naloxone, thyrotropin-releasing hormone, propranolol, physostigmine, doxapram, or Ro 15-4513. When Ro 15-4513 was given IP 15 minutes before ethanol (n = 6/group), onset and duration of narcosis were not altered. None of the compounds tested was an effective IV antidote for deep ethanol narcosis because of drug side effects, toxicity, prolongation of MST, or insufficient shortening of MST. 36 references, 1 table.« less

Ethanol extract of Oenanthe javanica increases cell proliferation and neuroblast differentiation in the adolescent rat dentate gyrus

PubMed Central

Chen, Bai Hui; Park, Joon Ha; Cho, Jeong Hwi; Kim, In Hye; Shin, Bich Na; Ahn, Ji Hyeon; Hwang, Seok Joon; Yan, Bing Chun; Tae, Hyun Jin; Lee, Jae Chul; Bae, Eun Joo; Lee, Yun Lyul; Kim, Jong Dai; Won, Moo-Ho; Kang, Il Jun

2015-01-01

Oenanthe javanica is an aquatic perennial herb that belongs to the Oenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glutamate-induced neurotoxicity. However, few studies regarding effects of Oenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract of Oenanthe javanica on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 (an endogenous marker for cell proliferation) and doublecortin (a marker for neuroblast). Our results showed that Oenanthe javanica extract significantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was significantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not find that vascular endothelial growth factor expression was increased in the Oenanthe javanica extract-treated group compared with the control group. These results indicate that Oenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-derived neurotrophic factor immunoreactivity in the rat dentate gyrus. PMID:25883627

Randomized Double-Blind Placebo-Controlled Trial of Powdered Brassica rapa Ethanol Extract on Alteration of Body Composition and Plasma Lipid and Adipocytokine Profiles in Overweight Subjects

PubMed Central

Jeon, Seon-Min; Kim, Ji-Eun; Shin, Su-kyung; Kwon, Eun-young; Jung, Un Ju; Baek, Nam-In; Lee, Kyung-Tae; Jeong, Tae-Sook; Chung, Hae-Gon

2013-01-01

Abstract We evaluated the effects of Brassica rapa ethanol extract (BREE) on body composition and plasma lipid profiles through a randomized, double-blind, and placebo-controlled trial in overweight subjects. Fifty-eight overweight participants (age 20–50 years, body mass index23.0–24.9) were randomly assigned to two groups and served BREE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. Body compositions, nutrients intake, plasma lipids, adipocytokines, and hepatotoxicity biomarkers were assessed in all subjects at baseline and after 10 weeks of supplementation. The plasma total cholesterol (total-C) concentration was significantly increased after 10 weeks compared to the baseline in both groups. However, BREE supplementation significantly increased the high-density lipoprotein cholesterol (HDL-C) concentration and significantly reduced the total-C/HDL-C ratio, free fatty acid, and adipsin levels after 10 weeks. No significant differences were observed in body compositions, fasting blood glucose, plasma adipocytokines except adipsin, and aspartate aminotransferase and alanine aminotransferase activities between before and after trial within groups as well as between the two groups. The supplementation of BREE partially improves plasma lipid metabolism in overweight subjects without adverse effects. PMID:23342969

GABAA Receptor Regulation of Voluntary Ethanol Drinking Requires PKCε

PubMed Central

Besheer, Joyce; Lepoutre, Veronique; Mole, Beth; Hodge, Clyde W.

2010-01-01

Protein kinase C (PKC) regulates a variety of neural functions, including ion channel activity, neurotransmitter release, receptor desensitization and differentiation. We have shown previously that mice lacking the ε-isoform of PKC (PKCε) self-administer 75% less ethanol and exhibit supersensitivity to acute ethanol and allosteric positive modulators of GABAA receptors when compared with wild-type controls. The purpose of the present study was to examine involvement of PKCε in GABAA receptor regulation of voluntary ethanol drinking. To address this question, PKCε null-mutant and wild-type control mice were allowed to drink ethanol (10% v/v) vs. water on a two-bottle continuous access protocol. The effects of diazepam (nonselective GABAA BZ positive modulator), zolpidem (GABAA α1 agonist), L-655,708 (BZ-sensitive GABAA α5 inverse agonist), and flumazenil (BZ antagonist) were then tested on ethanol drinking. Ethanol intake (grams/kg/day) by wild-type mice decreased significantly after diazepam or zolpidem but increased after L-655,708 administration. Flumazenil antagonized diazepam-induced reductions in ethanol drinking in wild-type mice. However, ethanol intake by PKCε null mice was not altered by any of the GABAergic compounds even though effects were seen on water drinking in these mice. Increased acute sensitivity to ethanol and diazepam, which was previously reported, was confirmed in PKCε null mice. Thus, results of the present study show that PKCε null mice do not respond to doses of GABAA BZ receptor ligands that regulate ethanol drinking by wild-type control mice. This suggests that PKCε may be required for GABAA receptor regulation of chronic ethanol drinking. PMID:16881070

Chronic moderate alcohol consumption relieves high-fat high-cholesterol diet-induced liver fibrosis in a rat model.

PubMed

Sun, Furong; Zhuang, Zhenjie; Zhang, Dai; Chen, Yushuai; Liu, Shu; Gao, Nan; Shi, Junping; Wang, Bingyuan

2018-05-30

Nonalcoholic fatty liver disease is a worldwide health issue and chronic alcohol consumption may have different effects on this disease. This study explored the role of chronic moderate alcohol consumption on high-fat high-cholesterol (HFHC) diet-induced liver fibrosis in a rodent model. Male Sprague-Dawley rats were divided into five groups: standard chow group, standard chow plus Er Guo Tou (EGT, a Chinese spirits made from fermented cereals) group, HFHC group, HFHC plus EGT group, and HFHC plus pure ethanol group. Rats were fed standard chow or HFHC chow for 12 weeks. EGT or pure ethanol was administrated at a daily dose of 4 g/kg body weight via intra-gastric gavage from the week four. At the end of week 12, hematoxylin and eosin staining, Sirius red and immunohistochemistry of liver sections were examined. The hepatic expression of F4/80, TNF-α, IL-1β, IL-6, CXCL1, CXCL2, α-SMA, Collagen, TGF-β, MMP2, MMP9, and TIMP1 was calculated. Both moderate EGT and pure ethanol did not increase plasma endotoxin in the portal vein comparing with the FHFC group. EGT and pure ethanol did not improve hepatic inflammation, but ameliorated liver fibrosis in histology. Moderate EGT and pure ethanol ameliorated HFHC diet-induced activation of Kupffer cells and hepatic stellate cells. In conclusion, chronic moderate EGT and pure ethanol could ameliorate HFHC diet-induced liver fibrosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cytogenetic analysis of oral mucosa cells, induced by chlorhexidine, essential oils in ethanolic solution and triclosan mouthwashes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ros-Llor, Irene; Lopez-Jornet, Pia, E-mail: majornet@um.es

Objectives: The aim of this study was to evaluate DNA damage and cytokinetic defects, proliferative potential and cell death caused by the frequent use of mouthrinses containing chlorhexidine, triclosan and essential oils in ethanolic solution, compared to a placebo mouthwash. Study design: This double-blind, prospective, randomized clinical trial included 80 Caucasian patients. Subjects were divided into four groups: Group I used a mouthrinse, Triclosan; Group II used physiological saline; Group III used chlorhexidine; Group IV a mouthrinse with essential oils in ethanolic solution. All subjects used the mouthrinses for two weeks (15 ml, twice a day, rinsing for 30 s).more » Two cell samples per subject were collected, before and after mouthrinse use (on day 0 and day 15). Samples were processed as follows: cell collection from cheeks with a cytobrush; cell centrifuge; slide preparation, fixation and staining; and fluorescent microscope analysis. 2000 exfoliated cells were screened for nuclear abnormalities, particularly the presence of micronuclei by means of cytome assay. Results: No significant differences between study times (before and after use of mouthwash) were identified for any of the variables studied (p>0.05). Differences between mouthrinse groups were also compared but no significant differences were found (p>0.05). Conclusions: This study did not observe any genotoxic effect resulting from mouthrinse use. - Highlights: • Mouthrinses are used widely, mainly for their capacity to control dental plaque. • No genotoxic effects from the mouthrinses triclosan, chlorhexidine essential oils solution. • The buccal cytome assay is a sensitive, non-invasive, and low cost technique.« less

A history of alternative reinforcement reduces stimulus generalization of ethanol-seeking in a rat recovery model.

PubMed

Ginsburg, Brett C; Lamb, R J

2013-04-01

Longer periods of recovery reduce the likelihood of relapse, which may be due to a reduced ability of various stimuli to occasion alcohol or drug seeking. However, this hypothesis remains largely uninvestigated. Here we assessed the ability of intermediate stimuli to occasion responding for ethanol in rats trained to discriminate an 8 kHz tone signaling a food fixed-ratio (FR) of 5 and an ethanol FR5, from a 16 kHz tone signaling a food FR150 and ethanol FR5. In the presence of the 8 kHz tone responding for food predominates, and in the presence of the 16 kHz tone, responding for ethanol predominates. In the context of alternation between these conditions, varying the tone from 8 to 16 kHz produces a graded increase in ethanol (versus food) responding, consistent with a stimulus generalization function. A recent history of responding under food-predominant choice conditions, either during the test session or in the four sessions that precede it shifts the generalization function downwards. Extending this history to nine sessions shifts the curve further downwards. The stimulus generalization function was similar in a separate group, trained with different relative ratios for food and ethanol, but with similar behavioral allocation under each discriminative stimulus. Finally, withholding access to food and ethanol for 4 or 16 sessions did not affect the stimulus generalization gradient. These results suggest that longer histories of reinforced alternative behavior might reduce the likelihood of relapse by decreasing the control exerted over alcohol- or drug-seeking by stimuli similar to those that previously occasioned alcohol- or drug-seeking. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis.

PubMed

Chacko, Balu K; Srivastava, Anup; Johnson, Michelle S; Benavides, Gloria A; Chang, Mi Jung; Ye, Yaozu; Jhala, Nirag; Murphy, Michael P; Kalyanaraman, Balaraman; Darley-Usmar, Victor M

2011-07-01

Chronic alcohol-induced liver disease results in inflammation, steatosis, and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone (MitoQ) (5 and 25 mg/kg/day for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α), and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis, and induction of cytochrome P450 2E1 (CYP2E1). MitoQ had a minor effect on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities; however, it did decrease hepatic steatosis in ethanol-consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocked the increase in HIF1α in all ethanol-fed groups, which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol-associated mitochondrial reactive oxygen species (ROS) and several downstream effects of ROS/RNS (reactive nitrogen species) production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependent HIF1α stabilization. Copyright © 2011 American Association for the Study of Liver Diseases.

Trait anxiety and ethanol: anxiolysis in high-anxiety mice and no relation to intake behavior in an addiction model.

PubMed

Correia, Diego; Ribeiro, Andrea Frozino; Brunialti Godard, Ana Lúcia; Boerngen-Lacerda, Roseli

2009-08-01

Anxiety has been proposed to play a role in the development of alcohol addiction, but the exact mechanisms by which this occurs remain unclear. The present study aimed to verify the relationship between basal anxiety levels, the anxiolytic-like effect of ethanol, and ethanol intake in mice exposed to an addiction model. In one experiment Swiss mice were characterized as high-anxiety (HA), medium-anxiety (MA), or non-anxiety (NA) in the elevated plus maze and then received saline or ethanol 2 g/kg acutely and chronically and were again exposed to the same test. NA mice decreased while MA mice maintained anxiety indices over the test days, regardless of treatment. HA ethanol-treated mice showed an anxiolytic-like effect, both acutely and chronically, while the saline-treated ones maintained their basal anxiety levels. In another experiment HA and MA mice were exposed to an addiction model based on a 3-bottle free-choice paradigm (ethanol 5% and 10%, and water) consisting of four phases: acquisition (10 weeks), withdrawal (W, 2 weeks), reexposure (2 weeks), and quinine-adulteration (2 weeks). HA and MA control mice had access only to water. Mice were characterized as addicted, heavy-drinker and light-drinker [Fachin-Scheit DJ, Ribeiro AF, Pigatto G, Goeldner FO, Boerngen-Lacerda R. Development of a mouse model of ethanol addiction: naltrexone efficacy in reducing consumption but not craving. J Neural Transm 2006;113:1305-21.]. No difference was observed between HA and MA mice in their preference for and intake of ethanol. No correlation was observed between ethanol intake, during any phase, and anxiety indices measured in the basal tests and during the W phase. The differences in anxiety indices between HA and MA groups persisted in the test performed during ethanol withdrawal, suggesting a "trait" anxiety profile. The data suggest that despite the fact that high anxiety trait levels are important for the anxiolytic-like effects of ethanol, they are not a determining factor for high ethanol intake, at least not under these experimental conditions.

Toxicological outcomes in rats exposed to inhaled ethanol during gestation.

PubMed

Beasley, Tracey E; Evansky, Paul A; Martin, Sheppard A; McDaniel, Katherine L; Moser, Virginia C; Luebke, Robert W; Norwood, Joel; Rogers, John M; Copeland, Carey B; Bushnell, Philip J

2014-01-01

Recent legislation has encouraged replacing petroleum-based fuels with renewable alternatives including ethanol, which is typically blended with gasoline in the United States at concentrations up to 10%, with allowances for concentrations up to 85% for some vehicles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol, and the lack of information about its toxicity by inhalation prompted the present work on its potential developmental effects in a rat model. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or ethanol vapor at concentrations of 5000, 10,000, or 21,000 ppm, which resulted in estimated peak blood ethanol concentrations (BECs) of 2.3, 6.7, and 192 mg/dL, respectively. No overt toxicity in the dams was observed. Ethanol did not affect litter size or weight, or postnatal weight gain in the pups. Motor activity was normal in offspring through postnatal day (PND) 29. On PND 62, the 5000 and 21,000 ppm groups were more active than controls. On PND 29 and 62, offspring were tested with a functional observational battery, which revealed small changes in the neuromuscular and sensorimotor domains that were not systematically related to dose. Cell-mediated and humoral immunity were not affected by ethanol exposure in 6-week-old offspring. Systolic blood pressure was increased by 10,000 ppm ethanol in males at PND 90 but not at PND 180. No differences in lipoprotein profile, liver function, or kidney function were observed. In summary, prenatal exposure to inhaled ethanol caused some mild changes in physiological and behavioral development in offspring that were not clearly related to inhaled concentration or BEC, and did not produce detectable changes in immune function. This low toxicity of inhaled ethanol may result from the slow rise in BEC by the inhalation route. Published by Elsevier Inc.

Modulation of Ethanol Withdrawal–Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/γ-Aminobutyric Acid Ligands

PubMed Central

Knapp, Darin J.; Overstreet, David H.; Breese, George R.

2010-01-01

Background Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal–associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of γ-aminobutyric acid–modulating drugs on social interaction behavior—an established model of anxiety—in rats exposed to repeated cycles of ethanol treatment and withdrawal. Methods Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl–6, 7–dymerhoxy–4–ethyl–beta–carboline–3–carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Results Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Conclusions Single-dose administration of drugs that enhance or diminish activity at benzodiazepine–γ-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals. PMID:15834220

Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/gamma-aminobutyric acid ligands.

PubMed

Knapp, Darin J; Overstreet, David H; Breese, George R

2005-04-01

Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal-associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of gamma-aminobutyric acid-modulating drugs on social interaction behavior-an established model of anxiety-in rats exposed to repeated cycles of ethanol treatment and withdrawal. Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl-6, 7-dymerhoxy-4-ethyl-beta-carboline-3-carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals.

Does mitomycin C cause toxicity in the cornea after photorefractive keratectomy? A comparative wound-healing study in a refractive surgery animal model.

PubMed

Blanco-Mezquita, Tomas; Espandar, Ladan; Torres, Rodrigo; Alvarez-Barcia, Angel; Cantalapiedra-Rodriguez, Roberto; Martinez-Garcia, Carmen; Merayo-Lloves, Jesus

2014-11-01

In this study, we investigated the wound-healing process after photorefractive keratectomy with mitomycin C (MMC) in hen corneas. In addition, we evaluated the synergistic effect of ethanol and MMC. Forty-eight adult hens were divided into 3 groups: A: ethanol-assisted debridement plus MMC; B: mechanical debridement plus MMC; and C: mechanical debridement (MMC-untreated control). Photorefractive keratectomy was performed, and the animals were followed up for up to 60 days. Epithelial healing was measured with fluorescein. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end-labeling assay and proliferation was measured by BrdU incorporation. Both myofibroblast differentiation and collagen deposition were evaluated by immunofluorescence and histology. Epithelial wound closure was similar in all 3 groups (P > 0.05). Significant reduction in haze was observed in groups A and B compared with C (P < 0.01), but there was no difference between groups A and B (P > 0.05). Furthermore, there was no difference in the number of apoptotic cells between groups. Proliferation was delayed in both groups A and B compared with C (P < 0.01), but groups A and B did not differ significantly (P > 0.05). Myofibroblasts, cellular density, and collagen deposition were lower in both groups A and B compared with C (P < 0.01), but they were not significantly different from each other (P > 0.05). Topical application of MMC in hen corneas reproduces the wound healing observed in humans by reducing haze, keratocyte proliferation, myofibroblast differentiation, and new collagen deposition. Synergistic cytotoxic effects of ethanol and MMC were not observed.

Delaying microbial proliferation in freshly peeled shallots by active packaging incorporating ethanol vapour-controlled release sachets and low storage temperature.

PubMed

Utto, Weerawate; Preutikul, Rittirong; Malila, Patcharee; Noomhorm, Athapol; Bronlund, John E

2018-03-01

This research was conducted to investigate effects of ethanol vapour released in active packaging and storage temperatures on the quality of freshly peeled shallots. The package tested was a solid polypropylene tray incorporating an ethanol vapour-controlled release sachet. The sachet was made of an aluminium foil film on one side and either low-density polyethylene or nylon/polyethylene on the other. Individual sachets contained silica gel adsorbent as the carrier pre-loaded with ethanol. One sachet was placed in each tray containing the peeled shallots and the tray was heat sealed with the low-density polyethylene film lid. Packages were stored at either 10 or 25 ℃ for 10 d. Trays containing only peeled shallots were designated as controls. High storage temperature stimulated quality changes in the shallots. Although ethanol vapour accumulated in the active package headspace, the extent to which ethanol concentrations increased within the shallots was not significantly different from that in the control packages. Microbial proliferation in terms of yeast and mould counts could be delayed through a combination of 10 ℃ and ethanol vapour released from the low-density polyethylene sachet. The ethanol vapour accumulated in the packages did not have a significant effect on mass loss, firmness, and colour changes in the peeled shallots, or on the concentrations of oxygen and carbon dioxide in the packages.

Antioxidant mechanism is involved in the gastroprotective effects of ozonized sunflower oil in ethanol-induced ulcers in rats.

PubMed

Zamora Rodríguez, Zullyt B; González Alvarez, Ricardo; Guanche, Dailén; Merino, Nelson; Hernández Rosales, Frank; Menéndez Cepero, Silvia; Alonso González, Yaima; Schulz, Siegfried

2007-01-01

This research was performed in order to determine the potential protective effects of ozonized sunflower oil (OSO) in the injury of rat gastric mucosa induced by absolute ethanol and as well as to elucidate the role of reactive oxygen species (ROS), lipid peroxidation, and some important constituents of antioxidant defense such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in these effects. OSO was administered to rats intragastrically by a cannula and it was applied during four days to animals. The doses of OSO administered daily to each group of rats were 4, 12, and 24 mg/kg, respectively, and one hour after the last treatment, absolute ethanol (1 mL/200 mg body weight) was administered. Our results showed that gastric ulcer index was significantly reduced in rats pretreated with OSO as compared with ethanol-treated controls. However, in rats pretreated with OSO, no significant reduction of TBARS content in gastric mucosa was found as compared to those rats treated with ethanol alone. In contrast, SOD and GSH-Px activities were significantly increased in gastric mucosa of OSO-pretreated rats with respect to those treated with ethanol alone. In summary, our results demonstrate that OSO pretreatment exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore, these results provide evidence that these protective effects of OSO are mediated at least partially by stimulation of some important antioxidant enzymes such as SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury induced by them.

Antioxidant Mechanism is Involved in the Gastroprotective Effects of Ozonized Sunflower Oil in Ethanol-Induced Ulcers in Rats

PubMed Central

Rodríguez, Zullyt B. Zamora; Álvarez, Ricardo González; Guanche, Dailén; Merino, Nelson; Rosales, Frank Hernández; Cepero, Silvia Menéndez; González, Yaima Alonso; Schulz, Siegfried

2007-01-01

This research was performed in order to determine the potential protective effects of ozonized sunflower oil (OSO) in the injury of rat gastric mucosa induced by absolute ethanol and as well as to elucidate the role of reactive oxygen species (ROS), lipid peroxidation, and some important constituents of antioxidant defense such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in these effects. OSO was administered to rats intragastrically by a cannula and it was applied during four days to animals. The doses of OSO administered daily to each group of rats were 4, 12, and 24 mg/kg, respectively, and one hour after the last treatment, absolute ethanol (1 mL/200 mg body weight) was administered. Our results showed that gastric ulcer index was significantly reduced in rats pretreated with OSO as compared with ethanol-treated controls. However, in rats pretreated with OSO, no significant reduction of TBARS content in gastric mucosa was found as compared to those rats treated with ethanol alone. In contrast, SOD and GSH-Px activities were significantly increased in gastric mucosa of OSO-pretreated rats with respect to those treated with ethanol alone. In summary, our results demonstrate that OSO pretreatment exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore, these results provide evidence that these protective effects of OSO are mediated at least partially by stimulation of some important antioxidant enzymes such as SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury induced by them. PMID:17497036

Cardioprotective effects of red wine and vodka in a model of endothelial dysfunction

PubMed Central

Lassaletta, Antonio D; Chu, Louis M; Elmadhun, Nassrene Y; Burgess, Thomas A; Feng, Jun; Robich, Michael P; Sellke, Frank W

2012-01-01

Background Moderate alcohol consumption is largely believed to be cardioprotective, while red wine is hypothesized to offer benefit in part due to the pro-angiogenic and antioxidant properties of polyphenols. We investigated the cardiovascular effects of both red wine and vodka in a swine model of endothelial dysfunction. Methods Twenty-seven male Yorkshire swine fed a high-fat/cholesterol diet were divided into three groups and received either no alcohol (Control), red wine, or vodka. After seven weeks, myocardial perfusion was measured, and ventricular tissue was analyzed for microvascular reactivity, and immunohistochemical studies. Results There were no differences in myocardial perfusion, in arteriolar or capillary density, or in VEGF expression among groups. Total protein oxidation as well as expression of superoxide dismutase-1 and -2 (SOD1, SOD2) and NADPH-oxidase (NOX2) was decreased in both treatment groups compared to controls. Endothelium-dependent microvessel relaxation, however, was significantly improved only in the red wine-supplemented group. Conclusions Supplementation with both red wine and vodka decreased oxidative stress by several measures, implicating the effects of ethanol in reducing oxidative stress in the myocardium. However, it was only in the red wine-supplemented group that an improvement in microvessel function was observed. This suggests that a component of red wine, independent of ethanol, possibly a polyphenol such as resveratrol, may confer cardioprotection by normalizing endothelial dysfunction induced by an atherogenic diet. PMID:22748601

Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.

PubMed

Rompala, Gregory R; Finegersh, Andrey; Homanics, Gregg E

2016-06-01

A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol-drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice

PubMed Central

Rompala, Gregory R.; Finegersh, Andrey; Homanics, Gregg E.

2016-01-01

A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. PMID:27286933

Protective effects of Lactococcus chungangensis CAU 28 on alcohol-metabolizing enzyme activity in rats.

PubMed

Konkit, Maytiya; Kim, Kiyoung; Kim, Jong-Hwa; Kim, Wonyong

2018-04-19

In this study, we investigated the beneficial effects of Lactococcus chungangensis CAU 28, a bacterial strain of nondairy origin, on alcohol metabolism in rats treated with ethanol, focusing on alcohol elimination and prevention of damage and comparing the effects with those observed for Lactococcus lactis ssp. lactis ATCC 19435. Male Sprague-Dawley rats were orally administered 20% ethanol and 3 substrates (freeze-dried cells, cream cheese, and yogurt) containing Lc. chungangensis CAU 28 or Lc. lactis ssp. lactis ATCC 19435, which were provided 1 h before or 1 h after ethanol ingestion. Blood samples were collected from the tail veins of the rats at 1, 3, 6, 12, and 24 h after ingestion of ethanol, Lc. chungangensis CAU 28 substrate, or Lc. lactis ssp. lactis ATCC 19435 substrate. Alcohol and acetaldehyde concentrations in the Lc. chungangensis CAU 28 substrate-treated rats were significantly reduced in a time-dependent manner compared with those in the Lc. lactis ssp. lactis ATCC 19435 substrate-treated rats. Among the experimental groups, treatment with cream cheese before ingestion of 20% ethanol was found to be the most effective method for reducing both alcohol and acetaldehyde levels in the blood. Alanine aminotransferase and aspartate aminotransferase activities in the Lc. chungangensis CAU 28 substrate-treated rats were significantly lower than those in the positive controls. Moreover, in the Lc. chungangensis CAU 28 cream cheese-treated group, rats showed a reduction of liver enzymes by up to 60%, with good effectiveness observed for both pre- and post-ethanol ingestion. These results suggested that intake of lactic acid bacteria, particularly in Lc. chungangensis CAU 28-supplemented dairy products, may reduce blood alcohol and acetaldehyde concentrations, thereby mitigating acute alcohol-induced hepatotoxicity by altering alcohol-metabolizing enzyme activities. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells.

PubMed

Jung, Yunu; Park, Jinbong; Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-10-20

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH.

Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells

PubMed Central

Kim, Hye-Lin; Youn, Dong-Hyun; Kang, JongWook; Lim, Seona; Jeong, Mi-Young; Sethi, Gautam; Park, Sung-Joo; Ahn, Kwang Seok; Um, Jae-Young

2017-01-01

Benign prostatic hyperplasia (BPH) is a common disease in the male population, especially in elderly men. Vanillic acid (VA), a dihydroxybenzoic derivative used as a flavoring agent, is reported to have an anti-inflammatory effect. However, there are no reports of its effects on BPH to date. BPH was induced with a pre-4-week treatment of daily subcutaneous injections of testosterone propionate (TP), and the normal control group received injections of ethanol with corn oil instead. Six weeks of further injections were done with (a) ethanol with corn oil, (b) TP only, (c) TP + finasteride, and (d) TP + VA. Finasteride was used as a positive control group. VA had protective effects on the TP-induced BPH. In the VA treatment group, the prostate weight was reduced, and the histological changes including the epithelial thickness and lumen area were restored like in the normal control group. Furthermore, in the VA treatment group, two proliferation related factors, high molecular weight cytokeratin 34βE12 and α smooth muscle actin, were significantly down-regulated compared to the TP-induced BPH group. The expressions of dihydrotestosterone and 5α-reductase, the most crucial factors in BPH development, were suppressed by VA treatment. Expressions of the androgen receptor, estrogen receptor α and steroid receptor coactivator 1 were also significantly inhibited by VA compared to the TP-induced BPH group. In addition, we established an in vitro model for BPH by treating a normal human prostatic epithelial cell line RWPE-1 with TP. VA successfully inhibited proliferation and BPH-related factors in a concentration-dependent manner in this newly established model. These results suggest a new and potential pharmaceutical therapy of VA in the treatment of BPH. PMID:29152074

Effect of additional etching and ethanol-wet bonding on the dentin bond strength of one-step self-etch adhesives

PubMed Central

Ahn, Joonghee; Jung, Kyoung-Hwa; Son, Sung-Ae; Hur, Bock; Kwon, Yong-Hoon

2015-01-01

Objectives This study examined the effects of additional acid etching on the dentin bond strength of one-step self-etch adhesives with different compositions and pH. The effect of ethanol wetting on etched dentin bond strength of self-etch adhesives was also evaluated. Materials and Methods Forty-two human permanent molars were classified into 21 groups according to the adhesive types (Clearfil SE Bond [SE, control]; G-aenial Bond [GB]; Xeno V [XV]; Beauti Bond [BB]; Adper Easy Bond [AE]; Single Bond Universal [SU]; All Bond Universal [AU]), and the dentin conditioning methods. Composite resins were placed on the dentin surfaces, and the teeth were sectioned. The microtensile bond strength was measured, and the failure mode of the fractured specimens was examined. The data were analyzed statistically using two-way ANOVA and Duncan's post hoc test. Results In GB, XV and SE (pH ≤ 2), the bond strength was decreased significantly when the dentin was etched (p < 0.05). In BB, AE and SU (pH 2.4 - 2.7), additional etching did not affect the bond strength (p > 0.05). In AU (pH = 3.2), additional etching increased the bond strength significantly (p < 0.05). When adhesives were applied to the acid etched dentin with ethanol-wet bonding, the bond strength was significantly higher than that of the no ethanol-wet bonding groups, and the incidence of cohesive failure was increased. Conclusions The effect of additional acid etching on the dentin bond strength was influenced by the pH of one-step self-etch adhesives. Ethanol wetting on etched dentin could create a stronger bonding performance of one-step self-etch adhesives for acid etched dentin. PMID:25671215

Influence of the use of statin on the stability of erythrocyte membranes in multiple sclerosis.

PubMed

de Freitas, Mariana Vaini; de Oliveira, Marcela Ramos; dos Santos, Diogo Fernandes; de Cássia Mascarenhas Netto, Rita; Fenelon, Sheila Bernardino; Penha-Silva, Nilson

2010-02-01

Multiple sclerosis (MS) probably occurs by oxidative, inflammatory and autoimmune mechanisms. This study investigated the influence of statin on the stability of erythrocyte membranes in MS patients. The population was composed of one group with simvastatin therapy (20 mg/day), another group without statin therapy and a healthy control group. The stability of erythrocytes was evaluated by the half-transition points, H(50) and D(50), obtained from the curves of hemolysis induced by hypotonic shock and ethanol action, respectively. Erythrocytes of MS patients were less stable against lysis by both chaotropes. This behavior may be merely a consequence of the lifestyle of MS patients or it may be intrinsically associated with the conjunct of factors responsible for the development of the disease. The use of statin by MS patients was associated with lower levels of LDL and total cholesterol, as expected, and with higher stability of erythrocytes against ethanol compared to the values of untreated MS patients.

Ethanol adaptation induces direct protection and cross-protection against freezing stress in Salmonella enterica serovar Enteritidis.

PubMed

He, S; Zhou, X; Shi, C; Shi, X

2016-03-01

Salmonella enterica serovar Enteritidis (Salm. Enteritidis) encounters mild ethanol stress during its life cycle. However, adaptation to a stressful condition may affect bacterial resistance to subsequent stresses. Hence, this work was undertaken to investigate the influences of ethanol adaptation on stress tolerance of Salm. Enteritidis. Salmonella Enteritidis was subjected to different ethanol adaptation treatments (2·5-10% ethanol for 1 h). Cellular morphology and tolerance to subsequent environmental stresses (15% ethanol, -20°C, 4°C, 50°C and 10% NaCl) were evaluated. It was found that 10% was the maximum ethanol concentration that allowed growth of the target bacteria. Ethanol adaptation did not cause cell-surface damage in Salm. Enteritidis as revealed by membrane permeability measurements and electron micrograph analysis. Salmonella Enteritidis adapted with 2·5-10% ethanol displayed an enhanced resistance to a 15%-ethanol challenge compared with an unchallenged control. The maximum ethanol resistance was observed when ethanol concentration used for ethanol adaptation was increased to 5·0%. Additionally, pre-adaptation to 5·0% ethanol cross-protected Salm. Enteritidis against -20°C, but not against 4°C, 50°C or 10% NaCl. Ethanol adaptation provided Salm. Enteritidis direct protection from a high level ethanol challenge and cross-protection from freezing, but not other stresses tested (low temperature, high salinity or high temperature). The results are valuable in developing adequate and efficient control measures for Salm. Enteritidis in foods. © 2016 The Society for Applied Microbiology.

Paradox effects of binge drinking on response inhibition processes depending on mental workload.

PubMed

Stock, Ann-Kathrin; Riegler, Lea; Chmielewski, Witold X; Beste, Christian

2016-06-01

Binge drinking is an increasing problem in Western societies, but we are still only beginning to unravel the effects of binge drinking on a cognitive level. While common sense suggests that all cognitive functions are compromised during high-dose ethanol intoxication, several studies suggest that the effects might instead be rather specific. Moreover, some results suggest that the degrees of automaticity and complexity of cognitive operations during response control modulate effects of binge drinking. However, this has not been tested in detail. In the current study, we therefore parametrically modulate cognitive/"mental" workload during response inhibition and examine the effects of high-dose ethanol intoxication (~1.1 ‰) in n = 18 male participants. The results suggest that detrimental effects of high-dose ethanol intoxication strongly depend on the complexity of processes involved in response inhibition. The results revealed strong effects (η (2) = .495) and are in line with findings showing that even high doses of ethanol have very specific effects on a cognitive level. Opposed to common sense, more complex cognitive operations seem to be less affected by a high-dose ethanol intoxication. Complementing this, high-dose ethanol intoxication is increasingly detrimental for action control, as stronger automated response tendencies are in charge and need to be controlled. Binge-like ethanol intoxication may take a heavier toll on cognitive control processes than on automated responses/response tendencies. Therefore, ethanol effects are more pronounced in supposedly "easier" control conditions because those facilitate the formation of automated response tendencies.

Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice

PubMed Central

Ho, Ada Man-Choi; Qiu, Yanyan; Jia, Yun-Fang; Aguiar, Felipe S.; Hinton, David J.; Karpyak, Victor M.; Weinshilboum, Richard M.; Choi, Doo-Sup

2016-01-01

Background Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). Since negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergist effect of FDA approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol consumption in stress-induced depressed mice. Methods Forty singly-housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3 weeks, depressive- and anxiety-like behaviors and ethanol consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/day), escitalopram (5 mg/kg; twice/day), or their combination (n = 9–11/drug group/stress group). Two-bottle choice limited access drinking of 15% ethanol and tap water was performed 3 hours into dark phase for 2 hours immediately after the dark phase daily injection. Ethanol drinking was monitored for another 7 days without drug administration. Results Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression- and anxiety-like behaviors compared to their non-stressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher ethanol consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in ethanol consumption in non-stressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the post-drug administration period. Conclusions The combination of acamprosate and escitalopram suppressed ethanol intake in both non-stressed and stressed mice, hence this combination is potentially helpful for AUD individuals with or without comorbid depression to reduce alcohol use. PMID:27184383

Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats

PubMed Central

Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

2017-01-01

Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as “Medang payung” by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of A. sesquipedalis was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of A. sesquipedalis extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with A. sesquipedalis extract, which showed its prominent gastroprotective potential in rats’ stomach against ethanol-induced ulcer. PMID:28496305

Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats.

PubMed

Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

2017-01-01

Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as "Medang payung" by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of A. sesquipedalis was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of A. sesquipedalis extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with A. sesquipedalis extract, which showed its prominent gastroprotective potential in rats' stomach against ethanol-induced ulcer.

Event-Related Potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats

PubMed Central

Ehlers, Cindy L.; Desikan, Anita; Wills, Derek N.

2014-01-01

Background The present study explored the hypothesis that adolescent ethanol exposure may cause long lasting changes in ethanol sensitivity by exploring the age-related effects of acute alcohol on intoxication and on event-related potential (ERP) responses to acoustic stimuli in ethanol naïve adolescent and adult male Wistar rats and in adult rats that were exposed to chronic ethanol/control conditions during adolescence. Methods Ethanol naïve adolescent (postnatal day 32 (PD32)) and adult male rats (PD99) were included in the first study. In a second study, rats were exposed to 5 weeks of ethanol vapor (Blood ethanol concentrations @ 175 mg%) or air from PD24 to PD59 and allowed to mature until PD90. In both studies rats were implanted with cortical recording electrodes, and the effects of acute ethanol (0.0, 1.5, and 3.0 g/kg) on behavioral and ERP responses were assessed. Results Adolescents were found to have higher amplitude and longer latency P3a and P3b components at baseline as compared to adult rats, and ethanol was found to produce a robust dose-dependent increase in the latency of the P3a and P3b components of the auditory ERP recorded in cortical sites in both adolescents and adults. However, ethanol produced significantly larger delays in P3a and P3b latencies in adults as compared to adolescents. Acute ethanol administration was also found to produce a robust dose dependent increase in the latency of the P3a and P3b components in adult animals exposed to ethanol vapor as adolescents and air exposed controls; however, larger acute ethanol-induced increases in P3a and P3b latencies were seen in controls as compared to adolescent vapor exposed rats. Conclusions Adolescent rats have a less intense P3 latency response to acute ethanol administration when compared to adult rats. Exposure to chronic ethanol during adolescence can cause “retention” of the adolescent phenotype of reduced P3 latency sensitivity to ethanol. PMID:24483322

Modulation of ethanol toxicity by Asian ginseng (Panax ginseng) in Japanese ricefish (Oryzias latipes) embryogenesis.

PubMed

Haron, M H; Avula, B; Khan, I A; Mathur, S K; Dasmahapatra, A K

2013-04-01

Alcohol consumption by women during pregnancy often induces fetal alcohol spectrum disorder (FASD) in children who have serious central nervous system (CNS), cardiovascular, and craniofacial defects. Prevention of FASD, other than women abstaining from alcohol drinking during pregnancy, is not known. A limitation of the use of synthetic anti-alcoholic drugs during pregnancy led us to investigate herbal products. In particular, many plants including Asian ginseng (Panax ginseng) have therapeutic potential for the treatment of alcoholism. We used Japanese ricefish (medaka) (Oryzias latipes), an animal model of FASD, for identifying herbal medicines that can attenuate ethanol toxicity. Fertilized eggs in standard laboratory conditions were exposed to ginseng (PG) root extract (0-2 mg/mL) either 0-2 (group A) or 1-3 (group B) day post fertilization (dpf) followed by maintenance in a clean hatching solution. The calculated IC50 as determined 10 dpf in A and B groups were 355.3±1.12 and 679.7±1.6 μg/mL, respectively. Simultaneous exposure of embryos in sub-lethal concentrations of PG (50-200 μg/mL) and ethanol (300 mM) for 48 h disrupted vessel circulation and enhanced mortality. However, PG (100 μg/mL) may partially protect trabecular cartilage (TC) deformities in the neurocranium in B group embryos induced by ethanol (300 mM). To understand the mechanism, embryonic ethanol concentration was measured at 2 dpf and adh5, adh8, aldh2, aldh9a, catalase, GST, and GR mRNAs were analyzed at 6 dpf. It was observed that although ethanol is able to reduce adh8 and GST mRNA contents, the simultaneous addition of PG was unable to alter ethanol level as well as mRNA contents in these embryos. Therefore, antagonistic effects of PG on ethanol toxicity are mediated by a mechanism which is different from those regulating ethanol metabolism and oxidative stress. Published by Elsevier Inc.

Effect of acute beer ingestion on the liver: studies in female mice.

PubMed

Kanuri, Giridhar; Wagnerberger, Sabine; Landmann, Marianne; Prigl, Eva; Hellerbrand, Claus; Bischoff, Stephan C; Bergheim, Ina

2015-04-01

The aim of the present study was to assess whether the effects of acute consumption of stout or pilsner beer on the liver differ from those of plain ethanol in a mouse model. Seven-week-old female C57BL/6J mice received either ethanol, stout or pilsner beer (ethanol content: 6 g/kg body weight) or isocaloric maltodextrin solution. Plasma alanine transaminase, markers of steatosis, lipogenesis, activation of the toll-like receptor-4 signaling cascade as well as lipid peroxidation and fibrogenesis in the liver were measured 12 h after acute ethanol or beer intake. Acute alcohol ingestion caused a marked ~11-fold increase in hepatic triglyceride accumulation in comparison to controls, whereas in mice exposed to stout and pilsner beer, hepatic triglyceride levels were increased only by ~6.5- and ~4-fold, respectively. mRNA expression of sterol regulatory element-binding protein 1c and fatty acid synthase in the liver did not differ between alcohol and beer groups. In contrast, expression of myeloid differentiation primary response gene 88, inducible nitric oxide synthases, but also the concentrations of 4-hydroxynonenal protein adducts, nuclear factor κB and plasminogen activator inhibitor-1 were induced in livers of ethanol treated mice but not in those exposed to the two beers. Taken together, our results suggest that acute ingestion of beer and herein especially of pilsner beer is less harmful to the liver than the ingestion of plain ethanol.

Gastroprotective effect of Cymbopogon citratus infusion on acute ethanol-induced gastric lesions in rats.

PubMed

Sagradas, Joana; Costa, Gustavo; Figueirinha, Artur; Castel-Branco, Maria Margarida; Silvério Cabrita, António Manuel; Figueiredo, Isabel Vitória; Batista, Maria Teresa

2015-09-15

Treatment of gastric ulcers with medicinal plants is quite common in traditional medicine worldwide. Cymbopogon citratus (DC) Stapf. leaves infusion has been used in folk medicine of many tropical and subtropical regions to treat gastric disturbances. The aim of this study was to assess the potential gastroprotective activity of an essential oil-free infusion from C. citratus leaves in acute gastric lesions induced by ethanol in rat. The study was performed on adult male Wistar rats (234.0±22.7g) fasted for 24h but with free access to water. The extract was given orally before (prevention) or after (treatment) intragastric administration of absolute ethanol. Effects of dose (28 or 56mg/kg of body weight) and time of contact of the extract with gastric mucosa (1 or 2h) were also assessed. Animals were sacrificed, being the stomachs removed and the lesions were assessed by macroscopic observation and histopathology. C. citratus extract, given orally before or after ethanol, significantly (P<0.01) reduced gastric mucosal injury compared with control group (vehicle+ethanol). The effect does not appear to be dose-dependent. Results also suggested that the extract is more effective when the time of contact with gastric mucosa increases. The results of this assay confirm the gastroprotective activity of C. citratus extract on experimental gastric lesions induced by ethanol, contributing for the pharmacological validation of its traditional use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bursaphelenchus xylophilus is killed by homologues of 2-(1-undecyloxy)-1-ethanol

NASA Astrophysics Data System (ADS)

Kim, Junheon; Lee, Sang-Myeong; Park, Chung Gyoo

2016-07-01

2-(1-Undecyloxy)-1-ethanol, monochamol, is a male-produced aggregation pheromone of the Monochamus species, which are efficient vectors of the pine wood nematode (PWN), Bursaphelenchus xylophilus, which cause devastating damage to pines worldwide. The nematicidal activity of synthetic monochamol and its homologues (ROEtOH: R = C7-C13) were investigated to find potential alternatives to the currently used PWN control agents abamectin and emamectin. Compounds with C7-C13 chain length alkyl groups exhibited 100% nematicidal activity at a concentration of 1000 mg/L. At a concentration of 100 mg/L, 2-(1-nonyloxy)-1-ethanol (C9OEtOH), 2-(1-decyloxy)-1-ethanol (C10OEtOH), 2-(1-undecyloxy)-1-ethanol (C11OEtOH), and 2-(1-dodecyloxy)-1-ethanol (C12OEtOH) showed 100% nematicidal activity, but the others showed weaker activities. C11OEtOH showed similar nematicidal activity to abamectin in terms of LD90 values, which were 13.30 and 12.53 mg/L, respectively. However, C9OEtOH, C10OEtOH, and C12OEtOH (LC90 values: 53.63, 38.18, and 46.68 mg/L, respectively) were less effective than C11OEtOH and abamectin. These results indicate that monochamol could be an effective alternative agent against PWN. The relationship of insecticidal and nematicidal activity to different carbon chain lengths in compounds is discussed.

Dynamic behaviors and transport properties of ethanol molecules in transmembrane cyclic peptide nanotubes.

PubMed

Li, Rui; Fan, Jianfen; Li, Hui; Yan, Xiliang; Yu, Yi

2015-07-07

Classical molecular dynamics simulations have been performed to investigate the dynamic behaviors and transport properties of ethanol molecules in transmembrane cyclic peptide nanotubes (CPNTs) with various radii, i.e., 8×(WL¯)n=3,4,5/POPE. The results show that ethanol molecules spontaneously fill the octa- and deca-CPNTs, but not the hexa-CPNT. In the octa-CPNT, ethanol molecules are trapped at individual gaps with their carbon skeletons perpendicular to the tube axis and hydroxyl groups towards the tube wall, forming a broken single-file chain. As the channel radius increases, ethanol molecules inside the deca-CPNT tend to form a tubular layer and the hydroxyl groups mainly stretch towards the tube axis. Computations of diffusion coefficients indicate that ethanol molecules in the octa-CPNT nearly lost their diffusion abilities, while those in the deca-CPNT diffuse as 4.5 times as in a (8, 8) carbon nanotube with a similar tube diameter. The osmotic and diffusion permeabilities (pf and pd, respectively) of the octa- and deca-CPNTs transporting ethanol were deduced for the first time. The distributions of the gauche and trans conformers of ethanol molecules in two CPNTs are quite similar, both with approximately 57% gauche conformers. The non-bonded interactions of channel ethanol with a CPNT wall and surrounding ethanol were explored. The potential of mean force elucidates the mechanism underlying the transporting characteristics of channel ethanol in a transmembrane CPNT.

Ethanol extract of Peperomia pellucida (Piperaceae) promotes fracture healing by an anabolic effect on osteoblasts.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Tewari, Deepshikha; Dimo, Theophile; Kamtchouing, Pierre; Maurya, Rakesh; Chattopadhyay, Naibedya

2013-06-21

The whole plant or some part of Peperomia pellucida (L.) HBK is used in some parts of Cameroon as a treatment for fracture healing. To evaluate the effect of ethanolic extracts of Peperomia pellucida (L.), a Cameroonian medicinal plant on bone regeneration following bone and marrow injury, and determine the mode of action. Ethanol extract of Peperomia pellucida was administered at 100 and 200mg/kg doses orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of calcein labeling at the drill hole site was performed to evaluate bone regeneration. 3-D microarchitecture of drill hole site was analyzed by micorocomputed tomography. Osteogenic effects of the extract were evaluated by assessing mineralized nodule formation of bone marrow stromal cells and expression of osteogenic genes (mRNA level of type-1 collagen, bone morphogenetic protein-2 and osteocalcin genes) in the femur. Ethanol extract from Peperomia Pellucida (L.) dose-dependently induced bone regeneration at the fracture site. At 200mg/kg dose, the extract significantly increased mineral deposition compared to controls. The extract also improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. In addition, the extract increased the formation of mineralized nodules from the bone marrow stromal cells. Furthermore, the extract induced the expression of osteogenic genes in the femur including type 1 collagen, osteocalcin and BMP-2, compared to control. Ethanolic extract of P. pellucid (L.) accelerates fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying its traditional use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Co-production of acetone and ethanol with molar ratio control enables production of improved gasoline or jet fuel blends.

PubMed

Baer, Zachary C; Bormann, Sebastian; Sreekumar, Sanil; Grippo, Adam; Toste, F Dean; Blanch, Harvey W; Clark, Douglas S

2016-10-01

The fermentation of simple sugars to ethanol has been the most successful biofuel process to displace fossil fuel consumption worldwide thus far. However, the physical properties of ethanol and automotive components limit its application in most cases to 10-15 vol% blends with conventional gasoline. Fermentative co-production of ethanol and acetone coupled with a catalytic alkylation reaction could enable the production of gasoline blendstocks enriched in higher-chain oxygenates. Here we demonstrate a synthetic pathway for the production of acetone through the mevalonate precursor hydroxymethylglutaryl-CoA. Expression of this pathway in various strains of Escherichia coli resulted in the co-production of acetone and ethanol. Metabolic engineering and control of the environmental conditions for microbial growth resulted in controllable acetone and ethanol production with ethanol:acetone molar ratios ranging from 0.7:1 to 10.0:1. Specifically, use of gluconic acid as a substrate increased production of acetone and balanced the redox state of the system, predictively reducing the molar ethanol:acetone ratio. Increases in ethanol production and the molar ethanol:acetone ratio were achieved by co-expression of the aldehyde/alcohol dehydrogenase (AdhE) from E. coli MG1655 and by co-expression of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (AdhB) from Z. mobilis. Controlling the fermentation aeration rate and pH in a bioreactor raised the acetone titer to 5.1 g L(-1) , similar to that obtained with wild-type Clostridium acetobutylicum. Optimizing the metabolic pathway, the selection of host strain, and the physiological conditions employed for host growth together improved acetone titers over 35-fold (0.14-5.1 g/L). Finally, chemical catalysis was used to upgrade the co-produced ethanol and acetone at both low and high molar ratios to higher-chain oxygenates for gasoline and jet fuel applications. Biotechnol. Bioeng. 2016;113: 2079-2087. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ethanol does not delay muscle recovery but decreases testosterone/cortisol ratio.

PubMed

Haugvad, Anders; Haugvad, Lars; Hamarsland, Håvard; Paulsen, Gøran

2014-11-01

This study investigated the effects of ethanol consumption on recovery from traditional resistance exercise in recreationally trained individuals. Nine recreationally trained volunteers (eight males and one female, 26 ± 4 yr, 81 ± 4 kg) conducted four resistance exercise sessions and consumed a low (0.6 (females) and 0.7 (males) g · kg(-1) body mass) or a high dose (1.2 or 1.4 g · kg(-1) body mass) of ethanol 1-2.5 h after exercise on two occasions. The first session was for familiarization with the tests and exercises and was performed without ethanol consumption. As a control trial, alcohol-free drinks were consumed after the exercise session. The sequence of trials, with low and high ethanol doses and alcohol-free drinks (control), was randomized. Maximal voluntary contractions (MVC) (knee extension), electrically stimulated contractions (knee extension), squat jumps, and hand grip strength were assessed 10-15 min and 12 and 24 h after the ethanol/placebo drinks. In addition to a baseline sample, blood was collected 1, 12, and 24 h after the ethanol/placebo drinks. The exercise session comprised 4 × 8 repetition maximum of squats, leg presses, and knee extensions. MVC were reduced by 13%-15% immediately after the exercise sessions (P < 0.01). MVC, electrically stimulated force, and squat jump performance were recovered 24 h after ethanol drinks. MVC was not fully recovered at 24 h in the control trial. Compared with those in the control, cortisol increased and the free testosterone/cortisol ratio were reduced after the high ethanol dose (P < 0.01). Neither a low nor a high dose of ethanol adversely affected recovery of muscle function after resistance exercise in recreationally strength-trained individuals. However, the increased cortisol levels and reduced testosterone/cortisol ratio after the high ethanol dose could translate into long-term negative effects.

Comparative effects of dietary corn oil, safflower oil, fish oil and palm oil on metabolism of ethanol and carnitine in the rat.

PubMed

Sachan, Dileep S; Yatim, Ayub M; Daily, James W

2002-06-01

This study was launched to determine comparative effects of corn oil (CO), safflower oil (SO), fish oil (FO) and palm oil (PO) on carnitine status and ethanol metabolism in rats. Twenty-four male Sprague-Dawley rats (300 g bw) were randomly divided into four groups (n = 6) and fed a semisynthetic diets containing fat as oils listed above. Blood and 24 hour urine samples were collected before and after dietary treatment and acute ethanol administration. Samples were analyzed for blood-ethanol concentration (BEC) and carnitine species. The diets containing FO and PO retarded ethanol metabolism compared to the diets containing CO and SO. The effect of these dietary fats on carnitine species in plasma and urine was varied before and after dietary treatment and following a single oral ethanol dose. The liver carnitine content was higher in the PO group after dietary and ethanol treatment. It is concluded that attenuation of ethanol clearance was related to unique fatty acid makeup of the oils that in part may be attributed to the composite ratio of saturated to unsaturated fatty acids in the oils.

The impacts of deacetylation prior to dilute acid pretreatment on the bioethanol process

PubMed Central

2012-01-01

Background Dilute acid pretreatment is a promising pretreatment technology for the biochemical production of ethanol from lignocellulosic biomass. During dilute acid pretreatment, xylan depolymerizes to form soluble xylose monomers and oligomers. Because the xylan found in nature is highly acetylated, the formation of xylose monomers requires two steps: 1) cleavage of the xylosidic bonds, and 2) cleavage of covalently bonded acetyl ester groups. Results In this study, we show that the latter may be the rate limiting step for xylose monomer formation. Furthermore, acetyl groups are also found to be a cause of biomass recalcitrance and hydrolyzate toxicity. While the removal of acetyl groups from native corn stover by alkaline de-esterification prior to pretreatment improves overall process yields, the exact impact is highly dependent on the corn stover variety in use. Xylose monomer yields in pretreatment generally increases by greater than 10%. Compared to pretreated corn stover controls, the deacetylated corn stover feedstock is approximately 20% more digestible after pretreatment. Finally, by lowering hydrolyzate toxicity, xylose utilization and ethanol yields are further improved during fermentation by roughly 10% and 7%, respectively. In this study, several varieties of corn stover lots were investigated to test the robustness of the deacetylation-pretreatment-saccharification-fermentation process. Conclusions Deacetylation shows significant improvement on glucose and xylose yields during pretreatment and enzymatic hydrolysis, but it also reduces hydrolyzate toxicity during fermentation, thereby improving ethanol yields and titer. The magnitude of effect is dependent on the selected corn stover variety, with several varieties achieving improvements of greater than 10% xylose yield in pretreatment, 20% glucose yield in low solids enzymatic hydrolysis and 7% overall ethanol yield. PMID:22369467

Acute, food-induced moderate elevation of plasma uric acid protects against hyperoxia-induced oxidative stress and increase in arterial stiffness in healthy humans.

PubMed

Vukovic, Jonatan; Modun, Darko; Budimir, Danijela; Sutlovic, Davorka; Salamunic, Ilza; Zaja, Ivan; Boban, Mladen

2009-11-01

We examined the effects of acute, food-induced moderate increase of plasma uric acid (UA) on arterial stiffness and markers of oxidative damage in plasma in healthy males exposed to 100% normobaric oxygen. Acute elevation of plasma UA was induced by consumption of red wine, combination of ethanol and glycerol, or fructose. By using these beverages we were able to separate the effects of UA, wine polyphenols and ethanol. Water was used as a control beverage. Ten males randomly consumed test beverages in a cross-over design over the period of 4 weeks, one beverage per week. They breathed 100% O(2) between 60(th) and 90(th)min of the 4-h study protocol. Pulse wave augmentation index (AIx) at brachial and radial arteries, plasma antioxidant capacity (AOC), thiobarbituric acid-reactive substances (TBARS), lipid hydroperoxides (LOOH) assessed by xylenol orange method, UA and blood ethanol concentrations were determined before and 60, 90, 120, 150 and 240 min after beverage consumption. Consumption of the beverages did not affect the AIx, TBARS or LOOH values during 60 min before exposure to hyperoxia, while AOC and plasma UA increased except in the water group. Significant increase of AIx, plasma TBARS and LOOH, which occurred during 30 min of hyperoxia in the water group, was largely prevented in the groups that consumed red wine, glycerol+ethanol or fructose. In contrast to chronic hyperuricemia, generally considered as a risk factor for cardiovascular diseases and metabolic syndrome, acute increase of UA acts protectively against hyperoxia-induced oxidative stress and related increase of arterial stiffness in large peripheral arteries.

Mechanistic studies on the transformation of ethanol into ethene over Fe-ZSM-5 zeolite.

PubMed

Maihom, Thana; Khongpracha, Pipat; Sirijaraensre, Jakkapan; Limtrakul, Jumras

2013-01-14

Ethanol, through the utilization of bioethanol as a chemical resource, has received considerable industrial attention as it provides an alternative route to produce more valuable hydrocarbons. Using a density functional theory approach incorporating the M06-L functional, which includes dispersion interactions, a large 34T nanocluster model of Fe-ZSM-5 zeolite in which T is a Si or Al atom is employed to examine both the stepwise and concerted mechanisms of the transformation of ethanol into ethene. For the stepwise mechanism, ethanol dehydration commences from the first hydrogen abstraction of the ethanol OH group to form the ethoxide-hydroxide intermediate with a low activation energy of 17.7 kcal mol(-1). Consequently, the ethoxide-hydroxide intermediate is decomposed into ethene through hydrogen abstraction from the ethoxide methyl carbon to either the OH group of hydroxide or the oxygen of the ethoxide group with high activation energies of 64.8 and 63.5 kcal mol(-1), respectively. For the concerted mechanism, ethanol transformation into the ethene product occurs in a single step without intermediate formation, with an activation energy of 32.9 kcal mol(-1). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-inflammatory activities of ethanolic extract of Carica papaya leaves.

PubMed

Owoyele, Bamidele V; Adebukola, Olubori M; Funmilayo, Adeoye A; Soladoye, Ayodele O

2008-08-01

The anti-inflammatory activity of an ethanolic extract of Carica papaya leaves was investigated in rats using carrageenan induced paw oedema, cotton pellet granuloma and formaldehyde induced arthritis models. Experimental animals received 25-200 mg/Kg (orally) of the extracts or saline (control group) and the reference group received 5 mg/ Kg of indomethacin. The ulcerogenic activity of the extract was also investigated. The results show that the extracts significantly (p <0.05) reduced paw oedema in the carrageenan test. Likewise the extract produced significant reduction in the amount of granuloma formed from 0.58 +/-0.07 to 0.22 +/-0.03 g. In the formaldehyde arthritis model, the extracts significantly reduced the persistent oedema from the 4th day to the 10th day of the investigation. The extracts also produced slight mucosal irritation at high doses. The study establishes the anti-inflammatory activity of Carica papaya leaves.

Ethanol teratogenesis in the C57BL/6J, DBA/2J, and A/J inbred mouse strains.

PubMed

Boehm, S L; Lundahl, K R; Caldwell, J; Gilliam, D M

1997-01-01

Research has shown variations in susceptibility to alcohol-related birth defects in humans. Genetic differences are one reason for this variability. This study compared three inbred mouse strains to determine whether they differ in their susceptibilities to ethanol teratogenesis because previous studies have generated conflicting data. Pregnant C57BL/6J (B6), DBA/2J (D2), and A/J (A) dams were intubated intragastrically with either an acute dose of ethanol (5.8 g/kg) or an isocaloric amount of maltose-dextrine on day 9 of pregnancy. Litters were removed on day 18 of pregnancy and examined for gross, soft-tissue, and skeletal malformations. Results showed that ethanol-exposed B6 litters had a higher percentage of digit (19%), kidney (24%), and skeletal (32%, mostly vertebral) malformations than their maltose-exposed controls (7% or below). Prenatal exposure to ethanol increased skeletal (68%, both rib and vertebral) malformations for A litters when compared to their maltose-exposed controls (4%), but did not increase digit or kidney malformations. Ethanol-exposed D2 litters did not differ from maltose-exposed controls. Maternal blood ethanol levels did not differ among the B6, D2, and A strains. These results provide additional evidence suggesting a genetic component to ethanol teratogenesis.

Impact of zinc supplementation on the improvement of ethanol tolerance and yield of self-flocculating yeast in continuous ethanol fermentation.

PubMed

Zhao, X Q; Xue, C; Ge, X M; Yuan, W J; Wang, J Y; Bai, F W

2009-01-01

The effects of zinc supplementation were investigated in the continuous ethanol fermentation using self-flocculating yeast. Zinc sulfate was added at the concentrations of 0.01, 0.05 and 0.1 g l(-1), respectively. Reduced average floc sizes were observed in all the zinc-supplemented cultures. Both the ethanol tolerance and thermal tolerance were significantly improved by zinc supplements, which correlated well with the increased ergosterol and trehalose contents in the yeast flocs. The highest ethanol concentration by 0.05 g l(-1) zinc sulfate supplementation attained 114.5 g l(-1), in contrast to 104.1 g l(-1) in the control culture. Glycerol production was decreased by zinc supplementations, with the lowest level 3.21 g l(-1), about 58% of the control. Zinc content in yeast cells was about 1.4 microMol g(-1) dry cell weight, about sixfold higher than that of control in all the zinc-supplemented cultures, and close correlation of zinc content in yeast cells with the cell viability against ethanol and heat shock treatment was observed. These studies suggest that exogenous zinc addition led to a reprogramming of cellular metabolic network, resulting in enhanced ethanol tolerance and ethanol production.

Altered spatial learning and delay discounting in a rat model of human third trimester binge ethanol exposure

PubMed Central

Bañuelos, Cristina; Gilbert, Ryan J.; Montgomery, Karienn S.; Fincher, Annette S.; Wang, Haiying; Frye, Gerald D.; Setlow, Barry; Bizon, Jennifer L.

2012-01-01

Ethanol exposure during perinatal development can cause cognitive abnormalities including difficulties in learning, attention, and memory, as well as heightened impulsivity. The purpose of this study was to assess performance in spatial learning and impulsive choice tasks in rats subjected to an intragastric intubation model of binge ethanol exposure during human third trimester-equivalent brain development. Male and female Sprague–Dawley rat pups were intubated with ethanol (5.25 g/kg/day) on postnatal days 4–9. At adolescence (between postnatal days 35–38), these rats and sham intubated within-litter controls were trained in both spatial and cued versions of the Morris water maze. A subset of the male rats was subsequently tested on a delay-discounting task to assess impulsive choice. Ethanol-exposed rats were spatially impaired relative to controls, but performed comparably to controls on the cued version of the water maze. Ethanol-exposed rats also showed greater preference for large delayed rewards on the delay discounting task, but no evidence for altered reward sensitivity or perseverative behavior. These data demonstrate that early postnatal intermittent binge-like ethanol exposure has prolonged, detrimental, but selective effects on cognition, suggesting that even relatively brief ethanol exposure late in human pregnancy can be deleterious for cognitive function. PMID:22129556

Effect of prenatal exposure to ethanol on the ultrastructure of layer V of mature rat somatosensory cortex.

PubMed

al-Rabiai, S; Miller, M W

1989-12-01

Recent data have shown that the structure and function of layer V pyramidal neurons, e.g. corticospinal neurons, is altered by prenatal exposure to ethanol. We examined the effect of ethanol on the ultrastructure of layer V in somatosensory cortex. Timed pregnant rats were fed a diet containing 6.7% (v/v) ethanol (E) or pair-fed a nutritionally matched control diet (C). Thirty-day-old offspring of these mothers were prepared by standard electron microscopic techniques. The somata of pyramidal and local circuit neurons and the neuropil were analysed. Prenatal exposure to ethanol induced alterations in the somata of both populations of neurons. The parallel stacking of cisternae characteristic of C-treated rats was disorganized in E-treated rats. Moreover, the Golgi complex and lysosomes occupied a larger fraction of the somata of E-treated rats. The number and frequency of symmetric axosomatic synapses, but not asymmetric axosomatic synapses, formed by both types of neurons were significantly greater in E-treated rats. Gestational exposure to ethanol produced a variety of changes in the neuropil. Dendrites, particularly dendritic shafts, occupied less space in E-treated rats. In contrast, axons accounted for significantly more of the neuropil in E-treated rats than in controls. This increase in axonal space was due to a significantly greater coverage by non-myelinated axons and a significantly smaller coverage by myelinated axons in E-treated rats than in C-treated rats. Although the overall frequency of synapses was similar in both treatment groups, there were significantly more asymmetric synapses in E-treated rats, and most of these were axospinous synapses. These differences may contribute to documented physiological changes such as the lower rate of glucose utilization in layer V of somatosensory cortex of E-treated rats and they may underlie the mental retardation which is characteristic of children with foetal alcohol syndrome.

Postnatal handling does not normalize hypothalamic corticotropin-releasing factor mRNA levels in animals prenatally exposed to ethanol.

PubMed

Gabriel, Kara I; Glavas, Maria M; Ellis, Linda; Weinberg, Joanne

2005-06-09

Postnatal handling has been shown to attenuate some of the deficits in developmental outcome observed following prenatal ethanol exposure (E) although it appears to be ineffective at ameliorating the hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors that has been observed in adult E animals. However, the effects of postnatal handling on central regulation of HPA activity in E animals, particularly with regard to alterations in steady-state hypothalamic corticotropin-releasing factor (CRF) activity, have not been examined. In the present study, offspring from E, pair-fed (PF), and ad-libitum-fed control (C) groups were exposed to daily handling during the first 2 weeks of life (H) or were left entirely undisturbed until weaning (NH). Basal CRF and arginine vasopressin (AVP) mRNA in the parvocellular portion of the paraventricular nucleus (pPVN) of the hypothalamus were assessed at 90-110 days of age. Prenatal ethanol exposure resulted in elevated basal pPVN CRF mRNA levels compared to those in ad-libitum-fed controls. Handling altered CRF mRNA levels in a sex-specific and prenatal treatment-specific manner. Females showed no significant effects of handling. In contrast, handling decreased CRF mRNA levels in PF and C but not E males compared to their NH counterparts. There were no effects of prenatal ethanol or postnatal handling on AVP mRNA levels. These findings indicate that prenatal ethanol exposure results in elevated basal CRF mRNA levels in adulthood and that handling appears to be ineffective in normalizing those elevations, supporting the suggestion that altered basal HPA regulation in E animals may, at least in part, underlie their HPA hyperresponsiveness to stressors.

Hops (Humulus lupulus) Content in Beer Modulates Effects of Beer on the Liver After Acute Ingestion in Female Mice.

PubMed

Landmann, Marianne; Sellmann, Cathrin; Engstler, Anna Janina; Ziegenhardt, Doreen; Jung, Finn; Brombach, Christine; Bergheim, Ina

2017-01-01

Using a binge-drinking mouse model, we aimed to determine whether hops (Humulus lupulus) in beer is involved in the less damaging effects of acute beer consumption on the liver in comparison with ethanol. Female C57BL/6 J mice were either fed one iso-alcoholic and iso-caloric bolus dose of ethanol, beer, beer without hops (6 g ethanol/kg body weight) or an iso-caloric bolus of maltodextrin control solution. Markers of steatosis, intestinal barrier function, activation of toll-like receptor 4 signaling cascades, lipid peroxidation and lipogenesis were determined in liver, small intestine and plasma 2 h and 12 h after acute alcohol ingestion. Alcohol-induced hepatic fat accumulation was significantly attenuated in mice fed beer whereas in those fed beer without hops, hepatic fat accumulation was similar to that found in ethanol-fed mice. While markers of intestinal barrier function e.g. portal endotoxin levels and lipogenesis only differed slightly between groups, hepatic concentrations of myeloid differentiation primary response gene 88, inducible nitric oxide synthase (iNOS) and plasminogen-activator inhibitor 1 protein as well as of 4-hydroxynonenal and 3-nitrotyrosine protein adducts were similarly elevated in livers of mice fed ethanol or beer without hops when compared with controls. Induction of these markers was markedly attenuated in mice fed hops-containing beer. Taken together, our data suggest that hops in beer markedly attenuated acute alcohol-induced liver steatosis in female mice through mechanisms involving a suppression of iNOS induction in the liver. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Hepatotoxicity of illegal home-made alcohols.

PubMed

Gökce, Hasan; Akcan, Ramazan; Celikel, Adnan; Zeren, Cem; Ortanca, Ibrahim; Demirkiran, Sumeyra

2016-10-01

Alcohol-related hepatotoxicity is not only caused by excessive alcohol consumption but also caused and even accelerated by hepatotoxic ingredients other than ethanol. Concentrations of hepatotoxic substances might be significantly high, particularly in illegally produced home-made alcohols. In this study we aim to analyze the hepatotoxic effects of a home-made alcohol traditionally called "bogma raki" in Turkey. Fifty Wistar albino male rats were used. Five groups were randomly formed with ten animals in each. Besides laboratory diets, groups were fed as follows: Group 1 (control group) distilled water; Group 2 bogma raki with distilled water (%44 (v/v), 9.2 ml/kg/day); Group 3 bogma raki with distilled water (%44 (v/v), 9.2 ml/kg/day)+walnut (10 g/kg/day); Group 4 whisky with distilled water (%40 (v/v), 9.2 ml/kg/day); Group 5 distilled water + walnut (10 g/kg/day), for 28 days. The toxicological analysis of The spirits were analyzed using Hewlett-Packard (Palo Alto, CA) GC/MS system with HP 6890 gas chromatograph, an HP 5972 mass selective detector (MSD) and an HP 6890 automatic liquid sampler GC/MS; the pressure of the carrier gas helium was 6.0 bar and the split value with a ratio of 1:100. The injection unit temperature set to 250 °C and MS quadrupole temperature set to 280 °C. The MS quadrupole detector ionization energy set to 70 eV. The initial column temperature was 60 °C (for 4 min) programmed by 6 °C/min to final temperature 160 °C and kept for 8 min at 160 °C. Utilized whisky and bogma raki samples were analyzed for the amounts of trans-anethole, ethanol, methanol, 1-propanolol, butanol, 2-butanol, 2-methyl-1-propanolol (isobutanol) and 3-methylbutanol (isoamyl alcohol). Histopathological changes in liver tissues were graded as follows; normal = 0 (<10%), mild = 1 (10%-40%), moderate = 2 (40%-70%), severe = 3 (above 70%). Chemical composition of illegally produced raki sample (%v/v) was as follows: trans-anethole %1.93, ethanol %95.70, 2-methyl-1-propanolol (isobutanol) %0.19, asetic acid %0.25, 3-methylbutanol (isoamyl alcohol) %0.77, and others %1.16. Chemical composition of commercial whisky sample (%v/v) was as follows: ethanol %97.72, 2-methyl-1-propanolol (isobutanol) %0.57, asetic acid %0.23, 3-methylbutanol (isoamyl alcohol) %1.28, and others %0.2. No traces of trans-anethole were detected in whisky. Normal liver morphology was recorded in control and walnut groups. However, bogma raki caused significant congestion and inflammatory cell infiltration compared to control and walnut group. On the other hand, whisky administration caused mild degeneration including inflammation in a limited area. Obtained findings suggest that trans-anethole containing alcoholic beverages are more hepatotoxic compared to commercial alcoholic beverages. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

In vitro antioxidant and in vivo hepatoprotective activity of leave extract of Raphanus sativus in rats using CCL4 model.

PubMed

Syed, Shariq Naeem; Rizvi, Waseem; Kumar, Anil; Khan, Aijaz Ahmad; Moin, Shagufta; Ahsan, Akif

2014-01-01

Raphanus sativus is reported to have a variety of biological activities. This work screened the hepato-protective and antioxidant activity of ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in Carbon tetrachloride (CCl4), model in rats. The extracts were subjected to antioxidant tests (Total reducing power and Total phenolic content), and preliminary phytochemical screening. A pilot study was done on 100 and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The albino rats (200-250 grams), were divided into 5 groups of 6 animals each (n=6). There were three control groups comprising of normal control (normal saline -1ml/kg), negative control group (CCl4 1ml/kg in olive oil in a ratio of 1:1 v/v), and positive control group (Silymarin 50mg/kg). The Test drugs were given in a dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done. The phytochemical study showed the presence of flavanoids, terpenoids, alkaloids, saponins and sterols. A dose dependent increase in the oxidative potential was observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (p<0.001) increase in levels of AST, ALT and alkaline phosphatase as compared to negative control (percentage hepatoprotection =45.3%) while ARS 300 mg/kg (p<.01) group showed 30% hepatoprotection. The GSH (p<0.001) and CAT (p<0.05) in ERS and ARS were significantly increased while MDA levels were decreased (P< 0.01), as compared negative control. The findings were confirmed histo-pathological examination. The ethanol and aqueous extract of Raphanus sativus have partial hepatoprotection against CCl4 toxicity.

Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol

PubMed Central

Lopez, M. F.; Becker, H. C.; Chandler, L. J.

2014-01-01

Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol. PMID:25266936

Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

PubMed

Lennernäs, Hans

2009-01-01

Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is almost impossible to predict and will depend on drinking behavior and the highly variable gastrointestinal factors of importance for dissolution, transit and absorption. Therefore, controlled release products which show a vulnerability to ethanol during two hours in vitro should be required to demonstrate clinical safety by going through in vivo testing with an alcoholic beverage of up to 40% ethanol and of a sufficient volume (probably 120 mL or more), consumed in a relatively short period of time. Alternatively, such preparations should be reformulated in accordance with quality-by-design principles.

Effects of prenatal binge-like ethanol exposure and maternal stress on postnatal morphological development of hippocampal neurons in rats.

PubMed

Jakubowska-Dogru, Ewa; Elibol, Birsen; Dursun, Ilknur; Yürüker, Sinan

2017-10-01

Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months. Ethanol was administered to the pregnant Wistar dams intragastrically, throughout gestation days (GD) 7-20, at a total dose of 6g/kg/day resulting in the mean blood alcohol concentration (BAC) of 246.6±40.9mg/dl. Ten morphometric parameters of Golgi-stained hippocampal neurons (pyramidal and granule) from CA1, CA3, and DG areas were examined at critical postnatal days (PD): at birth (PD1), at the end of the brain growth spurt period (PD10), in juveniles (PD30), and in young adults (PD60). During postnatal development, the temporal pattern of morphometric changes was shown to be region-dependent with most significant alterations observed between PD1-30 in the CA region and between PD10-30 in the DG region. It was also parameter-dependent with the soma size (except for CA3 pyramids), number of primary dendrites, dendrite diameter, dendritic tortuosity and the branch angle demonstrating little changes, while the total dendritic field area, dendritic length, number of dendritic bifurcations, and spine density being highly increased in all hippocampal regions during the first postnatal month. Moderate ethanol intoxication and the maternal intubation stress during gestation, showed similar, transient effects on the neuron development manifested as a smaller soma size in granule cells, reduced dendritic parameters and lower spine density in pyramidal neurons at PD1. Full recovery from these effects took place within the first 10 postnatal days. This study showed regional and temporal differences in the development of different morphometric features of principal hippocampal neurons in intact subjects over a protracted 2-months postnatal period. It also demonstrated an overlap in the effects of a moderate fetal ethanol intoxication and a mild maternal stress produced by the intragastric intubation, a commonly used method of ethanol administration to the pregnant dams. Fast recovery from the adverse effects on the soma size, dendritic arborization and spines density observed at birth indicates towards the fetal ethanol/stress induced developmental retardation. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

The effects of age at the onset of drinking to intoxication and chronic ethanol self-administration in male rhesus macaques

PubMed Central

Helms, Christa M.; Rau, Andrew; Shaw, Jessica; Stull, Cara; Gonzales, Steven W.; Grant, Kathleen A.

2014-01-01

Rationale Consumption of alcohol begins during late adolescence in a majority of humans, and the greatest drinking occurs at 18–25 years then decreases with age. Objectives The present study measured differences in ethanol intake in relation to age at the onset of ethanol access among non-human primates to control for self-selection in humans and isolate age effects on heavy drinking. Methods Male rhesus macaques were assigned first access to ethanol during late adolescence (n = 8), young adulthood (n = 8) or early middle age (n = 11). The monkeys were induced to drink ethanol (4% w/v in water) in increasing doses (water, 0.5 g/kg, 1.0 g/kg, 1.5 g/kg) using a fixed-time (FT) 300-s schedule of food delivery, followed by 22 hours/day concurrent access to ethanol and water for 12 months. Age-matched controls consumed isocaloric maltose-dextrin solution yoked to the late adolescents, expected to be rapidly maturing (n = 4). Results Young adult monkeys had the greatest daily ethanol intake and blood-ethanol concentration (BEC). Only late adolescents escalated their intake (ethanol, not water) during the second compared to the first 6 months of access. On average, testosterone was consistent with age differences in maturation, and tended to increase throughout the experiment more for control than ethanol-drinking adolescent monkeys. Conclusions Young adulthood in non-human primates strongly disposes toward heavy drinking independently of sociocultural factors present in humans. Drinking ethanol to intoxication during the critical period of late adolescence is associated with escalation to heavy drinking. PMID:24448900

Physiological response and semen quality of rabbit bucks supplemented with Moringa leaves ethanolic extract during summer season.

PubMed

El-Desoky, N I; Hashem, N M; Elkomy, A; Abo-Elezz, Z R

2017-09-01

Exposure of rabbit bucks to summer heat stress reduces their homeostasis and semen quality leading to a temporal subfertility. The potentiality of ethanolic extract of Moringa oleifera leaves (M. oleifera ethanolic extract (MLEE)) to reduce negative impacts of heat stress on physiological and semen quality traits was investigated. A total of 28 adult V-line rabbit bucks were randomly distributed among four experimental groups of seven rabbits each. The first group received water (placebo) and served as a control (M0). The other three groups were given orally MLEE at levels of 50 (M50), 100 (M100) and 150 (M150) mg/kg BW every other day for 12 consecutive weeks during the summer season. Chemical constituents of MLEE were detected by gas chromatography/MS. During the experimental period, ambient temperature and relative humidity were recorded daily and were used to estimate temperature and humidity index. Feed intake, BW, rectal temperature were recorded and blood serum biochemical attributes were determined. Semen samples were collected weekly and were analyzed for semen quality traits. Results showed that MLEE contained high percentages of long-chain fatty acids and antioxidant agents. Feed intake and BW were not affected significantly by the treatment, however rectal temperature was decreased significantly by 0.42°C, 0.24°C and 0.40°C in the M50, M100 and M150 groups, respectively, compared with the M0 group. Treatment with 50 mg/kg BW increased concentration of serum albumin (115%; P<0.05), total antioxidant capacity (132%; P<0.05) and testosterone (160%; P=0.098) as well as seminal plasma initial fructose (127%; P=0.092) compared with the control group. Compared with the control, MLEE supplementation with 50, 100 and 150 mg/kg BW increased significantly sperm concentration by 118%, 151% and 158%, sperm progressive motility by 117%, 120% and 118%, sperm viability by 129%, 137% and 127%, sperm normal morphology by 114%, 113% and 114%, intact acrosome sperm by 109% (on average) and sperm with integrated cell membrane by 109%, 123% and 114%, respectively. In conclusion, MLEE supplementation at a level of 50 mg/kg BW could be effectively used to improve heat tolerance, oxidative status and semen quality of rabbit bucks during summer season.

Influence of ethanol vapor addition on the surface modification of polyethylene in a dielectric barrier discharge

NASA Astrophysics Data System (ADS)

Van Deynse, Annick; Morent, Rino; Leys, Christophe; De Geyter, Nathalie

2017-10-01

In this paper, ethanol vapor up to 50% is added to an argon, air or nitrogen dielectric barrier discharge at medium pressure to profoundly investigate the effect of ethanol addition on the surface modification of low density polyethylene (LDPE). Water contact angle (WCA) and X-ray photoelectron spectroscopy (XPS) measurements show that the ethanol vapor addition effect on the LDPE surface depends on the used carrier gas. Adding ethanol to an argon plasma has no significant effect on the wettability nor on the chemical composition of LDPE compared to a pure argon plasma treatment. Ethanol addition does however slightly increase the LDPE surface roughness. Addition of small amounts of ethanol vapor to an air plasma makes it possible to incorporate additional nitrogen and oxygen groups on the LDPE surface, resulting in an extra decrease of 11% in WCA value. Moreover, the LDPE surface roughness is slightly increased due to the ethanol vapor addition. The most significant effect of ethanol addition is however observed when nitrogen is used as carrier gas. After an N2/2% ethanol plasma treatment, an 85% reduction in WCA value to 8.5° is found compared to a pure N2 plasma treatment. This very hydrophilic LDPE surface is obtained due to a significantly high incorporation of oxygen and nitrogen groups on the surface with an O/C and N/C ratio reaching 32% and 53% respectively. FTIR measurements also reveal that the observed extremely high wettability of LDPE is not the result of plasma activation but is due to plasma polymerization effects occurring on the surface resulting into the deposition of a plasma polymer containing ketones, amides as well as Cdbnd N groups. In addition, ageing studies have also been conducted and these studies reveal that for all carrier gases, ethanol addition to the discharge gas significantly suppresses the ageing effect. All the above mentioned conclusions therefore indicate that ethanol vapor based plasmas can be an excellent tool to increase the surface energy of polymers.

Ethanol extract of Moringa oliefera prevents in vitro glucose induced cataract on isolated goat eye lens.

PubMed

Kurmi, Raghvendra; Ganeshpurkar, Aditya; Bansal, Divya; Agnihotri, Abhishek; Dubey, Nazneen

2014-02-01

The aim of current work was to evaluate in vitro anticataract potential of Moringa oliefera extract. Goat eye lenses were divided into 4 groups; Group served as control, Group II as toxic control, Group III and Group IV were incubated in extract (250 μg/ml and 500 μg/ml of extract of M. oliefera) Group II, III and IV were incubated in 55 mM glucose in artificial aqueous humor to induce lens opacification. Estimation of total, water soluble protein, catalase, glutathione and malondialdehyde along with photographic evaluation of lens was done. Group II (toxic control) lenses showed high amount of MDA (Malondialdehyde), soluble, insoluble protein, decreased catalase and glutathione levels, while lenses treated with Moringa oliefera extract (Group III and Group IV) showed significant (FNx01 P < 0.05) reduction in MDA and increased level of catalase, glutathione, total and soluble protein. Results of present findings suggest protective effect of Moringa oliefera in prevention of in vitro glucose induced cataract.

Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury

PubMed Central

Duncan, Jeremy W.; Zhang, Xiao; Wang, Niping; Johnson, Shakevia; Harris, Sharonda; Udemgba, Chinelo; Ou, Xiao-Ming; Youdim, Moussa B.; Stockmeier, Craig A.; Wang, Jun Ming

2016-01-01

Binge drinking induces several neurotoxic consequences including oxidative stress and neurodegeneration. Because of these effects, drugs which prevent ethanol-induced damage to the brain may be clinically beneficial. In this study, we investigated the ethanol-mediated KLF11-MAO cell death cascade in the frontal cortex of Sprague–Dawley rats exposed to a modified Majchowicz 4-day binge ethanol model and control rats. Moreover, MAO inhibitors (MAOIs) were investigated for neuroprotective activity against binge ethanol. Binge ethanol-treated rats demonstrated a significant increase in KLF11, both MAO isoforms, protein oxidation and caspase-3, as well as a reduction in BDNF expression in the frontal cortex compared to control rats. MAOIs prevented these binge ethanol-induced changes, suggesting a neuroprotective benefit. Neither binge ethanol nor MAOI treatment significantly affected protein expression levels of the oxidative stress enzymes, SOD2 or catalase. Furthermore, ethanol-induced antinociception was enhanced following exposure to the 4-day ethanol binge. These results demonstrate that the KLF11-MAO pathway is activated by binge ethanol exposure and MAOIs are neuroprotective by preventing the binge ethanol-induced changes associated with this cell death cascade. This study supports KLF11-MAO as a mechanism of ethanol-induced neurotoxicity and cell death that could be targeted with MAOI drug therapy to alleviate alcohol-related brain injury. Further examination of MAOIs to reduce alcohol use disorder-related brain injury could provide pivotal insight to future pharmacotherapeutic opportunities. PMID:26805422

Electrolyzed-reduced water inhibits acute ethanol-induced hangovers in Sprague-Dawley rats.

PubMed

Park, Seung-Kyu; Qi, Xu-Feng; Song, Soon-Bong; Kim, Dong-Heui; Teng, Yung-Chien; Yoon, Yang-Suk; Kim, Kwang-Yong; Li, Jian-Hong; Jin, Dan; Lee, Kyu-Jae

2009-10-01

Ethanol consumption disturbs the balance between the pro- and anti-oxidant systems of the organism, leading to oxidative stress. Electrolyzed-reduced water (ERW) is widely used by people in East Asia for drinking purposes because of its therapeutic properties including scavenging effect of reactive oxygen species. This study was performed to investigate the effect of ERW on acute ethanol-induced hangovers in Sprague-Dawley rats. Alcohol concentration in serum of ERW-treated rats showed significant difference at 1 h, 3 h and 5 h respectively as compared with the rats treated with distilled water. Both alcohol dehydrogenase type 1 and acetaldehyde dehydrogenase related with oxidation of alcohol were significantly increased in liver tissue while the level of aspartate aminotransferase and alanine aminotransferase in serum was markedly decreased 24 h after pre-oral administration of ERW. Moreover, oral administration of ERW significantly activated non-ezymatic (glutathione) and enzymatic (glutathione peroxidase, glutathione-S-transferase, Cu/Zn-superoxide dismutase and catalase) antioxidants in liver tissues compared with the control group. These results suggest that drinking ERW has an effect of alcohol detoxification by antioxidant mechanism and has potentiality for relief of ethanol-induced hangover symptoms.

Nephroprotective effect of Bauhinia variegata (Linn.) whole stem extract against cisplatin-induced nephropathy in rats

PubMed Central

Pani, Saumya R.; Mishra, Satyaranjan; Sahoo, Sabuj; Panda, Prasana K.

2011-01-01

The nephroprotective activity of the ethanolic extract of Bauhinia variegata (Linn.) whole stem against cisplatin-induced nephropathy was investigated by an in vivo method in rats. Acute nephrotoxicity was induced by i.p. injection of cisplatin (7 mg/kg of body weight (b.w.)). Administration of ethanol extract at dose levels of 400 and 200 mg/kg (b.w.) to cisplatin-intoxicated rats for 14 days attenuated the biochemical and histological signs of nephrotoxicity of cisplatin in a dose-dependent fashion. Ethanol extract at 400 mg/kg decreased the serum level of creatinine (0.65 ± 0.09; P<0.001) and urea (32.86 ± 5.88; P<0.001) associated with a significant increase in body weight (7.16 ± 1.10; P<0.001) and urine volume output (11.95 ± 0.79; P<0.05) as compared to the toxic control group. The ethanol extract of B. variegata at 400 mg/kg (b.w.) exhibited significant and comparable nephroprotective potential to that of the standard polyherbal drug cystone. The statistically (one-way-ANOVA followed by Tukey-Kramer multiple comparison) processed results suggested the protective action of B. variegate whole stem against cisplatin-induced nephropathy. PMID:21572659

Exploring the role of curcumin containing ethanolic extract obtained from Curcuma longa (rhizomes) against retardation of wound healing process by aspirin

PubMed Central

Pawar, Rajesh Singh; Toppo, Fedelic Ashish; Mandloi, Avinash Singh; Shaikh, Shabnam

2015-01-01

Aim: The aim of the study was to assess the curcumin containing ethanolic extract (EtOH) obtained from Curcuma longa (Cl) against retardation of wound healing by aspirin. Materials and Methods: Wound healing process was retarded by administering the dose of 150 mg/kg body weight of aspirin orally for 9 days to observe the effect of EtOH obtained from Cl using excision and incision wound model in rats. The various parameters such as % wound contraction, epithelialization period, hydroxyproline, tensile strength were observed at variant time intervals and histopathological study was also performed. Results: Curcumin containing 5% and 10% ethanolic extract ointment have shown significant (P < 0.01) wound healing activity against an aspirin (administered 150 mg/kg body weight orally for 9 days) retarded wound healing process. Topical application of ointment showed significant (P < 0.01) difference as compared to the control group. Histopathological studies also showed healing of the epidermis, increased collagen, fibroblasts and blood vessels. Conclusion: Ethanolic extract of Cl ointment (EtOHCl) containing 10% curcumin displayed remarkable healing process against wound retardation by aspirin. PMID:25878374

Absence of toxicity and genotoxicity in an extract of Rubus coriifolius.

PubMed

González-Hernández, S; González-Ramírez, D; Dávila-Rodríguez, M I; Jimenez-Arellanez, A; Meckes-Fischer, M; Said-Fernández, S; Cortés-Gutiérrez, E I

2016-12-02

Rubus coriifolius Focke is a wild plant from the Rosaceae family. It grows in both Guatemala and Mexico. The polar extract of the aerial parts of this plant has antibacterial, anti-inflammatory, and anti-protozoal activities. These properties may explain the traditional use of this plant. In vivo and in vitro assays were used to assess the genotoxic and toxic effects of an ethanol extract of the aerial parts of R. coriifolius. Three groups of rats were orally administered the R. coriifolius extract diluted in ethanol (5%) at doses of 1.89 mg/kg body weight (low dose), 4.72 mg/kg body weight (medium dose), and 9.44 mg/kg body weight (high dose) for 3 weeks. Genotoxic/cytotoxic effects induced by the R. coriifolius ethanol extract were evaluated in vivo by a micronuclei (MN) test in rat's bone marrow cells and in vitro by MN and sister chromatid exchange (SCE) in human lymphocyte cultures. In vivo genotoxicity analyses revealed that the average number of micronucleated polychromatic erythrocytes and the polychromatic erythrocyte/red blood cell ratio at all doses were not significantly different from those of the negative control. In vitro genotoxicity analyses showed that MN, SCE, and proliferative index frequencies in a human lymphocyte cell culture were not significantly different from those of the negative control. These results demonstrate that the ethanol extract of R. coriifolius aerial parts is not toxic or mutagenic (in vitro and in vivo) and does not affect cell proliferation at the concentrations analyzed.

Maternal ethanol consumption reduces Se antioxidant function in placenta and liver of embryos and breastfeeding pups.

PubMed

Nogales, Fátima; Ojeda, M Luisa; Jotty, Karick; Murillo, M Luisa; Carreras, Olimpia

2017-12-01

The fetal alcohol exposition during pregnancy leads to different disorders in offspring, related to the oxidative stress generated by alcohol. It is well-documented that there is an impairment of the antioxidant selenoprotein Glutathione peroxidase (GPx) activity in ethanol offspring during the embryo period, although no-one has described Selenium (Se) status. The aim is to analyze for the first time Se deposits in vivo and Se's biological implication in embryos and placenta after alcohol exposure and in offspring whose mothers continued to drink ethanol during lactation. Se deposits, GPx and glutathione reductase (GR) activity, lipid and protein oxidation and the expression of GPx1 were measured in placenta and liver of both embryos (E-19) and breastfeeding pups (L-21) in control and ethanol groups (20% v/v). Ethanol consumption decreased Se deposits, GPx activity and GPx1 expression, while increasing biomolecular oxidation in placenta and in the liver of E-19 and L-21. The GR/GPx ratio decreased in placenta and in E-19, together with an increase in lipid oxidation, while increased in the liver of L-21 pups with protein oxidation. Ethanol also decreased the GPx1 expression/GPx activity ratio in the liver of E-19 and L-21, indicating that alcohol decreases GPx activity by both depleting Se deposits and promoting GPx inactivation. In placenta GPx activity is proportional to the GPx1 expression found, so the ethanol affects GPx activity in offspring more than in dams. Therefore, Se supplementation therapy in dams could contribute as an interesting antioxidant that prevents fetal alcohol syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.

Supplemental choline does not attenuate the effects of neonatal ethanol administration on habituation of the heart rate orienting response in rats.

PubMed

Hunt, Pamela S; Jacobson, Sarah E; Kim, Sarah

2014-01-01

Several studies using rodent subjects have now shown that extra dietary choline may prevent or even reverse the deleterious effects of pre- and early post-natal ethanol administration. Choline supplementation has been shown to attenuate many, although not all, of ethanol's effects on brain development and behavior. Our laboratory has consistently reported impaired habituation of the heart rate orienting response to a novel olfactory stimulus in animals exposed to ethanol on postnatal days (PD) 4-9. Here we examine whether supplemental choline given both during and after ethanol administration could alleviate these ethanol-induced deficits. Subjects were given 5g/kg/day ethanol or sham intubations on PD 4-9. Half of the subjects in each group were given a single daily s.c. injection of choline chloride on PD 4-20, while the other half were injected daily with saline. Pups were tested for heart rate orienting and response habituation in a single test session on PD 23. Results replicated the ethanol-induced impairment in response habituation. However, choline supplementation had no effect on orienting or habituation in either neonatal treatment group. These findings indicate that habituation deficits induced by ethanol are not alleviated by extra dietary choline using these parameters. Choline holds great promise as a treatment for some fetal alcohol effects, but is not an effective treatment for all ethanol-related deficits. Copyright © 2014 Elsevier Inc. All rights reserved.

Differences in sensitivity to ethanol-induced conditioned taste aversions emerge after pre- or post-pubertal gonadectomy in male and female rats.

PubMed

Morales, Melissa; Spear, Linda P

2013-03-01

We have previously demonstrated that gonadectomy either prior to (early) or after (late) puberty elevated ethanol consumption in males to levels similar to intact adult females-effects that were attenuated by testosterone replacement. To assess whether alterations in the aversive effects of ethanol might contribute to gonadectomy-associated increases in ethanol intake in males, the present study examined the impact of gonadectomy on conditioned taste aversions (CTA) to ethanol in male and female Sprague-Dawley rats. Animals were gonadectomized, received sham surgery (SH) or non-manipulated (NM) on postnatal (P) day 23 (early) or 67 (late) and tested for CTA to ethanol in adulthood. Water-deprived rats were given 1 hr access every-other-day to 10% sucrose followed by an injection of ethanol (0, 1g/kg) for 5 test sessions. Test data were analyzed to determine the first day significant aversions emerged in each ethanol group (i.e., sucrose intakes significantly less than their saline-injected counterparts). Early gonadectomized males acquired the CTA more rapidly than did early SH and NM males (day 1 vs 3 and 4 respectively), whereas a gonadectomy-associated enhancement in ethanol CTA was not evident in late males. Among females, gonadectomy had little impact on ethanol-induced CTA, with females in all groups showing an aversion by the first or second day, regardless of surgery age. These data suggest that previously observed elevations in ethanol intake induced by either pre- or post-pubertal gonadectomy in males are not related simply to gonadectomy-induced alterations in the aversive effects of ethanol indexed via CTA. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of Vernonia amygdalina Del. Leaf Ethanolic Extract on Intoxicated Male Wistar Rats Liver

PubMed Central

Iwo, Maria Immaculata; Sjahlim, Sergia Louisa; Rahmawati, Siti Farah

2017-01-01

Vernonia amygdalina has been shown to have antioxidant activity, and is also expected to have hepatoprotective activity. This study was conducted to study the effect of V. amygdalina ethanol extracts on intoxicated rat livers. Fresh leaves were extracted in ethanol, and the hepatoprotective activity was tested on male Wistar rats induced with a combination of isoniazid (INH) and rifampicin. Parameters observed were the activity of the enzyme alanine transferase (ALT), serum albumin levels, liver index, and histopathological of the rat liver. The results showed that 50 and 100 mg/kg rat body weight of V. amygdalina ethanol extracts could prevent liver intoxication, starting on day 14. Based on serum albumin concentrations and ALT activity, the high dose extract (100 mg/kg) was more potent as a hepatoprotective agent compared to the extract at a low dose (50 mg/kg). The group of rats treated with a high dose extract showed normal liver index compared to the positive control. Through histology examination, the liver of rats treated with a high dose extract (100 mg/kg) showed minimal liver cell structure damage, and showed similar patterns to the normal rat. Based on these results, it can be concluded that V. amygdalina ethanol extracts can be used to protect the liver in a combination of INH and rifampicin as antituberculosis treatment. PMID:28333116

Effect of Vernonia amygdalina Del. Leaf Ethanolic Extract on Intoxicated Male Wistar Rats Liver.

PubMed

Iwo, Maria Immaculata; Sjahlim, Sergia Louisa; Rahmawati, Siti Farah

2017-03-23

Vernonia amygdalina has been shown to have antioxidant activity, and is also expected to have hepatoprotective activity. This study was conducted to study the effect of V. amygdalina ethanol extracts on intoxicated rat livers. Fresh leaves were extracted in ethanol, and the hepatoprotective activity was tested on male Wistar rats induced with a combination of isoniazid (INH) and rifampicin. Parameters observed were the activity of the enzyme alanine transferase (ALT), serum albumin levels, liver index, and histopathological of the rat liver. The results showed that 50 and 100 mg/kg rat body weight of V. amygdalina ethanol extracts could prevent liver intoxication, starting on day 14. Based on serum albumin concentrations and ALT activity, the high dose extract (100 mg/kg) was more potent as a hepatoprotective agent compared to the extract at a low dose (50 mg/kg). The group of rats treated with a high dose extract showed normal liver index compared to the positive control. Through histology examination, the liver of rats treated with a high dose extract (100 mg/kg) showed minimal liver cell structure damage, and showed similar patterns to the normal rat. Based on these results, it can be concluded that V. amygdalina ethanol extracts can be used to protect the liver in a combination of INH and rifampicin as antituberculosis treatment.

Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increasedmore » pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.« less

Serum calcium, phosphorus and magnesium responses to massive dosing of cholecalciferol (CC) and 25-OH-CC in young and aged ewes.

PubMed

Thomas, B B; Boling, J A; Muir, W M

1981-01-01

Twenty-four ewes were divided into two age groups (one-year-old and nine-year-old) and used to determine the influence of cholecalciferol (CC) and 25-OH-CC on serum concentrations of Ca, P, and Mg with time post-injection. The ewes were maintained in slatted-floor pens and fed 800 g per head daily of a diet which analyzed 0.38% calcium, 0.31% phosphorus, and 0.14% magnesium. This diet was fed throughout the 21-day trial. The ewes were injected on days 0 and 7 as follows: (control) 5 ml ethanol; (CC) 50 mg CC in 5 ml ethanol; and (25-OH-CC) 25 mg 25-OH-CC in ethanol. Blood samples were pre-injection (day 0) and on days 1, 2, 3, 5, 7, 9, 12, 17 and 21 of the trial. Serum Ca averaged 10.81, 11.06 and 11.25 mg/100 ml for the one-year-old ewes and 10.51, 11.06 and 11.54 mg/100 ml for the nine-year-olds across sampling times in groups A to C, respectively. Serum P across sampling times averaged 6.58, 7.80 and 9.51 mg/100 ml in one-year-old ewes and were different (P less than .05) from each other. Serum P averaged 7.06, 8.56 and 8.59 mg/100 ml for the nine-year-old ewes. Serum Mg values were 2.51, 2.32 and 2.19 mg/100 ml for the one-year-old and 2.38, 2.14 and 2.00 mg/100 ml for the nine-year-old ewes across all sampling times for control, CC and 25-OH-CC groups, respectively. Serum Mg in one-year-old ewes was lower (P less than .05) in both CC and 25-OH-CC injected ewes than controls, and was lowest (P less than .05) for 25-OH-CC when compared with the control in nine-year-old ewes. External symptoms of hypervitaminosis (reduced feed intake and leg abnormalities) were apparent after the second injection with 25-OH-CC, and were most pronounced in the aged ewes.

Transgenerational Transmission of the Effect of Gestational Ethanol Exposure on Ethanol Use-Related Behavior

PubMed Central

Nizhnikov, Michael E.; Popoola, Daniel O.; Cameron, Nicole M.

2018-01-01

Background Prenatal alcohol exposure (PAE) enhances the risk for alcoholism by increasing the propensity to consume alcohol and altering neurophysiological response to alcohol challenge. Transgenerationally transmittable genetic alterations have been implicated in these behavioral changes. To date, transgenerational transmission of PAE-induced behavioral responses to alcohol has never been experimentally investigated. Therefore, we explored the transgenerational transmission of PAE-induced behavioral effects across 3 generations. Methods Pregnant Sprague Dawley dams received 1 g/kg ethanol (EtOH) or water daily on gestational days 17 through 20 via gavage, or remained untreated in their home cages. To produce second filial (F2) or F3 generations, similarly treated adult F1 or F2 offspring were mated and left undisturbed through gestation. On postnatal day (PND) 14, male and female F1, F2, and F3 offspring were tested for consumption of 5% (w/v) EtOH (in water), or water. Using the loss of righting reflex (LORR) paradigm on PND 42, F1 and F2 adolescent male offspring were tested for sensitivity to acute EtOH-induced sedation–hypnosis at 3.5 or 4.5 g/kg dose. F3 male adolescents were similarly tested at 3.5 g/kg dose. Blood EtOH concentration (BEC) was measured at waking. Results EtOH exposure increased EtOH consumption compared to both water and untreated control groups in all generations. EtOH-treated group F1 and F2 adolescents displayed attenuated LORR duration compared to the water group. No attenuated LORR was observed in the F3 generation. BEC at waking corroborated with the significant LORR duration differences while also revealing differences between untreated control and water groups in F1 and F2 generations. Conclusions Our results provide novel behavioral evidence attesting that late gestational moderate EtOH exposure increases EtOH intake across 3 generations and may alter sensitivity to EtOH-induced sedation–hypnosis across 2 generations. PMID:26876534

In Vivo Anti-Inflammatory, Anti-Bacterial and Anti-Diarrhoeal Activity of Ziziphus Jujuba Fruit Extract.

PubMed

Mesaik, Ahmed M; Poh, Hiap Wei; Bin, Ooi Yan; Elawad, Izzaddinn; Alsayed, Badr

2018-05-20

Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative). To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract. The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat's treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat's paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin. EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group. EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin.

Dry-grind processing using amylase corn and superior yeast to reduce the exogenous enzyme requirements in bioethanol production.

PubMed

Kumar, Deepak; Singh, Vijay

2016-01-01

Conventional corn dry-grind ethanol production process requires exogenous alpha and glucoamylases enzymes to breakdown starch into glucose, which is fermented to ethanol by yeast. This study evaluates the potential use of new genetically engineered corn and yeast, which can eliminate or minimize the use of these external enzymes, improve the economics and process efficiencies, and simplify the process. An approach of in situ ethanol removal during fermentation was also investigated for its potential to improve the efficiency of high-solid fermentation, which can significantly reduce the downstream ethanol and co-product recovery cost. The fermentation of amylase corn (producing endogenous α-amylase) using conventional yeast and no addition of exogenous α-amylase resulted in ethanol concentration of 4.1 % higher compared to control treatment (conventional corn using exogenous α-amylase). Conventional corn processed with exogenous α-amylase and superior yeast (producing glucoamylase or GA) with no exogenous glucoamylase addition resulted in ethanol concentration similar to control treatment (conventional yeast with exogenous glucoamylase addition). Combination of amylase corn and superior yeast required only 25 % of recommended glucoamylase dose to complete fermentation and achieve ethanol concentration and yield similar to control treatment (conventional corn with exogenous α-amylase, conventional yeast with exogenous glucoamylase). Use of superior yeast with 50 % GA addition resulted in similar increases in yield for conventional or amylase corn of approximately 7 % compared to that of control treatment. Combination of amylase corn, superior yeast, and in situ ethanol removal resulted in a process that allowed complete fermentation of 40 % slurry solids with only 50 % of exogenous GA enzyme requirements and 64.6 % higher ethanol yield compared to that of conventional process. Use of amylase corn and superior yeast in the dry-grind processing industry can reduce the total external enzyme usage by more than 80 %, and combining their use with in situ removal of ethanol during fermentation allows efficient high-solid fermentation.

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet

PubMed Central

Karatayev, Olga; Lukatskaya, Olga; Moon, Sang-Ho; Guo, Wei-Ran; Chen, Dan; Algava, Diane; Abedi, Susan; Leibowitz, Sarah F.

2015-01-01

Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes an even greater vulnerability to the excessive co-use of nicotine and ethanol. PMID:25979531

Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet.

PubMed

Karatayev, Olga; Lukatskaya, Olga; Moon, Sang-Ho; Guo, Wei-Ran; Chen, Dan; Algava, Diane; Abedi, Susan; Leibowitz, Sarah F

2015-08-01

Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes an even greater vulnerability to the excessive co-use of nicotine and ethanol. Copyright © 2015 Elsevier Inc. All rights reserved.

Galanin knockout mice show disturbances in ethanol consumption and expression of hypothalamic peptides that stimulate ethanol intake

PubMed Central

Karatayev, Olga; Baylan, Jessica; Weed, Valerie; Chang, Siyi; Wynick, David; Leibowitz, Sarah F.

2009-01-01

Background There is growing evidence suggesting that hypothalamic galanin (GAL), which is known to stimulate intake of a fat-rich diet, has a role in promoting the consumption of ethanol. The present study further examined this possibility in GAL knockout (GALKO) mice. Methods Two groups of female and male GALKO mice, compared to wild-type (WT) controls, were trained to voluntarily drink increasing concentrations of ethanol, while maintained on lab chow and water. They were examined in terms of their daily ethanol intake and preference, acute consumption of a high-fat diet, preference for flavored solutions, and expression of different peptides shown to stimulate ethanol intake. Results In the GALKO mice compared to WT, the results revealed: 1) a 35-45% decrease in ethanol intake and preference, which was evident only at the highest (15%) ethanol concentration, was stronger in female than in male mice, and was seen with comparisons to littermate as well as non-littermate WT mice; 2) a 48% decrease in acute intake of a fat-rich diet, again stronger in female than male mice; 3) no difference in consumption of sucrose or quinine solutions in preference tests; 4) a total loss of GAL mRNA in the hypothalamic paraventricular nucleus (PVN) of female and male mice; and 5) a gender-specific change in mRNA levels of peptides in the perifornical lateral hypothalamus (PFLH), orexin and melanin-concentrating hormone, which are known to stimulate ethanol and food intake and were markedly decreased in females while increased in males Conclusions These results provide strong support for a physiological role of PVN GAL in stimulating the consumption of ethanol, as well as a fat-rich diet. Ablation of the GAL gene produced a behavioral phenotype, particularly in females, which may reflect the functional relationship of galanin to ovarian steroids. It also altered the peptides in the PFLH, with their reduced expression contributing to the larger behavioral effects observed in females and their increased expression attenuating these effects in males. PMID:19860804

Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol.

PubMed

Lopez, M F; Becker, H C; Chandler, L J

2014-11-01

Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of ingested ethanol on Photofrin clearance in mice

NASA Astrophysics Data System (ADS)

Montague, Donna; Fink, Louis; Stone, Angie; Flock, Stephen T.

1993-06-01

A series of experiments have been undertaken to ascertain the influence of dietary additives on the clearance of Photofrin. Post-treatment cutaneous photosensitivity continues to be a significant side effect of photodynamic therapy (PDT) in humans. Cutaneous photosensitivity in humans is evidenced by erythema and edema in exposed areas. Murine models were chosen to investigate the differences in cutaneous photosensitivity as measured by footpad thickness in the presence or absence of dietary additives. Additionally, radiation induced fibrosarcoma (RIF) cells were implanted into the subcutaneous space on the dorsal aspect of the foot. In this case, the effect of PDT on tumor growth kinetics was assumed to be proportional to Photofrin concentration. Photofrin concentrations in tumors were measured by HPLC. Serum levels for dietary additives were obtained where analytical methods were available. Ingested ethanol increased the clearance rate of Photofrin as demonstrated by measurements of Photofrin tumor concentration and by failure of RIF tumor to respond to PDT in groups treated with ethanol compared to controls.

The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats.

PubMed

Yoo, Yeong-Min; Jung, Eui-Man; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

2011-10-01

In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

Myrcia sylvatica essential oil mitigates molecular, biochemical and physiological alterations in Rhamdia quelen under different stress events associated to transport.

PubMed

Saccol, Etiane M H; Jerez-Cepa, Ismael; Ourique, Giovana M; Pês, Tanise S; Gressler, Luciane T; Mourão, Rosa H V; Martínez-Rodríguez, Gonzalo; Mancera, Juan M; Baldisserotto, Bernardo; Pavanato, Maria A; Martos-Sitcha, Juan A

2018-04-01

The effects of pre-transport handling and addition of essential oil of Myrcia sylvatica (EOMS) during transport on stress pathways activation in Rhamdia quelen were investigated. Fish (n=400, 25.2±2.9g) were captured in production ponds and transferred to 100-L tank (density 100g L -1 ). After 24h, 10 fish were sampled (before transport group). The remaining fish were placed in plastic bags (n=30 or 32 fish per bag, density 150g L -1 ) containing 5L of water (control), ethanol (315μLL -1 , vehicle) or EOMS (25 or 35μLL -1 ), in triplicate, transported for 6h and sampled (n=10 animals per group). Indicators of stress and metabolism, as well as mRNA expression of brain hormones were evaluated. Previously, full-length cDNAs, encoding specific corticotropin-releasing hormone (crh) and proopiomelanocortins (pomca and pomcb), were cloned from whole brain of R. quelen. Crh expression increased after 24h of capture and handling, whereas cortisol and glucose plasmatics enhanced their values in the control group. Transport with EOMS reduced plasma cortisol and lactate levels, while ethanol and EOMS groups increased Na + /K + -ATPase gill activity compared to control. Gene expression of crh, pomcb, prolactin and somatolactin mRNAs were lower after transport with EOMS compared to control. EOMS was able to mitigate the stress pathways activation caused by transport, maintaining a balance in body homeostasis. Thus, EOMS is recommended as sedative in procedures as transport and the pre-transport handling requires greater attention and use of tranquilizers. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of vitamin E on tracheal responsiveness and lung inflammation in sulfur mustard exposed guinea pigs.

PubMed

Boskabady, Mohammad Hossein; Amery, Sediqa; Vahedi, Nassim; Khakzad, Mohammad Reza

2011-02-01

Pulmonary complications of sulfur mustard (SM) range from mild respiratory symptoms to even severe bronchial stenosis. In the present study, the protective effect of vitamin E on tracheal responsiveness (TR) and lung inflammation of SM-exposed guinea pigs were examined. Guinea pigs were exposed to ethanol (control group), 40 mg/m(3) inhaled SM and ethanol vehicle (sulfur mustard exposed (SME) group), SME treated with vitamin E (SME + E), SME with dexamethasone (SME + D) and both drugs (SME + E + D), (n = 8 for each group). TR to methacholine, total and differential white blood cell (WBC) count of lung lavage and serum cytokines were evaluated 14 days post-exposure. TR, WBC, interleukin 4 (IL-4), interferon gamma (INF-γ), eosinophil, and monocyte levels in SME guinea pigs were significantly higher, but lymphocyte was lower than those of controls (P < 0.05 to P < 0.001). TR, IL-4, and eosinophil levels in SME + E, SME + D and SME + E + D, INF-γ in SME + E and SME + E + D and WBC in SME + E were significantly decreased compared to that of the SME group (P < 0.01 to P < 0.001). In addition, the TR of SME + D + E was significantly higher than that of SME + E (P < 0.01) and SME + D (P < 0.05) groups. The results showed a preventive effect of vitamin E, dexamethasone and their combination on TR and lung inflammation in SME guinea pigs.

Impaired TFEB-mediated Lysosome Biogenesis and Autophagy Promote Chronic Ethanol-induced Liver Injury and Steatosis in Mice.

PubMed

Chao, Xiaojuan; Wang, Shaogui; Zhao, Katrina; Li, Yuan; Williams, Jessica A; Li, Tiangang; Chavan, Hemantkumar; Krishnamurthy, Partha; He, Xi C; Li, Linheng; Ballabio, Andrea; Ni, Hong-Min; Ding, Wen-Xing

2018-05-18

Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfeb flox/flox albumin cre-negative mice (controls). TFEB was overexpressed from adenoviral vectors or knocked down with small interfering RNAs in mouse livers. Mice were placed on diets of chronic ethanol feeding plus an acute binge to induce liver damage (ethanol diet); some mice were also given injections of torin1, an inhibitor of the kinase activity of the mechanistic target of rapamycin (mTOR). Liver tissues were collected and analyzed by immunohistochemistry, immunoblots, and quantitative real-time PCR to monitor lysosome biogenesis. We analyzed levels of TFEB in liver tissues from patients with alcoholic hepatitis and from healthy donors (controls) by immunohistochemistry. Liver tissues from mice on the ethanol diet had lower levels of total and nuclear TFEB, compared with control mice, and hepatocytes had reduced lysosome biogenesis and autophagy. Hepatocytes from mice on the ethanol diet had increased translocation of mTOR into lysosomes, resulting increased mTOR activation. Administration of torin1 increased liver levels of TFEB and reduced steatosis and liver injury induced by ethanol. Mice that overexpressed TFEB in liver developed less-severe ethanol-induced liver injury and had increased lysosomal biogenesis and mitochondrial bioenergetics compared to mice carrying a control vector. Mice with knockdown of TFEB, as well as TFEB, TFE3 double-knockout mice, developed more severe liver injury in response to the ethanol diet than control mice. Liver tissues from patients with alcohol-induced hepatitis had lower nuclear levels of TFEB than control tissues CONCLUSIONS: We found chronic ethanol feeding plus an acute binge to reduce hepatic expression of the transcription factor TFEB, which is required for lysosomal biogenesis and autophagy. Strategies to block mTOR activity or increase levels of TFEB might be developed to protect liver from ethanol-induced damage. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-α (TNF-α) and endothelin-1 (ET-1).

PubMed

Du, Yong; Zhao, Weichun; Lu, Leilei; Zheng, Jiayan; Hu, Xishi; Yu, Zhehan; Zhu, Lixin

2013-12-01

To assess whether Veronicastrum axillare (V. axillare) can ameliorate ethanol-induced gastric mucosal lesions in rats, reduce the production of pro-inflammatory cytokines, suppress apoptosis and improve local microcirculation disturbances. Totally 48 male Sprague-Dawley rats were randomly divided into six groups, eight rats in each group. Rats in the normal group and the model group were administered with 0.9% normal saline respectively. Rats in the positive group and ranitidine group were administered with 0.18% ranitidine suspension by intragastric administration respectively. Those in the high dose V. axillare group, the medium dose V. axillare group and the low dose V. axillare group were administrated with V. axillare at the daily dose of 2.8 g/kg, 1.4 g/kg and 0.7 g/kg by intragastric administration. Gastric mucosal lesions were produced by intragastric administration of absolute ethanol. Water extract of V. axillare was successively injected for 14 d and last day was injected 1 h before ethanol administration. Gastric mucosal ulcer index and ulcer inhibitory rate were counted by improved Guth methods. The tissue sections were made for pathological histology analysis. Also, we measured the concentrations of tumor necrosis factor-α (TNF-α) and endothelin-1 (ET-1) in gastric mucosal, as an index of the pro-inflammatory cytokines, apoptosis and local microcirculation. Besides, the mRNA contents of TNF-α and ET-1 were measured to verify effects on gene expression by real-time fluorescent quantitative PCR. Water extract of V. axillare significantly ameliorated the gastric mucosal lesions induced by ethanol administration (P<0.01). Pro-inflammatory cytokines, TNF-α and ET-1 were increased after ethanol administration and significantly reduced by water extract of V. axillare. The expressions of TNF-α and ET-1 mRNA were also be inhibited by water extract of V. axillare. Current evidences show water extract of V. axillare is effective for defending against ethanol-induced gastric mucosal lesions, significantly inhibiting the production of pro-inflammatory cytokines and the expressions of TNF-α and ET-1 mRNA, which may be useful for inhibiting apoptosis and improving local microcirculation. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Ethanol combined with heparin as a locking solution for the prevention of catheter related blood stream infections in hemodialysis patients: A prospective randomized study.

PubMed

Sofroniadou, Sofia; Revela, Ioanna; Kouloubinis, Alexandros; Makriniotou, Ioanna; Zerbala, Sinodi; Smirloglou, Despina; Kalocheretis, Petros; Drouzas, Apostolos; Samonis, George; Iatrou, Christos

2017-10-01

Ethanol lock solution has been mainly administered in paediatric and home parenteral nutrition patients in order to prevent catheter related blood stream infections (CRBSI). Its utility in hemodialysis (HD) patients with non-tunneled-uncuffed catheter (NTC) has been poorly explored. We conducted a prospective randomized study in chronic HD patients requiring a newly inserted NTC-while awaiting for the maturation of an already established arteriovenous fistula (AVF) or arteriovenous graft (AVG) or tunneled-cuffed catheter insertion. Patients were randomized in two groups: Group A, where the lock solution was ethanol 70% + unfractionated heparin 2000 U/mL and group B, that received only unfractionated heparin 2000 U/mL. Primary end point was CRBSIs whereas exit site infections, thrombotic and bleeding episodes were the secondary end points. One hundred three HD patients were enrolled in the study (group A, n = 52; group B, n = 51). The median number of catheter days was 32 for group A (range: 23-39) and 34 (range: 27-40) for group B with no statistically significant difference between the two groups. Group A (ethanol + heparin) demonstrated 4/52 episodes (7.69%) of CRBSI whereas Group B (heparin) 11/51 episodes (21.57%) (P = 0.04). CRBSI rates per 1000 catheter days were 2.53/1000 catheter days for group A and 6.7/1000 catheter days for group B (P = 0.04). Mean cumulative infection-free catheter survival in the ethanol group did not differ significantly compared to the heparin group (log-rank test = 2.99, P = 0.08). Thrombotic episodes did not differ between the two groups. Locking of NTCs in HD patients with ethanol 70% + unfractionated heparin reduces CRBSI rates without increasing the thrombotic episodes. © 2017 International Society for Hemodialysis.

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

PubMed Central

Sunada, Katsuhisa; Shigeno, Keiji; Nakada, Akira; Honda, Michitaka; Nakamura, Tatsuo

2017-01-01

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow. PMID:29220373

Regulation of Motivation to Self-Administer Ethanol by mGluR5 in Alcohol-Preferring (P) Rats

PubMed Central

Besheer, Joyce; Faccidomo, Sara; Grondin, Julie J. M.; Hodge, Clyde W.

2008-01-01

Background Emerging evidence indicates that Group I metabotropic glutamate receptors (mGluR1 and mGluR5) differentially regulates ethanol self-administration in several rodent behavioral models. The purpose of this work was to further characterize involvement of Group I mGluRs in the reinforcing effects of ethanol using a progressive ratio schedule of reinforcement. Methods Alcohol-preferring (P) rats were trained to self-administer ethanol (15% v/v) versus water on a concurrent schedule of reinforcement, and the effects of the Group I mGluR antagonists were evaluated on progressive ratio performance. The rats were then trained to self-administer sucrose (0.4% w/v) versus water, and the effects of the antagonists were tested on progressive ratio performance. Results The mGluR1 antagonist, 3,4-dihydro-2H-pyrano[2,3]b quinolin-7-yl (cis-4-methoxy-cyclohexyl) methanone (JNJ 16259685; 0 to 1 mg/kg) and the mGluR5 antagonist, 6-methyl-2-(phenylethynyl) pyridine (MPEP; 0 to 10 mg/kg) dose-dependently reduced ethanol break point. In separate locomotor activity assessments, the lowest effective dose of JNJ 16259685 (0.3 mg/kg) produced a motor impairment, whereas the lowest effective dose of MPEP (3 mg/kg) did not. Thus, the reduction in ethanol break point by mGluR1 antagonism was probably a result of a motor impairment. JNJ 16259685 (0.3 mg/kg) and MPEP (10 mg/kg) reduced sucrose break point and produced motor impairments. Thus, the reductions in sucrose break point produced by both Group I antagonists were probably because of nonspecific effects on motor activity. Conclusions Together, these results suggest that glutamate activity at mGluR5 regulates motivation to self-administer ethanol. PMID:18162077

Effect of ethanol extract of Lepidium meyenii Walp. on osteoporosis in ovariectomized rat.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Ao, Mingzhang; Jin, Wenwen

2006-04-21

Maca (Lepidium meyenii Walp.) is a cruciferous plant from the Andes of Peru. The root of Maca is traditionally employed for its supposed properties in aphrodisiacs and improving fertility, it also has been widely used to help alleviate the symptoms of menopause. The purpose of this study was to evaluate the effect of ethanol extract of Maca on postmenopausal osteoporosis in ovariectomized rats. Female Sprague-Dawley rats were divided into four groups: Sham-operated and ovariectomized groups were fed with equivolume of distilled water, and the remaining ovariectomized groups were orally administrated with ethanol extract of Maca at 0.096 and 0.24 g/kg for 28 weeks. The findings derived from the basis of bone mineral density, biomechanical, biochemical and histopathological parameters indicated that higher dose of ethanol extract of Maca was effective in the prevention of estrogen deficient bone loss.

Embryonic Ethanol Exposure Dysregulates BMP and Notch Signaling, Leading to Persistent Atrio-Ventricular Valve Defects in Zebrafish

PubMed Central

Sarmah, Swapnalee; Muralidharan, Pooja

2016-01-01

Fetal alcohol spectrum disorder (FASD), birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs), the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3–24 hours post fertilization) led to defects in atrio-ventricular (AV) valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC). Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/β-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish. PMID:27556898

Embryonic Ethanol Exposure Dysregulates BMP and Notch Signaling, Leading to Persistent Atrio-Ventricular Valve Defects in Zebrafish.

PubMed

Sarmah, Swapnalee; Muralidharan, Pooja; Marrs, James A

2016-01-01

Fetal alcohol spectrum disorder (FASD), birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs), the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3-24 hours post fertilization) led to defects in atrio-ventricular (AV) valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC). Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/β-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish.

Chronic ethanol consumption induces erectile dysfunction: Role of oxidative stress.

PubMed

Muniz, Jaqueline J; Leite, Letícia N; De Martinis, Bruno S; Carneiro, Fernando S; Tirapelli, Carlos R

2015-11-15

Investigate the effects of chronic ethanol consumption on erectile function and on the corpus cavernosum (CC) reactivity to endothelin-1 (ET-1). Male Wistar rats were treated with ethanol (20% v/v) for six weeks. Ethanol-treated rats showed impaired erectile function represented by decreased intracavernosal pressure/mean arterial pressure (ICP/MAP) responses. Ethanol consumption increased the contractile response induced by ET-1 in the isolated CC. Tiron increased ET-1-induced contraction in CC from control and ethanol-treated rats. No differences in the maximal contraction to ET-1 were observed after incubation of CC with PEG-catalase. SC560 and SC236 increased ET-1-induced contraction in CC from ethanol-treated rats. Y27632 reduced the contraction induced by ET-1 in CC from control and ethanol-treated rats. Ethanol increased plasma TBARS, superoxide anion (O2(-)) levels and intracellular reactive oxygen species (ROS) generation in the rat CC. Reduced hydrogen peroxide (H2O2) levels in CC and increased catalase (CAT) activity in plasma and CC were detected after treatment with ethanol. Ethanol decreased superoxide dismutase (SOD) activity in the rat CC. Increased expression of COX-1 was observed in CC from ethanol-treated rats. Treatment with ethanol decreased COX-2 expression but did not alter the expression of Nox1, RhoA and p-RhoA (ser(188)) in the rat CC. The major new findings of our study are that ethanol consumption induces erectile dysfunction (ED) and increases the contraction induced by ET-1 in the rat CC by a mechanism that involves decreased generation of H2O2 and vasodilator prostanoids as well as increased activation of the RhoA/Rho-kinase pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective Effect of Camellia Oil (Camellia oleifera Abel.) against Ethanol-Induced Acute Oxidative Injury of the Gastric Mucosa in Mice.

PubMed

Tu, Pang-Shuo; Tung, Yu-Tang; Lee, Wei-Ting; Yen, Gow-Chin

2017-06-21

Camellia oil, a common edible oil in Taiwan and China, has health effects for the gastrointestinal tract in folk medicine, and it contains abundant unsaturated fatty acids and phytochemicals. However, the preventive effect of camellia oil on ethanol-induced gastric ulcers remains unclear. This study was aimed to evaluate the preventive effect of camellia oil on ethanol-induced gastric injury in vitro and in vivo as well as its mechanisms of action. In an in vitro study, our results showed that pretreatment of RGM-1 cells with camellia oil enhanced the migration ability as well as increased heat shock protein expression and reduced apoptotic protein expression. In animal experiments, mice pretreated with camellia oil effectively showed improved ethanol-induced acute injury of the gastric muscosa and oxidative damage through the enhancement of antioxidant enzyme activities and heat shock protein and PGE 2 production, as well as the suppression of lipid peroxidation, apoptosis-related proteins, pro-inflammatory cytokines, and NO production. Histological injury score and hemorrhage score in ethanol-induced gastric mucosal damage dramatically elevated from the control group (0.00 ± 0.0) to 3.40 ± 0.7 and 2.60 ± 0.5, respectively. However, treatments with camellia oil or olive oil (2 mL/kg bw) and lansoprazole (30 mg/kg bw) showed significant decreases in elevation of injury score and hemorrhage score (p < 0.05). Therefore, camellia oil has the potential to ameliorate ethanol-induced acute gastric mucosal injury through the inhibition of inflammation and oxidative stress.

Effect of Canavalia gladiata Extract Fermented with Aspergillus oryzae on the Development of Atopic Dermatitis in NC/Nga Mice.

PubMed

Kim, Ok-Kyung; Chang, Jee-Yun; Nam, Da-Eun; Park, Yoo Kyoung; Jun, Woojin; Lee, Jeongmin

2015-01-01

Canavalia gladiata has been used as a Chinese traditional folk medicine for its anti-inflammatory properties. However, the use of C. gladiata is limited because it contains antinutritional and allergy-causing proteins. We fermented C. gladiata with Aspergillus oryzae and investigated the effects of fermented C. gladiata (FCG) on the development of atopic dermatitis (AD) in mice. The mice were divided into five groups: untreated Balb/c mice; AD control (NC/Nga mice); FCGH (NC/Nga mice fed a dietary supplement of 300 mg/kg fermented C. gladiata water extract); FCG30 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 30% ethanol extract), and FCG80 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 80% ethanol extract). We found increases in the nonessential amino acids and essential amino acid in the FCG compared with the non-FCG. FCG attenuated macroscopic and histopathological changes in dorsal skin of mice when compared with the AD control group. The FCG30 and FCG80 groups, in particular, showed significant decreases in scratching episodes when compared with the AD control group. FCG improved immune responses, including increases in IgE and histamine for AD, through attenuation of Th1/Th2 cytokine imbalance and the production of proinflammatory cytokines and chemokines. We suggest that FCG may have benefits for improvement of AD function by improving the balance of Th1/Th2 cytokines and by producing anti-inflammatory effects. © 2015 S. Karger AG, Basel.

Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status.

PubMed

Ajith, T A; Hema, U; Aswathy, M S

2007-11-01

A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p<0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p<0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p<0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.

A rat model of chronic moderate alcohol consumption and risk of decompression sickness.

PubMed

Buzzacott, Peter; Mazur, Aleksandra; Wang, Qiong; Lambrechts, Kate; Theron, Michael; Guerrero, François

2015-06-01

This study aimed to establish if chronic, moderate, pre-dive alcohol consumption had any affect upon susceptibility to decompression sickness (DCS) in rats. A treatment group of 15 rats were given water containing 12 mL ·L ⁻¹ of ethanol for four weeks. Controls (n = 15) were given water. Both groups were compressed with air to 1,000 kPa, followed by staged decompression. An additional 30 control rats from a similar previous experiment were added, raising the control-treatment ratio to 3:1. Rats in the treatment group consumed the equivalent of an 80 kg man drinking 2 L of 5 % alcohol by volume beer per day, which is three times the recommended daily limit for men. Overall, comparing the treatment group with the combined control groups neither weight (P = 0.23) nor alcohol consumption (P = 0.69) were associated with DCS. We observed that chronic, moderate alcohol consumption prior to compression was neither prophylactic nor deleterious for DCS in young, male rats.

Assessment of the effects of six standard rodent diets on binge-like and voluntary ethanol consumption in male C57BL/6J mice

PubMed Central

Marshall, S. Alex; Rinker, Jennifer A.; Harrison, Langston K.; Fletcher, Craig A.; Herfel, Tina M.; Thiele, Todd E.

2015-01-01

Background In recent years much attention has been given to the lack of reproducibility in biomedical research, particularly in pre-clinical animal studies. This is a problem that also plagues the alcohol research field, particularly in consistent consumption in animal models of alcohol use disorders. One often overlooked factor that could affect reproducibility is the maintenance diet used in pre-clinical studies. Methods Herein, two well-established models of alcohol consumption, the “drinking in the dark” (DID) procedure and the continuous two-bottle choice paradigm (C2BC), were employed to determine the effects of diet on ethanol consumption. Male C57BL/6J were given one of six standard rodent-chow diets obtained from Purina LabDiet®, Inc. [St. Louis, MO; Prolab® RMH 3000] or Harlan Laboratories Inc. [Indianapolis, IN; Teklad Diets T.2916, T.2918, T.2920X, T.7912, or T.8940]. A separate group of animals were used to test dietary effects on ethanol pharmacokinetics and behavioral measures following intraperitoneal (IP) injections of various doses of ethanol. Results Mice eating Harlan diets T.2916 (H2916) and T.2920X (H2920) consumed significantly less ethanol and exhibited lower blood ethanol concentrations (BECs) during DID; however, during C2BC animals maintained on Harlan T.7912 (H7912) consumed more ethanol and had a higher ethanol preference than the other diet groups. Ethanol consumption levels did not stem from changes in alcohol pharmacokinetics, as a separate group of animals administered ethanol IP showed no difference in BECs. However, animals on Harlan diet T.2920X (H2920) were more sensitive to alcohol-induced locomotor activity in an open-field task. No diet dependent differences were seen in alcohol-induced sedation as measured with loss of righting reflex. Conclusions Although these data do not identify a specific mechanism, together they clearly show that the maintenance diet impacts ethanol consumption. It is incumbent upon the research community to consider the importance of describing nutritional information in methods, which may help decrease inter-laboratory reproducibility issues. PMID:26110576

Cytochrome P4502E1 inhibitor, chlormethiazole, decreases lipopolysaccharide-induced inflammation in rat Kupffer cells with ethanol treatment

USDA-ARS?s Scientific Manuscript database

To investigate the role of Cytochrome P4502E1 in sensitizing Kupffer cells to lipopolysaccharide (LPS)-mediated inflammation after ethanol induction. Sprague-Dawley rats were fed a liquid ethanol diet, control diet or ethanol diet supplemented with CYP2E1 inhibitor, chlormethiazole (CMZ), for 4'week...

A crucial role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through Inhibition of Wnt / Beta-catenin Signaling

USDA-ARS?s Scientific Manuscript database

The mechanisms by which chronic ethanol intake induces bone loss remain largely unclear. Especially in females, skeletal response to ethanol may vary depending on the physiologic status (viz. cycling, pregnancy, lactation). Nonetheless, ethanol-induced oxidative stress appears to be the key event le...

A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

USDA-ARS?s Scientific Manuscript database

The mechanisms by which chronic ethanol intake induces bone loss remain unclear. In females, the skeletal response to ethanol varies depending on physiologic status (viz. cycling, pregnancy, lactation). Ethanol-induced oxidative stress appears to be a key event leading to skeletal toxicity. In the c...

Strain-specific programming of prenatal ethanol exposure across generations.

PubMed

Popoola, Daniel O; Nizhnikov, Michael E; Cameron, Nicole M

2017-05-01

Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanisms. This study investigated the intergenerational consequences of prenatal exposure to a low ethanol dose (1 g/kg) during gestational days 17-20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long-Evans and Sprague-Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at a 3.5-g/kg or 4.5-g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague-Dawley rats. Lastly, we investigated PAE related changes in expression of GABA A receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague-Dawley strain. We hypothesized a reduction in the cerebral cortex GABA A receptor subunits' expression in the F1 and F2 PAE groups compared to control animals. GABA A receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE did not alter cerebral cortical GABA A receptor subunit expressions in the F1 generation, but it decreased GABA A receptor α4 and δ subunits' expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic moderate ethanol intake differentially regulates vitamin D hydroxylases gene expression in kidneys and xenografted breast cancer cells in female mice.

PubMed

García-Quiroz, Janice; García-Becerra, Rocío; Lara-Sotelo, Galia; Avila, Euclides; López, Sofía; Santos-Martínez, Nancy; Halhali, Ali; Ordaz-Rosado, David; Barrera, David; Olmos-Ortiz, Andrea; Ibarra-Sánchez, María J; Esparza-López, José; Larrea, Fernando; Díaz, Lorenza

2017-10-01

Factors affecting vitamin D metabolism may preclude anti-carcinogenic effects of its active metabolite calcitriol. Chronic ethanol consumption is an etiological factor for breast cancer that affects vitamin D metabolism; however, the mechanisms underlying this causal association have not been fully clarified. Using a murine model, we examined the effects of chronic moderate ethanol intake on tumoral and renal CYP27B1 and CYP24A1 gene expression, the enzymes involved in calcitriol synthesis and inactivation, respectively. Ethanol (5% w/v) was administered to 25-hydroxyvitamin D 3 -treated or control mice during one month. Afterwards, human breast cancer cells were xenografted and treatments continued another month. Ethanol intake decreased renal Cyp27b1 while increased tumoral CYP24A1 gene expression.Treatment with 25-hydroxyvitamin D 3 significantly stimulated CYP27B1 in tumors of non-alcohol-drinking mice, while increased both renal and tumoral CYP24A1. Coadministration of ethanol and 25-hydroxyvitamin D 3 reduced in 60% renal 25-hydroxyvitamin D 3 -dependent Cyp24a1 upregulation (P<0.05). We found 5 folds higher basal Cyp27b1 than Cyp24a1 gene expression in kidneys, whereas this relation was inverted in tumors, showing 5 folds more CYP24A1 than CYP27B1. Tumor expression of the calcitriol target cathelicidin increased only in 25-hydroxyvitamin D 3 -treated non-ethanol drinking animals (P<0.05). Mean final body weight was higher in 25-hydroxyvitamin D 3 treated groups (P<0.001). Overall, these results suggest that moderate ethanol intake decreases renal and tumoral 25-hydroxyvitamin D 3 bioconversion into calcitriol, while favors degradation of both vitamin D metabolites in breast cancer cells. The latter may partially explain why alcohol consumption is associated with vitamin D deficiency and increased breast cancer risk and progression. Copyright © 2016 Elsevier Ltd. All rights reserved.

STRAIN-SPECIFIC PROGRAMMING OF PRENATAL ETHANOL EXPOSURE ACROSS GENERATIONS

PubMed Central

Popoola, Daniel O.; Nizhnikov, Michael E.; Cameron, Nicole M.

2017-01-01

Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanism. This study investigated the intergenerational consequences of prenatal exposure to low ethanol dose (1g/kg) during gestational days 17–20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long Evans and Sprague Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at 3.5g/kg or 4.5g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits’ expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE didn’t alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor α4 and δ subunits’ expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring. PMID:28433421

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

PubMed

Thiagarajan, Venkata R K; Shanmugam, Palanichamy; Krishnan, Uma M; Muthuraman, Arunachalam

2014-08-29

The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

PubMed

Thiagarajan, Venkata R K; Shanmugam, Palanichamy; Krishnan, Uma M; Muthuraman, Arunachalam

2014-09-01

The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Effects of ethanol consumption and alcohol detoxification on the biomechanics and morphology the bone in rat femurs.

PubMed

Garcia, J A D; Souza, A L T; Cruz, L H C; Marques, P P; Camilli, J A; Nakagaki, W R; Esteves, A; Rossi-Junior, W C; Fernandes, G J M; Guerra, F D; Soares, E A

2015-11-01

The objective of this study was to verify the effects of ethanol consumption and alcohol detoxification on the biomechanics, area and thickness of cortical and trabecular bone in rat femur. This was an experimental study in which 18 male Wistar rats were used, with 40 days of age, weighing 179 ± 2.5 g. The rats were divided into three groups (n=06): CT (control), AC (chronic alcoholic), DT (detoxification). After experimental procedures, the animals were euthanized by an overdose of the anesthetic and their femurs were collected for mechanical testing and histological processing. All animals did not present malnutrition or dehydration during experimentation period. Morphometric analysis of cortical and trabecular bones in rat femurs demonstrated that AC animals showed inferior dimensions and alcohol detoxification (DT) allowed an enhancement in area and thickness of cortical and trabecular bone. Material and structural properties data of AC group highlighted the harmful effects of ethanol on bone mechanical properties. The results of this study demonstrated that chronic alcoholic rats (AC) presented major bone damage in all analyzed variables. Those findings suggested that alcohol detoxification is highly suggested in pre-operative planning and this corroborates to the success of bone surgery and bone tissue repair. Thanks to the financial support offered by PROBIC - UNIFENAS.

Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley rats

PubMed Central

Nayak, BS; Pinto Pereira, Lexley M

2006-01-01

Background Catharanthus roseus L (C. roseus) has been used to treat a wide assortment of diseases including diabetes. The objective of our study was to evaluate the antimicrobial and wound healing activity of the flower extract of Catharanthus in rats. Methods Wound healing activity was determined in rats, after administration (100 mg kg-1 day-1) of the ethanol extract of C. roseus flower, using excision, incision and dead space wounds models. The animals were divided into two groups of 6 each in all the models. In the excision model, group 1 animals were topically treated with carboxymethyl cellulose as placebo control and group 2 received topical application of the ethanol extract of C. roseus at a dose of 100 mg/kg body weight/day. In an incision and dead space model group 1 animals were given normal saline and group 2 received the extract orally at a dose of 100 mg kg-1 day-1. Healing was assessed by the rate of wound contraction, period of epithelization, tensile strength (skin breaking strength), granulation tissue weight, and hydoxyproline content. Antimicrobial activity of the flower extract against four microorganisms was also assessed Results The extract of C. roseus significantly increased the wound breaking strength in the incision wound model compared with controls (P < 0.001). The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly increased in comparison to control wounds (P < 0.001), Wet and dry granulation tissue weights, and hydroxyproline content in a dead space wound model increased significantly (p < 0.05). Pseudomonas aeruginosa and Staphylococcus aureus demonstrated sensitivity to C. roseus Conclusion Increased wound contraction and tensile strength, augmented hydroxyproline content along with antimicrobial activity support the use of C. roseus in the topical management of wound healing. PMID:17184528

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat.

PubMed

Maurel, Delphine B; Boisseau, Nathalie; Benhamou, Claude-Laurent; Jaffré, Christelle

2012-10-01

While chronic alcohol consumption is known to decrease bone mineral content (BMC), bone mineral density (BMD), and negatively modify trabecular bone microarchitecture, the impact of alcohol on cortical microarchitecture is still unclear. The aim of this study was to investigate the effects of various doses of alcohol on bone density, trabecular and cortical parameters and bone strength in rats. Forty-eight male Wistar rats were divided into four groups: control (C), alcohol 25% v/v (A25), alcohol 30% v/v (A30) and alcohol 35% v/v (A35). Rats in the alcohol groups were fed a solution composed of ethanol and water for 17 weeks while the control group drank only water. Bone quality and quantity were evaluated through the analysis of density, trabecular and cortical bone microarchitectural parameters, osteocalcin and N-Telopeptide concentrations and a 3-point bending test. Bone density along with trabecular and cortical thickness were lower in alcohol groups compared to C. BMD was lower in A35 vs. A30 and cortical thickness was lower in A35 vs. A25 and A30. Pore number was increased by alcohol and the porosity was greater in A35 compared to C. N-Telopeptide concentration was decreased in alcohol groups compared to control whereas no differences were observed in osteocalcin concentrations. Maximal energy to failure was lower in A25 and A35 compared to C. Chronic ethanol consumption increases cortical bone damage in rats and may have detrimental effects on bone strength. These effects were dose-dependent, with greater negative effects proportionate to greater alcohol doses. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.