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1

Exposure to ethanol induces oxidative damage in the pituitary gland  

Microsoft Academic Search

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone and decreased or inappropriately normal serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels suggesting a functional defect in the pituitary. The molecular mechanisms behind this disorder are undefined. A role for ethanol-induced oxidative damage in the pathophysiology is supported by studies in liver,

Jian-Ching Ren; Ali Banan; Ali Keshavarzian; Qianlong Zhu; Nancy LaPaglia; John McNulty; Nicholas V. Emanuele; Mary Ann Emanuele

2005-01-01

2

Metabolic basis of ethanol-induced hepatic and pancreatic injury in hepatic alcohol dehydrogenase deficient deer mice.  

PubMed

Alcoholic liver disease (ALD) and alcoholic pancreatitis (AP) are major diseases causing high mortality and morbidity among chronic alcohol abusers. Neutral lipid accumulation (steatosis) is an early stage of ALD or AP and progresses to inflammation and other advanced stages of diseases in a subset of chronic alcohol abusers. However, the mechanisms of alcoholic steatosis leading to ALD and AP are not well understood. Chronic alcohol abuse impairs hepatic alcohol dehydrogenase (ADH, a major enzyme involved in ethanol oxidative metabolism) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol). These esters are implicated in the pathogenesis of various alcoholic diseases and shown to cause hepatocellular and pancreatitis-like injury. Ethanol exposure is known to increase synthesis of FAEEs by several-fold in the livers and pancreata of rats pretreated with hepatic ADH inhibitor. Therefore, studies were undertaken to evaluate hepatocellular and pancreatic injury in hepatic ADH-deficient (ADH(-)) deer mice versus ADH-normal (ADH(+)) deer mice fed ethanol (4% wt/vol) via Lieber-DeCarli liquid diet for 60 days. A significant mortality was found in ethanol-fed ADH(-) deer mice (11 out of 18) versus ADH(+) deer mice (1 out of 16); most of the deaths occurred during the first 2 weeks of ethanol exposure. The surviving animals, sacrificed at the end of 60th day, showed distinct changes in hepatic and pancreatic histology and several-fold increases in nonoxidative metabolism of ethanol in ethanol-fed ADH(-) versus ADH(+) deer mice. Extensive vacuolization with displacement or absence of nucleus in some hepatocytes, and significant increase in hepatic neutral lipids were found in ethanol-fed ADH(-) versus ADH(+) deer mice. Ultrastructural changes showed perinuclear space, edema, presence of apoptotic bodies and disintegration, and/or dilatation of endoplasmic reticulum (ER) in the pancreata of ethanol-fed ADH(-) deer mice. FAEE levels were significantly higher in ADH(-) versus ADH(+) deer mice, approximately four-fold increases in the livers and seven-fold increases in the pancreata. Ethyl esters of oleic, linoleic, and arachidonic acids were the major FAEEs detected in ethanol-fed groups. The role of FAEEs in pancreatic lysosomal fragility is reflected by higher activity of cathepsin B (five-fold) in ethanol-fed ADH(-) versus ADH(+) deer mice. Although the present studies clearly indicate a metabolic basis of ethanol-induced hepatic and pancreatic injury, detailed dose- and time-dependent toxicity studies in this ADH(-) deer mouse model could reveal further a better understanding of mechanism(s) of ethanol-induced hepatic and pancreatic injuries. PMID:17127137

Bhopale, Kamlesh K; Wu, Hai; Boor, Paul J; Popov, Vsevolod L; Ansari, G A S; Kaphalia, Bhupendra S

2006-07-01

3

IL6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis: IL6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver  

Microsoft Academic Search

Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however, the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression

Osama El-Assal; Feng Hong; Won-Ho Kim; Svetlana Radaeva; Bin Gao

2004-01-01

4

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

PubMed

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. PMID:23132591

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

2012-01-01

5

The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage  

Microsoft Academic Search

The aim of this study was to assess the possible protective effects of Nigella sativa (NS) and its constituent, thymoquinone (TQ) on ethanol-induced gastric mucosal damage in an experimental model. Forty male\\u000a rats aged four months were divided into four groups (each group containing ten animals); the control group received physiologic\\u000a saline (10 ml kg?1) and the ethanol group had taken 1 ml

Mehmet Kanter; Omer Coskun; Hamdi Uysal

2006-01-01

6

Sulfated-polysaccharide fraction from red algae Gracilaria caudata protects mice gut against ethanol-induced damage.  

PubMed

The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg(-1), p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g(-1), p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg(-1), i.p.), dl-propargylglycine (PAG, 50 mg·kg(-1), p.o.) or glibenclamide (5 mg·kg(-1), i.p.). After 1 h, PLS (30 mg·kg(-1), p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25 g(-1), p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/K(ATP) pathway. PMID:22163181

Silva, Renan Oliveira; dos Santos, Geice Maria Pereira; Nicolau, Lucas Antonio Duarte; Lucetti, Larisse Tavares; Santana, Ana Paula Macedo; Chaves, Luciano de Souza; Barros, Francisco Clark Nogueira; Freitas, Ana Lúcia Ponte; Souza, Marcellus Henrique Loiola Ponte; Medeiros, Jand-Venes Rolim

2011-01-01

7

Relation of Ethanol Inhibition of Hepatic Fatty Acid Oxidation to Ethanol-Induced Fatty Liver (32641).  

National Technical Information Service (NTIS)

The quantitative importance of the inhibition of hepatic fatty acid oxidation for the pathogenesis of ethanol fatty liver has been investigated in perfused rat livers. Advantage has been taken of the fact that octanoate is poorly esterified in rat liver. ...

D. Zakim J. Green

1968-01-01

8

Inhibition of endogenous hydrogen sulfide synthesis by PAG protects against ethanol-induced gastric damage in the rat.  

PubMed

Hydrogen sulfide (H(2)S) is a gaseous mediator involved in a multitude of physiological functions; however the role of H(2)S in the gut is far from being understood completely. The aim of this study was to determine the effect of d-l-propargylglycine (PAG), an inhibitor of H(2)S synthesis, on ethanol-induced gastric injury in rat and to examine the role of l-cysteine, exogenous H(2)S, prostaglandins, non-protein sulphydryls groups, nitric oxide and K(ATP) channels in the gastroprotective effect of PAG. Administration of PAG (3.12 to 75mg/kg i.p.) or l-cysteine (0.3 to 300mg/kg, p.o.) exhibited a dose-dependent protective effect after intragastric administration of 1ml of ethanol to induce gastric injury. The gastroprotective effect of PAG (25mg/kg i.p.) was maintained after post-treatment with l-cysteine (10mg/kg p.o.), while NaHS (8.4mg/kg p.o.) inhibited this effect. The levels of gastric hydrogen sulfide were increased after ethanol-induced gastric damage and they were reverted by PAG while prostaglandin E(2) levels in gastric tissue were decreased by ethanol and PAG did not revert to this effect. Pretreatment with indomethacin (10mg/kg i.p.) and N-ethylmaleimide (NEM, 10mg/kg s.c.) resulted in a reversion of the gastroprotective effect of PAG while N(G)-nitro-l-arginine methyl ester (L-NAME, 70mg/kg s.c.), glibenclamide (1mg/kg i.p.) or diazoxide (3mg/kg i.p.) did not induce any changes. These results suggest that ethanol-induced gastric injury is related with an increment of endogenous H(2)S levels, and therefore a decrement of H(2)S levels by PAG is a benefit to protect gastric injury caused by ethanol. PMID:20035745

Chávez-Pińa, Aracely Evangelina; Tapia-Alvarez, Gabriela Rubí; Navarrete, Andrés

2010-03-25

9

Protective effect of anacardic acids from cashew (Anacardium occidentale) on ethanol-induced gastric damage in mice.  

PubMed

Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100mg/kg), misoprostol (50 microg/kg), or vehicle (2% Tween 80 in saline, 10mL/kg), 45min before ethanol administration. They were sacrificed 30min later, the stomachs excised, and the mucosal lesion area (mm(2)) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K(+)(ATP) channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation. PMID:19853593

Morais, Talita C; Pinto, Natália B; Carvalho, Karine Maria M B; Rios, Jeison B; Ricardo, Nagila Maria P S; Trevisan, Maria Teresa S; Rao, Vietla S; Santos, Flávia A

2010-01-01

10

Can megadoses of thiamine prevent ethanol induced damages of rat hippocampal CA1 pyramidal neurones?  

Microsoft Academic Search

Summary The specific aim of this study was to evaluate whether high doses of thiamine can compensate or prevent alcohol-induced damages of rat hippocampus CA1 pyramids. Twenty weeks of ethanol consumption together with a dose of thiamine in the range of 1.19 mg\\/100 mg food induced significant enlargement (parameters measured were length of the whole spine and diameter of the

S. Wenisch; T. Steinmetz; B. Fortmann; R. Leiser; I. Bitsch

1996-01-01

11

The Protective Effect of Quercetin-3-O-?-D-Glucuronopyranoside on Ethanol-induced Damage in Cultured Feline Esophageal Epithelial Cells  

PubMed Central

Quercetin-3-O-?-D-glucuronopyranoside (QGC) is a flavonoid glucoside extracted from Rumex Aquaticus Herba. We aimed to explore its protective effect against ethanol-induced cell damage and the mechanism involved in the effect in feline esophageal epithelial cells (EEC). Cell viability was tested and 2',7'-dichlorofluorescin diacetate assay was used to detect intracellular H2O2 production. Western blotting analysis was performed to investigate MAPK activation and interleukin 6 (IL-6) expression. Exposure of cells to 10% ethanol time-dependently decreased cell viability. Notably, exposure to ethanol for 30 min decreased cell viability to 43.4%. When cells were incubated with 50 µM QGC for 12 h prior to and during ethanol treatment, cell viability was increased to 65%. QGC also inhibited the H2O2 production and activation of ERK 1/2 induced by ethanol. Pretreatment of cells with the NADPH oxidase inhibitor, diphenylene iodonium, also inhibited the ethanol-induced ERK 1/2 activation. Treatment of cells with ethanol for 30 or 60 min in the absence or presence of QGC exhibited no changes in the IL-6 expression or release compared to control. Taken together, the data indicate that the cytoprotective effect of QGC against ethanol-induced cell damage may involve inhibition of ROS generation and downstream activation of the ERK 1/2 in feline EEC.

Cho, Jung Hyun; Park, Sun Young; Lee, Ho Sung; Whang, Wan Kyunn

2011-01-01

12

Biochemical and immunological basis of silymarin effect, a milk thistle (Silybum marianum) against ethanol-induced oxidative damage.  

PubMed

Ethanol metabolism induces generation of excessive amount of reactive oxygen species (ROS) which results in immune dysfunction. We examined the efficacy of silymarin on ethanol-induced oxidative stress, immunomodulatory activity, and vascular function in mice blood. Effectiveness of silymarin was compared with potent antioxidant ascorbic acid. In the present study, 8- to 10-week-old male BALB/c mice (20-30 g) were divided into the four groups of six each. One group were fed with ethanol (1.6 g/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and silybin (250 mg/kg body weight), and the third group were exposed to ethanol (250 mg/kg body weight) and ascorbic acid (250 mg/kg body weight) per day for 12 weeks. The control group was fed with isocaloric glucose solution instead of ethanol. Ethanol exposure significantly increased thiobarbituric acid reactive substance (TBARS) and nitrite levels besides glutathione-S-transferase (GST) activity, and significantly decreased reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in whole blood hemolyzate, while silymarin treatment significantly normalized these altered parameters. Silymarin significantly prevented ethanol-induced, elevated activities of interleukin (IL)-10, tumor necrosis factor (TNF)-?, ? interferon (IFN-?), vascular endothelial growth factor (VEGF)-A, and transforming growth factor (TGF)-?1, as well as decreased IL-4 activity in mice blood. These results were comparable with the activity of ascorbic acid. PMID:22409310

Das, Subir Kumar; Mukherjee, Sukhes

2012-06-01

13

Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats  

Microsoft Academic Search

Summary Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not

M. D. J. Kerai; Catherine J. Waterfield; S. H. Kenyon; D. S. Asker; J. A. Timbrell

1998-01-01

14

Effect of enprostil and cimetidine on ethanol-induced damage to intestinal epithelial cell lines IRD 98 and IEC 17.  

PubMed

In addition to their inhibitory action on gastric acid secretion, prostaglandins may exert part of their protective effect on the gastrointestinal mucosa by specifically maintaining the cellular integrity of the intestinal epithelium. This in vitro study investigated the cytoprotective effect conferred on intestinal epithelial cell lines IRD 98 and IEC 17 against ethanol injury by the synthetic prostaglandin enprostil and compared effects with those of the histamine H2-receptor blocker cimetidine. Exposure to 3% ethanol (652 mM) reduced cell viability and increased the cAMP and membrane fluidity of both cell lines. Our results demonstrate that: (i) enprostil exerts a significant cytoprotective effect against damage by ethanol; (ii) cimetidine has no cytoprotective effect; (iii) IRD 98 cells are more sensitive to enprostil than IEC 17 cells. PMID:8536822

Giannarelli, S; Nano, J L; Fournel, S; Rampal, P

1995-01-01

15

Novel role of Zn(II)-curcumin in enhancing cell proliferation and adjusting proinflammatory cytokine-mediated oxidative damage of ethanol-induced acute gastric ulcers.  

PubMed

Alcohol consumption can induce gastric ulcers and zinc deficiency. Zinc complexes were reported to have anti-ulcer activity as it acts as an anti-inflammatory and antioxidant. Zn(II)-curcumin complex and its solid dispersions (SDs) were synthesized and evaluated for its gastroprotective activity and mechanism against ethanol-induced ulcer. The Swiss murine fibroblast cell line (3T3) was used as an alternative in vitro model to evaluate the effects of Zn(II)-curcumin on cell proliferation. Zn(II)-curcumin were administered orally for seven consecutive days prior to induction of ulcers using ethanol. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that solid dispersions (SDs) of Zn(II)-curcumin (2.5-20 ?M) enhanced the proliferation of 3T3 cells more significantly than curcumin at the same concentrations (P<0.01). Oral administration of Zn(II)-curcumin (12, 24 and 48 mg/kg) SDs dose-dependently prevented formation of ulcer lesions induced by ethanol. The levels of proinflammatory cytokines tumor necrosis factor-? (TNF-?), interleukin 6 (IL-6), and oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX-Px), malonaldehyde (MDA) and H(+)-K(+)-ATPase were in the rats exposed to ethanol in ulceration have been altered. Zn(II)-curcumin prevented formation of ulcer lesions, significantly inhibited TNF-? and IL-6 mRNA expression, increased the activity of SOD and GSH-Px, reduced MDA levels and H(+)-K(+)-ATPase in mucosa of rats compared to controls (P<0.05). These findings suggest that the gastroprotective activity of Zn(II)-curcumin complex might contribute in stimulating cell proliferation and adjusting the proinflammatory cytokine-mediated oxidative damage to the gastric mucosa. PMID:22465177

Mei, Xueting; Xu, Donghui; Xu, Sika; Zheng, Yanping; Xu, Shibo

2012-04-15

16

HEPATIC DAMAGE BY RETICULOENDOTHELIAL INTERFERENCE  

Microsoft Academic Search

During an investigation of the effect of reticuloendothelial system ; (RES) interference on the incidence and growth of induced hepatic metastases of ; Walker 256 carcinoma in Sprague-Dawley rats, it was observed that blocking doses ; of India ink and Thorotrast (stabilized ThOâ) produced an increase of ; hepatic metastases associated with elevations of serum glutamic-oxalacetic (SGOT) ; and glutamic-pyruvic

E. R. Fisher; B. Fisher

1963-01-01

17

Molecular pathways underpinning ethanol-induced neurodegeneration  

PubMed Central

While genetics impacts the type and severity of damage following developmental ethanol exposure, little is currently known about the molecular pathways that mediate these effects. Traditionally, research in this area has used a candidate gene approach and evaluated effects on a gene-by-gene basis. Recent studies, however, have begun to use unbiased approaches and genetic reference populations to evaluate the roles of genotype and epigenetic modifications in phenotypic changes following developmental ethanol exposure, similar to studies that evaluated numerous alcohol-related phenotypes in adults. Here, we present work assessing the role of genetics and chromatin-based alterations in mediating ethanol-induced apoptosis in the developing nervous system. Utilizing the expanded family of BXD recombinant inbred mice, animals were exposed to ethanol at postnatal day 7 via subcutaneous injection (5.0 g/kg in 2 doses). Tissue was collected 7 h after the initial ethanol treatment and analyzed by activated caspase-3 immunostaining to visualize dying cells in the cerebral cortex and hippocampus. In parallel, the levels of two histone modifications relevant to apoptosis, ?H2AX and H3K14 acetylation, were examined in the cerebral cortex using protein blot analysis. Activated caspase-3 staining identified marked differences in cell death across brain regions between different mouse strains. Genetic analysis of ethanol susceptibility in the hippocampus led to the identification of a quantitative trait locus on chromosome 12, which mediates, at least in part, strain-specific differential vulnerability to ethanol-induced apoptosis. Furthermore, analysis of chromatin modifications in the cerebral cortex revealed a global increase in ?H2AX levels following ethanol exposure, but did not show any change in H3K14 acetylation levels. Together, these findings provide new insights into the molecular mechanisms and genetic contributions underlying ethanol-induced neurodegeneration.

Goldowitz, Dan; Lussier, Alexandre A.; Boyle, Julia K.; Wong, Kaelan; Lattimer, Scott L.; Dubose, Candis; Lu, Lu; Kobor, Michael S.; Hamre, Kristin M.

2014-01-01

18

Noninvasive Monitoring of Hepatic Damage from Hepatitis C Virus Infection  

PubMed Central

The mathematical model for the dynamics of the hepatitis C proposed in Avendańo et al. (2002), with four populations (healthy and unhealthy hepatocytes, the viral load of the hepatitis C virus, and T killer cells), is revised. Showing that the reduced model obtained by considering only the first three of these populations, known as basic model, has two possible equilibrium states: the uninfected one where viruses are not present in the individual, and the endemic one where viruses and infected cells are present. A threshold parameter (the basic reproductive virus number) is introduced, and in terms of it, the global stability of both two possible equilibrium states is established. Other central result consists in showing, by model numerical simulations, the feasibility of monitoring liver damage caused by HCV, avoiding unnecessary biopsies and the undesirable related inconveniences/imponderables to the patient; another result gives a mathematical modelling basis to recently developed techniques for the disease assessment based essentially on viral load measurements.

Alavez-Ramirez, J.; Fuentes-Allen, J. L.; Lopez-Estrada, J.

2011-01-01

19

Effects of N-acetylcysteine on ethanol-induced hepatotoxicity in rats fed via total enteral nutrition  

PubMed Central

The effects of the dietary antioxidant N-acetylcysteine (NAC) on alcoholic liver damage were examined in a total enteral nutrition (TEN) model of ethanol toxicity in which liver pathology occurs in the absence of endotoxemia. Ethanol treatment resulted in steatosis, inflammatory infiltrates, occasional foci of necrosis, and elevated ALT in the absence of increased expression of the endotoxin receptor CD14, a marker of Kupffer cell activation by LPS. In addition, ethanol treatment induced CYP2E1 and increased TNF? and TGF? mRNA expression accompanied by suppressed hepatic IL-4 mRNA expression. Ethanol treatment also resulted in the hepatic accumulation of malondialdehyde (MDA) and hydroxynonenal (HNE) protein adducts, decreased antioxidant capacity, and increased antibody titers toward serum hydroxyethyl radical (HER), MDA, and HNE adducts. NAC treatment increased cytosolic antioxidant capacity, abolished ethanol-induced lipid peroxidation, and inhibited the formation of antibodies toward HNE and HER adducts without interfering with CYP2E1 induction. NAC also decreased ethanol-induced ALT release and inflammation and prevented significant loss of hepatic GSH content. However, the improvement in necrosis score and reduction of TNF? mRNA elevation did not reach statistical significance. Although a direct correlation was observed among hepatic MDA and HNE adduct content and TNF? mRNA expression, inflammation, and necrosis scores, no correlation was observed between oxidative stress markers or TNF? and steatosis score. These data suggest that ethanol-induced oxidative stress can contribute to inflammation and liver injury even in the absence of Kupffer cell activation by endotoxemia.

Ronis, Martin J.J.; Butura, Angelica; Sampey, Brante P.; Shankar, Kartik; Prior, Ronald L.; Korourian, Sohelia; Albano, Emanuele; Ingelman-Sundberg, Magnus; Petersen, Dennis R.; Badger, Thomas M.

2010-01-01

20

Antioxidant activity and hepatoprotective potential of Hammada scoparia against ethanol-induced liver injury in rats.  

PubMed

The present work was aimed at studying the antioxidative activity and hepatoprotective effects of methanolic extract (ME) of Hammada scoparia leaves against ethanol-induced liver injury in male rats. The animals were treated daily with 35 % ethanol solution (4 g kg(-1) day(-1)) during 4 weeks. This treatment led to an increase in the lipid peroxidation, a decrease in antioxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in liver, and a considerable increase in the serum levels of aspartate and alanine aminotransferase and alkaline phospahatase. However, treatment with ME protects efficiently the hepatic function of alcoholic rats by the considerable decrease in aminotransferase contents in serum of ethanol-treated rats. The glycogen synthase kinase-3 ? was inhibited after ME administration, which leads to an enhancement of glutathione peroxidase activity in the liver and a decrease in lipid peroxidation rate by 76 %. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of ME. These results strongly suggest that treatment with methanolic extract normalizes various biochemical parameters and protects the liver against ethanol induced oxidative damage in rats. PMID:22893526

Bourogaa, Ezzeddine; Nciri, Riadh; Mezghani-Jarraya, Raoudha; Racaud-Sultan, Claire; Damak, Mohamed; El Feki, Abdelfattah

2013-06-01

21

Lithium protects ethanol-induced neuronal apoptosis  

SciTech Connect

Lithium is widely used for the treatment of bipolar disorder. Recent studies have demonstrated its neuroprotective effect. Ethanol is a potent neurotoxin that is particularly harmful to the developing nervous system. In this study, we evaluated lithium's neuroprotection against ethanol-induced apoptosis. Transient exposure of infant mice to ethanol caused apoptotic cell death in brain, which was prevented significantly by administering a low dose of lithium 15 min later. In cultured cerebellar granule neurons, ethanol-induced apoptosis and activation of caspase-3/9, both of which were prevented by lithium. However, lithium's protection is not mediated by its commonly known inhibition of glycogen synthase3{beta}, because neither ethanol nor lithium has significant effects on the phosphorylation of Akt (ser473) or GSK3{beta} (ser9). In addition, the selective GSK-3{beta} inhibitor SB-415286 was unable to prevent ethanol-induced apoptosis. These data suggest lithium may be used as a potential preventive measure for ethanol-induced neurological deficits.

Zhong Jin [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)]. E-mail: jizhong@iupui.edu; Yang Xianlin [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Yao Weiguo [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Lee Weihua [Departments of Pediatrics, Anatomy and Cell Biology, Riley Hospital for Children, 702 Barnhill Drive, Room 2641, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)

2006-12-01

22

Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway.  

PubMed

Emerging evidence has demonstrated that chronic ethanol exposure induces iron overload, enhancing ethanol-mediated liver damage. The purpose of this study was to explore the effects of the naturally occurring compound quercetin on ethanol-induced iron overload and liver damage, focusing on the signaling pathway of the iron regulatory hormone hepcidin. Adult male C57BL/6J mice were pair-fed with isocaloric-Lieber De Carli diets containing ethanol (accounting for 30% of total calories) and/or carbonyl iron (0.2%) and treated with quecertin (100 mg/kg body weight) for 15 weeks. Mouse primary hepatocytes were incubated with ethanol (100 mM) and quercetin (100 ?M) for 24 h. Mice exposed to either ethanol or iron presented significant fatty infiltration and iron deposition in the liver; these symptoms were exacerbated in mice cotreated with ethanol and iron. Quercetin attenuated the abnormity induced by ethanol and/or iron. Ethanol suppressed BMP6 and intranuclear SMAD4 as well as decreased hepcidin expression. These effects were partially alleviated by quercetin supplementation in mice and hepatocytes. Importantly, ethanol caused suppression of SMAD4 binding to the HAMP promoter and of hepcidin messenger RNA expression. These effects were exacerbated by anti-BMP6 antibody and partially alleviated by quercetin or human recombinant BMP6 in cultured hepatocytes. In contrast, co-treatment with iron and ethanol, especially exposure of iron alone, activated BMP6/SMAD4 pathway and up-regulated hepcidin expression, which was also normalized by quercetin in vivo. Quercetin prevented ethanol-induced hepatic iron overload different from what carbonyl iron diet elicited in the mechanism, by regulating hepcidin expression via the BMP6/SMAD4 signaling pathway. PMID:24746831

Tang, Yuhan; Li, Yanyan; Yu, Haiyan; Gao, Chao; Liu, Liang; Chen, Shaodan; Xing, Mingyou; Liu, Liegang; Yao, Ping

2014-06-01

23

Saponins isolated from the root of Platycodon grandiflorum protect against acute ethanol-induced hepatotoxicity in mice.  

PubMed

The protective effects of saponins isolated from the root of Platycodon grandiflorum (Changkil saponins: CKS) against alcoholic steatosis in liver injury induced by acute ethanol administration were investigated. Pretreatment with CKS prior to ethanol administration significantly prevented the increases in serum alanine aminotransferase activity, hepatic TNF-alpha level, hepatic lipid peroxidation and hepatic triglyceride level. CKS prevented ethanol-induced steatosis and necrosis, as indicated by liver histopathological studies. Additionally, CKS protected against ethanol-induced depletion of hepatic glutathione levels. CYP2E1 has been suggested as a major contributor to ethanol-induced oxidative stress and liver injury. The concurrent administration of CKS efficaciously abrogated the CYP2E1 induction and CYP2E1-dependents hydroxylation of aniline as compared to the individual treatment at higher doses. These findings suggest that CKS may prevent ethanol-induced acute liver injury, possibly through its ability to block CYP2El-mediated ethanol bioactivation and its free radical scavenging effects. PMID:19133309

Khanal, Tilak; Choi, Jae Ho; Hwang, Yong Pil; Chung, Young Chul; Jeong, Hye Gwang

2009-03-01

24

Endrin-induced increases in hepatic lipid peroxidation, membrane microviscosity, and DNA damage in rats  

Microsoft Academic Search

Endrin is a polyhalogenated cyclic hydrocarbon pesticide which produces hepatic and neurologic toxicity. Previous studies have indicated that endrin induces hepatic lipid peroxidation. In order to further assess the possible role of lipid peroxidation in the toxicity of endrin, the dose- and time-dependent effects of endrin on hepatic lipid peroxidation, membrane microviscosity and DNA damage in rats were examined. Rats

M. Bagchi; E. A. Hassoun; D. Bagchi; S. J. Stohs

1992-01-01

25

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment  

Microsoft Academic Search

Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the

Abdurrahman Karaman; Mustafa Iraz; Hale Kirimlioglu; Nese Karadag; Erkan Tas; Ersin Fadillioglu

2006-01-01

26

Antioxidant Effect of Alpha-Lipoic Acid against Ethanol-Induced Gastric Mucosal Erosion in Rats  

Microsoft Academic Search

Background\\/Aims: This investigation elucidates the role of free radicals in ethanol-induced gastric mucosal erosion and the protective effect of lipoic acid. Methods: After overnight fasting, Wistar albino rats were orally treated with 1 ml of absolute ethanol to induce gastric erosion. Lipoic acid (100 mg\\/kg) was given orally for 3 days before ethanol administration. Mucosal damage was evaluated 1 h

Meral Yüksel; Can Erzik; Sule Çetinel

2008-01-01

27

Ameliorating effects of preadolescent aniracetam treatment on prenatal ethanol-induced impairment in AMPA receptor activity  

Microsoft Academic Search

Ethanol-induced damage in the developing hippocampus may result in cognitive deficits such as those observed in fetal alcohol spectrum disorder (FASD). Cognitive deficits in FASD are partially mediated by alterations in glutamatergic synaptic transmission. Recently, we reported that synaptic transmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is impaired following fetal ethanol exposure. This finding led us to develop a rational

Nayana Wijayawardhane; Brian C. Shonesy; Thirumalini Vaithianathan; Noemi Pandiella; Julia Vaglenova; Charles R. Breese; Alexander Dityatev; Vishnu Suppiramaniam

2008-01-01

28

An early complement-dependent and TLR-4 independent phase in the pathogenesis of ethanol-induced liver injury  

PubMed Central

The innate immune system has been implicated in the pathogenesis of alcoholic liver disease. While innate immunity is usually considered an early response to injury, previous work implicating innate immunity in ethanol-induced liver injury focuses primarily on long-term ethanol exposure. Here we investigated the early period of ethanol exposure to determine whether there were temporal associations between activation of innate immune responses and known correlates of liver injury. Female C57BL/6 mice were allowed free access to an ethanol-containing Lieber-DeCarli diet or pair-fed a control diet. Within four days of ethanol exposure, we observed a striking spike in expression of hepatic pro-inflammatory cytokines, including TNF-?, IL-6 and IFN?, prior to hepatic triglyceride accumulation or increased plasma ALT activities, as well as before the induction of CYP2E1 or oxidative stress. This early spike in inflammatory cytokines coincided with deposition of C3b-iC3b/C3c (C3b) in the liver. This deposition, resulting from the cleavage of complement factor 3 (C3), is evidence for activation of complement in response to ethanol. C3?/? mice were protected from the early, ethanol-induced increase in hepatic TNF-? expression. Ethanol increased C3b deposition in mice deficient in C3a receptor or C5a receptor, as well as in wild type mice depleted of hepatic macrophages; however, there was no increase in hepatic TNF-? in the absence of C3a receptor, C5a receptor, or hepatic macrophages. In contrast, the absence of TLR-4 had no effect on the early, ethanol-induced increase in either C3b or TNF-?. In conclusion For the first time, we have identified a complement- and macrophage-dependent, but TLR-4 independent, phase in the pathogenesis of ethanol-induced liver injury.

Roychowdhury, Sanjoy; McMullen, Megan R.; Pritchard, Michele T.; Hise, Amy G.; van Rooijen, Nico; Medof, M. Edward; Stavitsky, Abram B.; Nagy, Laura E.

2009-01-01

29

Noninvasive assessment of liver damage in chronic hepatitis B  

PubMed Central

AIM: To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index (APRI) and neutrophil-lymphocyte (N/L) ratio to predict liver damage in chronic hepatitis B (CHB). METHODS: We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects. Liver biopsy materials were stained with hematoxylin-eosin and Masson’s trichrome. Patients’ fibrosis scores and histological activity index (HAI) were calculated according to the Ishak scoring system. Fibrosis score was recognized as follows: F0-1 No /early-stage fibrosis, F2-6 significant fibrosis, F0-4 non-cirrhotic and F5-6 cirrhotic. Significant liver ?brosis was de?ned as an Ishak score of ? 2. APRI and N/L ratio calculation was made by blood test results. RESULTS: The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores (P < 0.001). Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count. APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients. However, this significance was not confirmed by multiple logistic regression analysis. The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01 with sensitivity, specificity, positive predictive value and negative predictive value of 62% (36%-86%), 74% (62%-83%), 29% (13%-49%) and 92% (82%-97%), respectively. In addition, correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI (r = -0.218, P = 0.041). CONCLUSION: N/L ratio was negatively correlated with HAI. APRI score may be useful to exclude cirrhosis in CHB patients.

Celikbilek, Mehmet; Dogan, Serkan; Gursoy, Sebnem; Zarars?z, Gokmen; Yurci, Alper; Ozbak?r, Omer; Guven, Kadri; Yucesoy, Mehmet

2013-01-01

30

Mechanisms of Ethanol-induced Death of Cerebellar Granule Cells  

PubMed Central

Maternal ethanol exposure during pregnancy may cause fetal alcohol spectrum disorders (FASD). FASD is the leading cause of mental retardation. The most deleterious effect of fetal alcohol exposure is inducing neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system (CNS) underlies many of the behavioral deficits observed in FASD. The cerebellum is one of the brain areas that is most susceptible to ethanol during development. Ethanol exposure causes a loss of both cerebellar Purkinje cells and granule cells. This review focuses on the toxic effect of ethanol on cerebellar granule cells (CGC) and the underlying mechanisms. Both in vitro and in vivo studies indicate that ethanol induces apoptotic death of CGC. The vulnerability of CGC to ethanol-induced death diminishes over time as neurons mature. Several mechanisms for ethanol-induced apoptosis of CGC have been suggested. These include inhibition of NMDA receptors, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, disturbance of potassium channel currents, thiamine deficiency, and disruption of translational regulation. Cultures of CGC provide an excellent system to investigate cellular/molecular mechanisms of ethanol-induced neurodegeneration and to evaluate interventional strategies. This review will also discuss the approaches leading to neuroprotection against ethanol-induced neuroapoptosis.

Luo, Jia

2012-01-01

31

Effect of hepatic iron concentration reduction on hepatic fibrosis and damage in rats with cholestatic liver disease  

PubMed Central

AIM: To assess the effect of iron reduction after phlebotomy in rats with “normal” hepatic iron concentration (HIC) on the progression of hepatic fibrosis, as a result of bile duct ligation (BDL). METHODS: Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated. RESULTS: Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects. CONCLUSION: Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats. However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.

Peretz, Gil; Link, Gabriela; Pappo, Orit; Bruck, Rafael; Ackerman, Zvi

2006-01-01

32

The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury  

SciTech Connect

Free radical generation and catalytic iron have been implicated in the pathogenesis of alcohol-induced liver injury but the source of free radicals is a subject of controversy. The mechanism of ethanol-induced liver injury was investigated in isolated hepatocytes from a rodent model of iron loading in which free radical generation was measured by the determination of alkane production. Iron loading increased hepatic non-heme iron 3-fold, increased the prooxidant activity of cytosolic ultrafiltrates 2-fold and doubled ethanol-induced alkane production. The role of cellular oxidases as a source of ethanol induced free radicals was studied through the use of selective inhibitors. In both the presence and absence of iron loading, selective inhibition of xanthine oxidase with oxipurinol diminished ethanol-induced alkane production 0-40%, inhibition of aldehyde oxidase with menadione diminished alkane production 36-75%, while the inhibition of aldehyde and xanthine oxidase by feeding tungstate virtually abolished alkane production. Addition of acetaldehyde to hepatocytes generated alkanes at rates comparable to those achieved with ethanol indicating the importance of acetaldehyde metabolism in free radical generation.

Shaw, S.; Jayatilleke, E. (V.A. Medical Center, Bronx, NY (United States) Mount Sinai School of Medicine, New York, NY (United States))

1992-01-01

33

Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats  

PubMed Central

AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and ?-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 ± 2.81 vs 13.15 ± 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and ?-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

Birdane, Fatih Mehmet; Cemek, Mustafa; Birdane, Yavuz Osman; Gulcin, Ilhami; Buyukokuroglu, Mehmet Emin

2007-01-01

34

p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus  

NASA Astrophysics Data System (ADS)

Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G_1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein.

Puisieux, Alain; Ji, Jingwei; Guillot, Celine; Legros, Yann; Soussi, Thierry; Isselbacher, Kurt; Ozturk, Mehmet

1995-02-01

35

Differential Contributions of C3, C5 and Decay Accelerating Factor to Ethanol-induced Fatty Liver in Mice  

PubMed Central

Background & Aims: The complement pathways are important components of the innate and adaptive immune response. Here we tested the hypothesis that activation of complement is required for development of ethanol-induced fatty liver. Methods: Wild type and mice lacking the 3rd (C3) and 5th (C5) components of the complement activation pathway, as well as mice lacking decay accelerating factor (CD55/DAF), a complement regulatory protein, were fed Lieber-DeCarli ethanol-containing diets for 6 weeks or pair-fed control diets. Results: Ethanol feeding to wild type mice increased C3a in plasma. Wild type and C5-/- mice fed the ethanol diet developed hepatic steatosis characterized by micro- and macro-vesicular lipid accumulation and increased triglyceride content. C3-/- did not develop steatosis, while CD55/DAF-/- mice accumulated even more hepatic triglyceride after ethanol feeding than wild type mice. Serum ALT and hepatic TNF?, indicators of hepatocyte injury and inflammation, respectively, were increased in wild type and CD55/DAF-/- mice, but not in C5-/- mice after ethanol feeding. In contrast to the protective effect of C3-/- against ethanol-induced steatosis, both ALT and TNF? were increased in C3-/- mice after ethanol feeding. Conclusions: Here we have identified several elements of the complement system as important contributors to ethanol-induced fatty liver. C3 contributed primarily to the accumulation of triglyceride in the liver, while C5 was involved in inflammation and injury to hepatocytes. Further, the absence of CD55/DAF exacerbated these responses, suggesting that CD55/DAF serves as a barrier to ethanol-induced fatty liver.

Stavitsky, Abram B.; Cohen, Jessica I.; Nagy, Laura E.

2006-01-01

36

Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery  

PubMed Central

AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepatobiliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arterial collaterals to the liver which may affect post-TAE liver damage and patient outcome. RESULTS: The underlying diseases were all malignancies, and the surgical procedures included hepatopancreatoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenectomy in 2. A total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful hemostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arterial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic artery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral pathways to the liver created by the primary surgical procedure and a short postoperative interval may lead to an unfavorable outcome.

Tajima, Yoshitsugu; Kuroki, Tamotsu; Tsutsumi, Ryuji; Sakamoto, Ichiro; Uetani, Masataka; Kanematsu, Takashi

2007-01-01

37

Protective role of Phyllanthus niruri against nimesulide induced hepatic damage  

Microsoft Academic Search

Present study aimed to evaluate the protective role of the aqueous extract of Phyllanthus niruri (P. niruri) against nimesulide-induced\\u000a hepatic disoder in mice by determining levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase\\u000a (GPT) and alkaline phosphatase (ALP) in serum and also by measuring the hepatic content of the antioxidant enzymes, superoxide\\u000a dismitase (SOD) and catalase (CAT); the free

Mary Chatterjee; Parames C. Sil

2007-01-01

38

Effect of tauroursodeoxycholic and ursodeoxycholic acid on ethanol-induced cell injuries in the human Hep G2 cell line  

Microsoft Academic Search

Background & Aims: Taurodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) exert a protective effect in chronic cholestasis. This study reports the effect of TUDCA and UDCA on an in vitro model for ethanol-induced liver damage. Methods: Hep G2 cells were incubated for 24 hours with 80 mmol\\/L ethanol in the presence or absence of 50 ?mol\\/L TUDCA or UDCA. Cells

Manuela G. Neuman; Ross G. Cameron; Neil H. Shear; Stefano Bellentani; Claudio Tiribelli

1995-01-01

39

ETHANOL-INDUCED LOCOMOTOR ACTIVITY IN ADOLESCENT RATS AND THE RELATIONSHIP WITH ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE AND CONDITIONED TASTE AVERSION  

PubMed Central

Adolescent rats exhibit ethanol-induced locomotor activity (LMA), which is considered an index of ethanol’s motivational properties likely to predict ethanol self-administration, but few studies have reported or correlated ethanol-induced LMA with conditioned place preference by ethanol at this age. The present study assessed age-related differences in ethanol’s motor stimulating effects and analysed the association between ethanol-induced LMA and conventional measures of ethanol-induced reinforcement. Experiment 1 compared ethanol-induced LMA in adolescent and adult rats. Subsequent experiments analyzed ethanol-induced conditioned place preference and conditioned taste aversion in adolescent rats evaluated for ethanol-induced LMA. Adolescent rats exhibit a robust LMA after high-dose ethanol. Ethanol-induced LMA was fairly similar across adolescents and adults. As expected, adolescents were sensitive to ethanol’s aversive reinforcement, but they also exhibited conditioned place preference. These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA.

Acevedo, Maria Belen; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.; Pautassi, Ricardo Marcos

2012-01-01

40

Depletion of Kupffer cells modulates ethanol-induced hepatocyte DNA synthesis in C57Bl/6 mice.  

PubMed

Kupffer cells (KCs) are important in hepatic homeostasis and responses to xenobiotics. KCs are activated on interaction with endotoxin, releasing cytokines, and reactive oxygen species normally associated with increased gene expression, cellular growth, or hepatic injury. Ethanol-induced endotoxemia is one means of KC activation. We propose that KC depletion attenuates the effect of EtOH-induced endotoxemia to impact the hepatic growth response. Hepatic DNA synthesis was examined in KC competent (KC+) or KC-depleted (KC-) C57BL/6 mice fed EtOH-containing diet in the presence or absence of polyphenol-60 antioxidant. KC depletion was assessed by F4/80 antigen, and DNA synthesis was assessed by 5-bromo-2'-deoxyuridine incorporation. Tumor necrosis factor alpha (TNF-?) messenger RNA released was quantified by RT-PCR/electrophoresis. ERK1/2 phosphorylation was evaluated by Western blotting, and Nrf2 and CYP2E1protein were also assayed. Apoptosis and hepatic injury were examined by the Tunnel assay and hepatic transaminases in serum, respectively. Hepatic transaminases in serum (AST and ALT) were within normal range. Over 90% of KC was depleted by clodronate treatment. KC depletion decreased TNF-? mRNA release, ERK1/2 phosphorylation, and hepatocyte DNA synthesis. KC depletion is associated with increased numbers of apoptotic cells bodies in KC- mice. Antioxidant treatment decreased DNA synthesis, Nrf2, and CYP2E1 protein expression in EtOH-consuming mice. Our data indicate that upon ethanol exposure, KC participates in hepatic DNA synthesis and growth responses. Collectively, these observations suggest that KC depletion attenuates the downstream effect of ethanol-induced endotoxemia by reduced cytokine and reactive oxygen species production with its concomitant effect on MAPK-signaling pathway on hepatocyte DNA synthesis. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 867-875, 2014. PMID:22996800

Owumi, Solomon E; Corthals, Stacy M; Uwaifo, Anthony O; Kamendulis, Lisa M; Klaunig, James E

2014-08-01

41

Perillyl alcohol protects against ethanol induced acute liver injury in Wistar rats by inhibiting oxidative stress, NF?-B activation and proinflammatory cytokine production  

Microsoft Academic Search

Oxidative stress and inflammation are two major etiological factors that are suggested to play key roles in the development of ethanol induced liver injury. Release of proinflammatory cytokine like tumor necrosis factor alpha (TNF-?) and activation of nuclear factor kappa-B (NF?-B) may strongly intensify inflammation and cell damage. Additionally, reactive oxygen species (ROS) also exerts significant effect in this whole

Abdul Quaiyoom Khan; Sana Nafees; Sarwat Sultana

2011-01-01

42

Antihepatotoxic effect of Nymphaea stellata willd., against carbon tetrachloride-induced hepatic damage in albino rats  

Microsoft Academic Search

Nymphaea stellata willd., a medicinal plant mentioned in Ayurveda for the treatment of liver disorders, has not been subjected to systematic scientific investigations to asses its hepatoprotective effects. Therefore, the present study was undertaken to investigate the hepatoprotective activity of extract of Nymphaea stellata willd., flower against carbon tetrachloride-induced hepatic damage in albino rats. The oral administration of varying dosage

Manoj R Bhandarkar; Aqueel Khan

2004-01-01

43

Role of Complement in Ethanol-Induced Liver Injury  

Microsoft Academic Search

\\u000a The complement cascade is a phylogenetically ancient part of our immune system and is critical to an organism’s ability to\\u000a ward off infection. Interest in a possible role for the complement system in the development of ethanol-induced liver injury\\u000a was inspired by the large body of data implicating the complement system in the development of acute and chronic inflammatory\\u000a responses

Michele T. Pritchard; Megan R. McMullen; M. Edward Medof; Abram Stavitsky; Laura E. Nagy

44

AMPA receptor potentiation can prevent ethanol-induced intoxication.  

PubMed

We present a substantial series of behavioral and imaging experiments, which demonstrate, for the first time, that increasing AMPA receptor-mediated neurotransmission via administration of potent and selective biarylsulfonamide AMPA potentiators LY404187 and LY451395 reverses the central effects of an acutely intoxicating dose of ethanol in the rat. Using pharmacological magnetic resonance imaging (phMRI), we observed that LY404187 attenuated ethanol-induced reductions in blood oxygenation level dependent (BOLD) in the anesthetized rat brain. A similar attenuation was apparent when measuring local cerebral glucose utilization (LCGU) via C14-2-deoxyglucose autoradiography in freely moving conscious rats. Both LY404187 and LY451395 significantly and dose-dependently reversed ethanol-induced deficits in both motor coordination and disruptions in an operant task where animals were trained to press a lever for food reward. Both prophylactic and acute intervention treatment with LY404187 reversed ethanol-induced deficits in motor coordination. Given that LY451395 and related AMPA receptor potentiators/ampakines are tolerated in both healthy volunteers and elderly patients, these data suggest that such compounds may form a potential management strategy for acute alcohol intoxication. PMID:17851540

Jones, Nicholas; Messenger, Marcus J; O'Neill, Michael J; Oldershaw, Anna; Gilmour, Gary; Simmons, Rosa M A; Iyengar, Smriti; Libri, Vincenzo; Tricklebank, Mark; Williams, Steve C R

2008-06-01

45

Metadoxine prevents damage produced by ethanol and acetaldehyde in hepatocyte and hepatic stellate cells in culture.  

PubMed

Metadoxine (pyridoxine-pyrrolidone carboxylate) has been reported to improve liver function tests in alcoholic patients. In the present work we have investigated the effect of metadoxine on some parameters of cellular damage in hepatocytes and hepatic stellate cells in culture treated with ethanol and acetaldehyde. HepG2 and CFSC-2G cells were treated with 50 mM ethanol or 175 microM acetaldehyde as initial concentration in the presence or absence of 10 microg ml(-1) of metadoxine. Twenty-four hours later reduced and oxidized glutathione content, lipid peroxidation damage, collagen secretion and IL-6, IL-8 and TNF- alpha secretion were determined. Our results suggest that metadoxine prevents glutathione depletion and the increase in lipid peroxidation damage caused by ethanol and acetaldehyde in HepG2 cells. In hepatic stellate cells, metadoxine prevents the increase in collagen and attenuated TNF- alpha secretion caused by acetaldehyde. Thus, metadoxine could be useful in preventing the damage produced in early stages of alcoholic liver disease as it prevents the redox imbalance of the hepatocytes and prevents TNF- alpha induction, one of the earliest events in hepatic damage. PMID:11712874

Gutiérrez-Ruiz, M C; Bucio, L; Correa, A; Souza, V; Hernández, E; Gómez-Quiroz, L E; Kershenobich, D

2001-11-01

46

Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats.  

PubMed

Purified oleuropein from olive leaf extract has been shown to have antioxidant effects in our recent studies. Thus, the aim of this study was to assess the antioxidant abilities of oleuropein in comparison with ranitidine in ethanol-induced gastric damages via evaluation of ulcer index inhibition, antioxidant enzyme activities, and lipid peroxidation level. Fifty-six adult male Sprague-Dawley rats were divided into seven equal groups as follows: control group, ethanol group (absolute ethanol 1 ml/rat), oleuropein group (12 mg/kg), and oleuropein (6, 12, and 18 mg/kg) plus ethanol groups, as well as ranitidine (50 mg/kg) plus ethanol group. Pretreatment with oleuropein (12 and 18 mg/kg) significantly increased the ulcer index inhibition (percent), in comparison with oleuropein (6 mg/kg). Glutathione peroxidase (GPx) activity was significantly lower in the ethanol group when compared with the other groups whereas, treatment of rats with oleuropein (12 mg/kg) significantly increased glutathione content in gastric tissue when compared with the other groups, and lipid peroxidation was significantly reduced in the oleuropein- (12 and 18 mg/kg) and ranitidine-treated animals. Superoxide dismutase (SOD) and catalase (CAT) activities were both much higher in oleuropein-treated rats than the ethanol group, and although there was a moderate increase in SOD and CAT activities in ranitidine-treated rats, the differences were not significant. These findings suggest that oleuropein has beneficial antioxidant properties against ethanol-induced gastric damages in the rat. Therefore, it seems that a combination regimen including both antioxidant and antisecretory drugs may be beneficial in prevention of ethanol-mediated gastric mucosal damages. PMID:22581435

Alirezaei, Masoud; Dezfoulian, Omid; Neamati, Shima; Rashidipour, Marzyeh; Tanideh, Nader; Kheradmand, Arash

2012-12-01

47

Sulforaphane protects against ethanol-induced oxidative stress and apoptosis in neural crest cells by the induction of Nrf2-mediated antioxidant response  

PubMed Central

Background and Purpose Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that up-regulates a diverse array of antioxidant genes and protects cells from oxidative damage. This study is designed to determine whether D-L-sulforaphane (SFN) can protect neural crest cells (NCCs), an ethanol-sensitive cell population implicated in fetal alcohol spectrum disorders, against ethanol-induced apoptosis and whether protective effects of SFN are mediated by the induction of Nrf2-mediated antioxidant response. Experimental Approach Control, SFN-treated or Nrf2-siRNA transfected NCCs were exposed to ethanol. Nrf2 activation, the expression and activities of Nrf2 downstream antioxidant proteins, reactive oxygen species generation and apoptosis were determined in control and ethanol-exposed NCCs. Key Results Exposure of NCCs to SFN alone significantly increased Nrf2 activation and the expression of Nrf2 downstream antioxidants as well as the activities of the antioxidant enzymes. Treatment of NCCs with SFN along with ethanol significantly decreased ethanol-induced oxidative stress and apoptosis. In contrast, knockdown of Nrf2 by siRNA significantly increased the sensitivity of NCCs to ethanol-induced oxidative stress and apoptosis. Suppression of Nrf2 signalling in NCCs also significantly diminished SFN-mediated antioxidant response and abolished the protective effects of SFN on ethanol-induced oxidative stress and apoptosis. Conclusions and Implications These results demonstrated that Nrf2-mediated antioxidant response plays an important role in the susceptibility of NCCs to ethanol-induced oxidative stress and apoptosis and that the protection of SFN against ethanol-induced oxidative stress and apoptosis in NCCs is mediated by the induction of Nrf2 signalling.

Chen, X; Liu, J; Chen, S-Y

2013-01-01

48

Protective Effects of Emodin and Chrysophanol Isolated from Marine Fungus Aspergillus sp. on Ethanol-Induced Toxicity in HepG2/CYP2E1 Cells  

PubMed Central

Alcohol-induced liver injury progresses from fatty infiltration followed by a harmful cause of inflammation leading to an irreversible damage. In this study, two compounds (emodin and chrysophanol) isolated from marine fungus Aspergillus sp. were examined for their protective effects against ethanol-induced toxicity in vitro. Ethanol-induced HepG2/CYP2E1 cells were treated with the compounds at various concentrations, and the results showed that there was a dose-dependent decrease of gamma-glutamyl transpeptidase (GGT) activity and increase of glutathione (GSH) in the culture media with an increase in cell viability. Furthermore, the protective effects of the compounds were evaluated by protein expression levels of GGT, GSH, and CYP2E1 using Western blot. Among the compounds, emodin addressed to the ethanol-induced cytotoxicity more effectively compared to the chrysophanol. It could be suggested that emodin isolated from this genus would be a potential candidate for attenuating ethanol induced liver damage for further industrial applications such as functional food and pharmaceutical developments.

Qian, Zhong-Ji; Zhang, Chen; Li, Yong-Xin; Je, Jae-Young; Kim, Se-Kwon; Jung, Won-Kyo

2011-01-01

49

Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats.  

PubMed

We investigated the effects of silymarin and naringenin in counteracting arsenic-induced hepatic oxidative stress post exposure. Male wistar rats were chronically exposed to sodium arsenite for eight months followed by oral treatment with silymarin and naringenin (50 mg/kg each) for 15 consecutive days to evaluate hepatic damage and antioxidant potential. Our results demonstrate a significant decrease in hepatic GSH levels, SOD and catalase activities and an increase in GST and TBARS levels after arsenic administration. Silymarin or naringenin administration increased GSH levels and was beneficial in the recovery of altered SOD and catalase activity besides significantly reducing blood and tissue arsenic concentration. Our results point to the antioxidant potential of these flavonoids, which might be of benefit in the clinical recovery of subject exposed to arsenic. These flavonoids can be incorporated into the diet or co-supplemented during chelation treatment, and thus may afford a protective effect against arsenite-induced cytotoxicity. PMID:20719385

Jain, Anshu; Yadav, Abhishek; Bozhkov, A I; Padalko, V I; Flora, S J S

2011-05-01

50

Focal cortical damage parallels cognitive impairment in minimal hepatic encephalopathy.  

PubMed

Little attention has been paid to cortical integrity in patients with minimal hepatic encephalopathy (MHE), although cognitive functions affected in early stages of liver disease are mainly allocated in different neocortical structures. Here we used cortical surface-based analysis techniques to investigate if patterns of cortical thinning accompany the mildest form of HE. To aim this goal, cortical thickness obtained from high-resolution 3T magnetic resonance imaging (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls. Further correlation analyses were performed to examine whether scores in the critical flicker frequency (CFF) test, and blood ammonia levels accounted for the loss of cortical integrity in different stages of liver disease. Finally, we assessed group differences in volume of different subcortical regions and their potential relationships with CFF scores/blood ammonia levels. Results showed a focal thinning of the superior temporal cortex and precuneus in MHE patients when compared with NMHE and controls. Relationships between blood ammonia levels and cortical thickness of the calcarine sulcus accounted for impaired visual judgment in patients with MHE when compared to NMHE. Regression analyses between cortical thickness and CFF predicted differences between controls and the two groups of HE patients, but failed to discriminate between patients with NMHE and MHE. Taking together, these findings provide the first report of cortical thinning in MHE patients, and they yield novel insights into the neurobiological basis of cognitive impairment associated with early stages of liver diseases. PMID:22465844

Montoliu, Carmina; Gonzalez-Escamilla, Gabriel; Atienza, Mercedes; Urios, Amparo; Gonzalez, Olga; Wassel, Abdallah; Aliaga, Roberto; Giner-Duran, Remedios; Serra, Miguel A; Rodrigo, Jose M; Belloch, Vicente; Felipo, Vicente; Cantero, Jose L

2012-07-16

51

Hepatotherapeutic effect of Aloe vera in alcohol-induced hepatic damage.  

PubMed

There is a lack of reliable hepatotherapeutic drugs in modern medicine in the management of alcohol/drug-induced liver damage. Aloe vera extract has been used in folklore medicine for its medicinal values. This study evaluates the hepatotherapeutic activity of aqueous extract of Aloe vera gel in rats. Sprague-Dawley rats were divided into three groups; the negative control, positive control and the extract-treated groups. The negative control received only distilled water daily. The positive control received alcohol, while the extract-treated group received aqueous extract of Aloe vera and alcohol. Hepatotoxicity was induced in the positive control and extract-treated rats with alcohol. The hepatotherapeutic effect was evaluated by performing an assay of the serum total bilirubin, alkaline phosphatase, aspartate and alanine transaminases and liver histopathology. Alanine transaminase activities were comparable in all groups. Alcohol treatment alone significantly (p < 0.05) increased total serum bilirubin, alkaline phosphatase and aspartate transaminase activities. Alcohol-induced hepatic dysfunction was abrogated by Aloe vera extract. Histopathological examination revealed that alcohol induced hepatic damage. Aloe vera treatment maintained hepatic architecture similar to that seen in the control. This study shows that aqueous extract of Aloe vera gel is hepatotherapeutic and thus lends credence to the use of the plant in folklore medicine in the management of alcohol-induced hepatic dysfunction. PMID:22308658

Saka, W A; Akhigbe, R E; Ishola, O S; Ashamu, E A; Olayemi, O T; Adeleke, G E

2011-07-15

52

Circulating Cytokines and Histological Liver Damage in Chronic Hepatitis B Infection  

PubMed Central

Each phase of hepatitis B infection stimulates distinct viral kinetics and host immune responses resulting in liver damage and hepatic fibrosis. Our objective has been to correlate host inflammatory immune response including circulating Th1 and Th2 cytokines in patients with chronic hepatitis B infection with liver histopathology. Sixty-four patients with chronic hepatitis B without previous treatment were recruited. The liver histology and histological activity index were assessed for various degrees of necroinflammation and hepatic fibrosis. We determined circulating levels of the Th1 and Th2 cytokines. Forty-six males and 18 females at a median age of 34.5 years were studied. HBeAg was present in 28/64 (43.75%) of the patients. In patients negative for HBeAg, IL-10 and IFN-gamma were significantly correlated with degrees of necroinflammation (r = 0.34, r = 0.38, resp.; P < 0.05). Moreover, TNF-alpha was significantly correlated with degrees of fibrosis (r = 0.35; P < 0.05), and IL-10 and TNF-alpha were significantly correlated with significant fibrosis (r = 0.39, r = 0.35, resp.; P < 0.05). These correlations were found in the HBeAg negative group as opposed to the HBeAg positive group. In HBeAg negative patients, circulating cytokines IL-10 and IFN-gamma were correlated with degrees of necroinflammation, whereas IL-10 and TNF-alpha were correlated with significant fibrosis.

Tangkijvanich, Pisit; Chirathaworn, Chintana; Wisedopas, Naruemon; Treeprasertsuk, Sombat; Komolmit, Piyawat; Poovorawan, Yong

2013-01-01

53

Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats  

PubMed Central

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-?, and tumor necrosis factor (TNF)-?. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-?, and IL-1? in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-?, and IL-1?, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo.

Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha

2013-01-01

54

Adenosine signaling contributes to ethanol-induced fatty liver in mice  

PubMed Central

Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the biochemical and pharmacological mechanisms by which ethanol stimulates these molecular changes remain unknown. During ethanol metabolism, adenosine is generated by the enzyme ecto-5?-nucleotidase, and adenosine production and adenosine receptor activation are known to play critical roles in the development of hepatic fibrosis. We therefore investigated whether adenosine and its receptors play a role in the development of alcohol-induced fatty liver. WT mice fed ethanol on the Lieber-DeCarli diet developed hepatic steatosis, including increased hepatic triglyceride content, while mice lacking ecto-5?-nucleotidase or adenosine A1 or A2B receptors were protected from developing fatty liver. Similar protection was also seen in WT mice treated with either an adenosine A1 or A2B receptor antagonist. Steatotic livers demonstrated increased expression of genes involved in fatty acid synthesis, which was prevented by blockade of adenosine A1 receptors, and decreased expression of genes involved in fatty acid metabolism, which was prevented by blockade of adenosine A2B receptors. In vitro studies supported roles for adenosine A1 receptors in promoting fatty acid synthesis and for A2B receptors in decreasing fatty acid metabolism. These results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A1 and A2B receptors and suggest that targeting adenosine receptors may be effective in the prevention of alcohol-induced fatty liver.

Peng, Zhongsheng; Borea, Pier Andrea; Wilder, Tuere; Yee, Herman; Chiriboga, Luis; Blackburn, Michael R.; Azzena, Gianfranco; Resta, Giuseppe; Cronstein, Bruce N.

2009-01-01

55

Ulcerative colitis-induced hepatic damage in mice: studies on inflammation, fibrosis, oxidative DNA damage and GST-P expression.  

PubMed

There exists a close relationship between ulcerative colitis and various hepatic disorders. The present study was aimed to evaluate the hepatocellular damage in experimental colitis model. Ulcerative colitis was induced in Swiss mice by cyclic treatment with 3% w/v dextran sulfate sodium in drinking water. The severity of colitis was assessed on the basis of disease activity index and colon histology. The effect of ulcerative colitis on the liver was assessed using various biochemical parameters, histological evaluation, sirius red staining, immunohistochemical staining with peroxisome proliferator-activated receptor ?, 8-oxo-7,8-dihydro-2'-deoxyguanosine and placental glutathione S-transferase, comet assay (alkaline and modified), Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assay and western blot analysis to detect the protein expression of nuclear factor kappa B, cyclooxygenase-2, nuclear erythroid 2-related factor 2 and NADPH: quinone oxidoreductase-1. Dextran sulfate sodium induced severe colitis in mice as evident from an elevated disease activity index and histological abnormalities. Ulcerative colitis increased the permeability of colon as apparent from a significant reduction in the expression of tight junction protein, occludin. Further, the bacterial translocation assay as well as the analysis of lipopolysaccharide level revealed the existence of various bacterial species in the liver of ulcerative colitis-induced mice. There was a significant increase in the plasma alanine and aspartate transaminases and liver triglyceride levels, expression of peroxisome proliferator-activated receptor ?, inflammatory markers, oxidative stress, fibrosis, oxidative DNA damage and apoptosis in the liver of mice. Moreover, there was an increase in the expression of nuclear factor kappa B and cyclooxygenase-2 and a reduction in the expression of nuclear erythroid 2-related factor 2 and NADPH: quinone oxidoreductase-1 in the liver of severe ulcerative colitis-induced mice. The results of the present study provide evidence that ulcerative colitis is accompanied with hepatic damage in mice. PMID:23261717

Trivedi, P P; Jena, G B

2013-01-25

56

Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons  

PubMed Central

Background Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met) and thymoquinone (TQ) during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD) 17.5. Results We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM) exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (??M), which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2), increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death. Conclusion These findings suggested that Met and TQ are strong protective agents against ethanol-induced neuronal apoptosis in primary rat cortical neurons. The collective data demonstrated that Met and TQ have the potential to ameliorate ethanol neurotoxicity and revealed a possible protective target mechanism for the damaging effects of ethanol during early brain development.

2012-01-01

57

Alcohol oxidizing enzymes and ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells.  

PubMed

Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disease causing significant morbidity and mortality. Due to lack of a suitable animal model, the underlying mechanism of ACP is poorly understood. Chronic alcohol abuse inhibits alcohol dehydrogenase (ADH) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs) in the pancreas frequently damaged during chronic ethanol abuse. Earlier, we reported a concentration-dependent formation of FAEEs and cytotoxicity in ethanol-treated rat pancreatic tumor (AR42J) cells, which express high FAEE synthase activity as compared to ADH and cytochrome P450 2E1. Therefore, the present study was undertaken to investigate the role of various ethanol oxidizing enzymes in ethanol-induced pancreatic acinar cell injury. Confluent AR42J cells were pre-treated with inhibitors of ADH class I and II [4-methylpyrazole (MP)] or class I, II, and III [1,10-phenanthroline (PT)], cytochrome P450 2E1 (trans-1,2-dichloroethylene) or catalase (sodium azide) followed by incubation with 800 mg% ethanol at 37°C for 6 h. Ethanol metabolism, cell viability, cytotoxicity (apoptosis and necrosis), cell proliferation status, and formation of FAEEs in AR42J cells were measured. The cell viability and cell proliferation rate were significantly reduced in cells pretreated with 1,10-PT + ethanol followed by those with 4-MP + ethanol. In situ formation of FAEEs was twofold greater in cells incubated with 1,10-PT + ethanol and ?1.5-fold in those treated with 4-MP + ethanol vs. respective controls. However, cells treated with inhibitors of cytochrome P450 2E1 or catalase in combination of ethanol showed no significant changes either for FAEE formation, cell death or proliferation rate. Therefore, an impaired ADH class I-III catalyzed oxidation of ethanol appears to be a key contributing factor in ethanol-induced pancreatic injury via formation of nonoxidative metabolites of ethanol. PMID:24281792

Bhopale, Kamlesh K; Falzon, Miriam; Ansari, G A S; Kaphalia, Bhupendra S

2014-04-01

58

Role of Nrf2 in preventing ethanol-induced oxidative stress and lipid accumulation  

SciTech Connect

Oxidative stress and lipid accumulation play important roles in alcohol-induced liver injury. Previous reports showed that, in livers of nuclear factor erythroid 2-related factor 2 (Nrf2)-activated mice, genes involved in antioxidant defense are induced, whereas genes involved in lipid biosynthesis are suppressed. To investigate the role of Nrf2 in ethanol-induced hepatic alterations, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation, were treated with ethanol (5 g/kg, po). Blood and liver samples were collected 6 h thereafter. Ethanol increased alanine aminotransferase and lactate dehydrogenase activities as well as thiobarbituric acid reactive substances in serum of Nrf2-null and wild-type mice, but not in Nrf2-enhanced mice. After ethanol administration, mitochondrial glutathione concentrations decreased markedly in Nrf2-null mice but not in Nrf2-enhanced mice. H{sub 2}DCFDA staining of primary hepatocytes isolated from the four genotypes of mice indicates that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. Ethanol increased serum triglycerides and hepatic free fatty acids in Nrf2-null mice, and these increases were blunted in Nrf2-enhanced mice. In addition, the basal mRNA and nuclear protein levels of sterol regulatory element-binding protein 1(Srebp-1) were decreased with graded Nrf2 activation. Ethanol further induced Srebp-1 mRNA in Nrf2-null mice but not in Nrf2-enhanced mice. In conclusion, Nrf2 activation prevented alcohol-induced oxidative stress and accumulation of free fatty acids in liver by increasing genes involved in antioxidant defense and decreasing genes involved in lipogenesis. -- Highlights: ? Ethanol depleted mitochondrial GSH in Nrf2-null mice but not in Keap1-KD mice. ? Ethanol increased ROS in hepatocytes isolated from Nrf2-null and wild-type mice. ? Nrf2 blunted ethanol-induced increase of triglycerides and free fatty acids. ? The mRNA and nuclear protein of Srebp-1 were decreased with Nrf2 activation. ? The mRNA of Scd1 was increased in Nrf2-null mice after ethanol exposure.

Wu, Kai Connie [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)] [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)] [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

2012-08-01

59

Hepatoprotective and antioxidant activity of linden (Tilia platyphyllos L.) infusion against ethanol-induced oxidative stress in rats.  

PubMed

The present study was carried out to evaluate the hepatoprotective effect and antioxidant role of infusion prepared from linden flowers (LF) against ethanol-induced oxidative stress. The hepatoprotective and antioxidant role of the plant's infusion against ethanol-induced oxidative stress was evaluated by measuring liver damage serum biomarkers, aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase (LDH), total protein, total albumin, and total cholesterol level; ADS such as GSH, GR, SOD, GST, CAT and GPx, and MDA contents in various tissues of rats. Rats were divided into four experimental groups: I (control), II (20 % ethanol), III (2 % LF), and IV (20 % ethanol + 2 % LF). According to the results, the level of serum marker enzymes, AST and LDH, was significantly increased in group alcohol and group LF as compared to control group, whereas decreased in group IV as compared to ethanol group. With regard to MDA content and ADS constituents, MDA contents of alcohol group in all tissues, except for erythrocytes and heart, and in brain, kidney, and spleen of LF group significantly increased compared to control group, whereas LF beverage extract supplementation did not restore the increased MDA towards close the control level. In addition, while ethanol caused fluctuation in antioxidant defense system constituents level as a result of oxidative stress condition in the rats, it could have not been determined the healing effects of the LF against these fluctuations. The results indicated that LF beverage extract could not be as important as diet-derived antioxidants in preventing oxidative damage in the tissues by reducing the lipid oxidation or inhibiting the production of ethanol-induced free radicals in rats. PMID:24337514

Yayalac?, Yakup; Celik, Ismail; Bat?, Bedia

2014-02-01

60

Ethanol-induced hypothermia and hyperglycemia in genetically obese mice  

SciTech Connect

Blood glucose and rectal temperatures were monitored in two strains of genetically obese mice (C57 BL/6J ob/ob) prior to and following intragastric ethanol administration in an attempt to relate the hypothermic response to ethanol to extracellular glucose concentration. In contrast to expectation, ethanol administration was typically associated with a hyperglycemia and a hypothermic response. In the ob/ob genotype, the hypothermic response was associated with pronounced hyperglycemia which was more emphatic in older animals. The data support the conclusion that ethanol-induced hypothermia is independent of blood glucose levels. In light of the known sensitivity of ob/ob mice to insulin, it is suggested further that the observed hypothermic response was not a function of the animals' ability to transport glucose into peripheral cells. The observed hyperglycemia of the obese animals was most likely stress-related

Haller, E.W.; Wittmers, L.E. Jr.

1989-01-01

61

Spontaneous rupture of a hepatic epithelioid angiomyolipoma: damage control surgery. A case report  

PubMed Central

SUMMARY Background Angiomyolipoma (AML) is a rare mesenchymal tumor composed by blood vessels, adipose tissue and smooth muscle cells in variable proportions. Although it is most often diagnosed in the kidney, this tumor may originate from any part of the liver. It is often misdiagnosed as hepatocellular carcinoma (HCC) or other benign liver tumor. We describe a case of spontaneous rupture of hepatic angiomyolipoma in a young woman, with evidence of internal hemorrhage and hemoperitoneum. Case report Liver tumor rupture is a rare but real surgical emergency. In our case it has been managed according to the trauma principles of the damage control surgery. At the time of the observation, the patient presented an instable condition, so the decision-making was oriented toward a less invasive first step of liver packing instead of a more aggressive intervention such as one shot hepatic resection. Conclusion Damage control surgery with deep parenchymal sutures of the liver and pro-coagulant tissue adhesives packing abbreviates surgical time before the development of critical and irreversible physiological endpoints and permits a more confident second time surgery. This surgical management concept helps to reduce the mortality rate and the incidence of complications not only in traumatic liver damages, it works very well in spontaneous liver ruptures as well.

OCCHIONORELLI, S.; DELLACHIESA, L.; STANO, R.; CAPPELLARI, L.; TARTARINI, D.; SEVERI, S.; PALINI, G.M.; PANSINI, G.C.; VASQUEZ, G.

2013-01-01

62

ETHANOL-INDUCED CONDITIONED PARTNER PREFERENCE IN FEMALE MICE  

PubMed Central

Drinking behavior and social context are intimately intertwined. Peer relations can promote drinking. Conversely, alcohol promotes social interaction. The present study tested female mice for ethanol-induced conditioned partner preference. Ovariectomized (OVX) C57Bl/6 females with chronic estradiol replacement (OVX+E) received saline or ethanol (1, 2 or 4 g/kg) ip and were paired 4x for 30 min each with 1 of 2 stimulus females. The test female was paired with the CS? stimulus female following saline, and was paired with the CS+ female following ethanol. After pairing, we measured proximity of the test female to the CS+ and CS? females in a 10? test. In a second study, OVX and OVX+E females were tested for conditioned partner preference (CS+ vs CS?) in response to 2.5 g/kg ethanol. In separate groups of mice, both test and stimulus females (IS+) received ethanol during pairing to determine if test mice develop conditioned partner preference for another intoxicated mouse. OVX+E test females showed conditioned partner preference for the CS+ female in response to ethanol at 2 g/kg (change in preference score for CS+: +86.6±30.0 sec/10 min), but not at 0, 1 or 4 g/kg. At 2.5 g/kg ethanol, OVX+E females developed conditioned partner preference for either IS+ (+63.6±24.0 sec) or CS+ females (+93.8±27.1 sec). OVX test females demonstrated ethanol-induced conditioned partner preference only for the IS+ female (+153.8±32.0 sec). These data demonstrate that ethanol promotes social preference in female mice, and that estradiol enhances this effect.

Wood, Ruth I.; Rice, Rachel

2013-01-01

63

Protective effects of protein hydrolysate from marine microalgae Navicula incerta on ethanol-induced toxicity in HepG2\\/CYP2E1 cells  

Microsoft Academic Search

Ethanol is independently known to cause tissue damage through various mechanisms. This study was designed to evaluate the protective effect of marine microalgae, Navicula incerta protein enzymatic hydrolysates (NEHs) against ethanol-induced hepatotoxicity in HepG2 cells transfected with human CYP2E1. Induction of CYP2E1 by ethanol is one of the central pathways by which ethanol generates a state of oxidative stress in

Kyong-Hwa Kang; Zhong-Ji Qian; BoMi Ryu; Daekyung Kim; Se-Kwon Kim

64

Hepatitis  

MedlinePLUS

... if they've been vaccinated against it. Continue Hepatitis B Hepatitis B is a more serious infection. It may lead ... of which cause severe illness and even death. Hepatitis B virus (HBV) is transmitted from person to person ...

65

Hepatitis  

MedlinePLUS

... into the food and water supply. Back Continue Hepatitis B and Hepatitis C Although hep A is a ... does — through direct contact with infected body fluids. Hepatitis B and C are even more easily passed in ...

66

A study of the effect of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C virus infection by non-invasive serum markers. A prospective study  

Microsoft Academic Search

Several beneficial effects of splenectomy on the liver integrity have been recently reported by both experimental and clinical studies. However, the effects of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C (CHC) were not studied by objective evidence. The aim of this study was to assess the effect of splenectomy on hepatic functional reserve

Magdy M. A. Elsebae; Nadia B. Abu-Zekri

2008-01-01

67

Hepatoprotective activity of Symplocos racemosa bark on carbon tetrachloride-induced hepatic damage in rats.  

PubMed

The present study aims to evaluate the hepatoprotective activity of ethanol extract of Symplocos racemosa (EESR) bark on carbon tetrachloride (CCl4)-induced hepatic damage in rats. CCl4 with olive oil (1 : 1) (0.2 ml/kg, i.p.) was administered for ten days to induce hepatotoxicity. EESR (200 and 400 mg/kg, p.o.) and silymarin (100 mg/kg p.o.) were administered concomitantly for fourteen days. The degree of hepatoprotection was measured using serum transaminases (AST and ALT), alkaline phosphatase, bilirubin, albumin, and total protein levels. Metabolic function of the liver was evaluated by thiopentone-induced sleeping time. Antioxidant activity was assessed by measuring liver malondialdehyde, glutathione, catalase, and superoxide dismutase levels. Histopathological changes of liver sample were also observed. Significant hepatotoxicity was induced by CCl4 in experimental animals. EESR treatment showed significant dose-dependent restoration of serum enzymes, bilirubin, albumin, total proteins, and antioxidant levels. Improvements in hepatoprotection and morphological and histopathological changes were also observed in the EESR treated rats. It was therefore concluded that EESR bark is an effective hepatoprotective agent in CCl4-induced hepatic damage, and has potential clinical applications for treatment of liver diseases. PMID:22022156

Wakchaure, Dhananjay; Jain, Dilpesh; Singhai, Abhay Kumar; Somani, Rahul

2011-07-01

68

Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats.  

PubMed

Amalkadi Ghrita (AG), a polyherbal formulation, was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl4)-induced hepatic damage in rats. The hepatoprotective activity of AG was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and acid phosphatase (ACP). The serum levels of total proteins and bilirubin were also estimated. The histological studies were also carried out to support the above parameters. Silymarin was used as standard drug. Administration of AG (100 and 300 mg/kg, p.o.) markedly prevented CCl4-induced elevation of levels of serum GPT, GOT, ACP, ALP, and bilirubin. The decreased level of total proteins due to hepatic damage induced by CCl4 was found to be increased in AG-treated group. The results are comparable to that of silymarin. A comparative histopathological study of liver exhibited almost normal architecture, as compared to CCl4-treated group. Hepatoprotective effect of AG is probably due to combined action of all ingredients. PMID:15013185

Achliya, Girish S; Wadodkar, Sudhir G; Dorle, Avinash K

2004-02-01

69

14-Deoxyandrographolide targets adenylate cyclase and prevents ethanol-induced liver injury through constitutive NOS dependent reduced redox signaling in rats.  

PubMed

Chronic alcoholism is one of the most common causes of liver diseases worldwide. Nitric oxide (NO) has been proposed to have potential for clinical application against chronic hepatocellular injuries. However, mechanisms underlying hepatoprotective functions of NO in ethanol-induced apoptosis are largely unknown. Sprauge-Dawley rats were exposed to ethanol for 8 weeks. Half of the ethanol-fed animals received 14-deoxyandrographolide (14-DAG) treatment for the last 4 weeks of study. Preventive effect of 14-DAG against ethanol-induced hepatotoxicity involved constitutive nitric oxide synthase (cNOS) activation followed by up-regulation of ?-glutamylcysteine synthetase activity and reduced oxidative stress. Enhanced interaction of cNOS with caveolin-1 caused down-regulation of enzyme activity and led to depletion of NO in the hepatocytes of ethanol-fed animals. 14-DAG acted as activator of adenylate cyclase and modulated cyclic AMP (cAMP) mediated expression of caveolin-1 and calmodulin. This eventually favored activation of cNOS through inhibition of cNOS-caveolin-1 interaction. Our results suggest that, protective effect of 14-DAG against ethanol-induced hepatic injury is based on its ability to reduce oxidative stress through cNOS dependent improvement of redox status. 14-DAG mediated activation of adenylate cyclase-cAMP signaling leading to up-regulation of cNOS may provide a promising approach in the prevention of liver diseases during chronic alcoholism. PMID:23764359

Mandal, Samir; Nelson, Vinod K; Mukhopadhyay, Sibabrata; Bandhopadhyay, Sukdeb; Maganti, Lakshmi; Ghoshal, Nanda; Sen, Gargi; Biswas, Tuli

2013-09-01

70

Salvianolic acid B protects against acute ethanol-induced liver injury through SIRT1-mediated deacetylation of p53 in rats.  

PubMed

Salvianolic acid B (SalB) is isolated from the traditional Chinese medical herb salvia miltiorrhiza. It has many biological and pharmaceutical activities. This study aimed to investigate the effect of SalB on acute ethanol-induced hepatic injury in rats and to explore the role of SIRT1 in this process. The results showed that pretreatment with SalB significantly reduced ethanol-induced elevation in aminotransferase activities, decreased hepatotoxic cytokine levels such as Interleukin-6 (IL-6), and increased the antioxidant enzyme activity. Moreover, SalB pretreatment reversed the increase in NF-?B, cleaved caspase-3 and decrease in B-cell lymphoma-extra large (Bcl-xL) caused by ethanol exposure. Importantly, SalB pretreatment significantly increased the expression of SIRT1, a NAD(+)-dependent deacetylase, whereas the increase in SIRT1 was accompanied by decreased acetyl-p53 expression. In HepG2 cells, SalB pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly increased the acetylation of p53, and blocked SalB-induced acetylation of p53 down-regulation. Collectively, this study indicated that SalB can alleviate acute ethanol-induced hepatocyte apoptosis through SIRT1-mediated deacetylation of p53 pathway. PMID:24769256

Li, Mingzhu; Lu, Yang; Hu, Yan; Zhai, Xiaohan; Xu, Wei; Jing, Huirong; Tian, Xiaofeng; Lin, Yuan; Gao, Dongyan; Yao, Jihong

2014-07-15

71

A Novel Murine Model to Deplete Hepatic Stellate Cells Uncovers Their Role In Amplifying Liver Damage  

PubMed Central

We have developed a novel model for depleting mouse HSCs that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic mice (TG) expressing the herpes simplex virus-Thymidine kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV). Effects of GCV were explored in primary HSCs and in vivo. Panlobular damage was provoked to maximize HSC depletion by combining carbon tetrachloride (CCl4) (centrilobular injury) with allyl alcohol (AA) (periportal injury), as well as in a bile duct ligation (BDL) model. Cell depletion in situ was quantified using dual-immunofluorescence (IF) for desmin and GFAP. In primary HSCs isolated from both untreated wild type (WT) and TG mice, GCV induced cell death in ~50% of HSCs from TG but not WT mice. In TG mice treated with CCl4+AA+GCV, there was a significant decrease in GFAP & desmin positive cells compared to WT mice (~65% reduction, p<0.01), which was accompanied by a decrease in the expression of HSC activation markers (?-SMA, ?-PDGFR and collagen I). Similar results were seen following BDL. Associated with HSC depletion in both fibrosis models, there was marked attenuation of fibrosis and liver injury, as indicated by Sirius Red/Fast Green, H&E quantification and serum ALT/AST. Hepatic expression of IL-10 and IFN-? was increased following HSC depletion. No toxicity of GCV in either WT or TG mice accounted for the differences in injury. Conclusion Activated HSCs significantly amplify the hepatic response to liver injury, further expanding this cell type's repertoire in orchestrating hepatic injury and repair.

Puche, Juan E.; Lee, Youngmin A.; Jiao, Jingjing; Aloman, Costica; Fiel, Maria I.; Munoz, Ursula; Kraus, Thomas; Lee, Tingfang; Yee, Hal F.; Friedman, Scott L.

2012-01-01

72

Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase  

PubMed Central

Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species.

Alvarez-Suarez, Jose M.; Dekanski, Dragana; Ristic, Slavica; Radonjic, Nevena V.; Petronijevic, Natasa D.; Giampieri, Francesca; Astolfi, Paola; Gonzalez-Paramas, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, Jose L.; Mezzetti, Bruno; Battino, Maurizio

2011-01-01

73

Histomorphometric Study of Fructus Psoralea on Ethanol Induced Neurodegeneration of Hippocampus in Rat  

PubMed Central

Aim: The histomophometric study of Fructus Psoralea (FP) on ethanol induced neurodegeneration of hippocampus was investigated in a rat by using micrometry. Material and Methods: The study was conducted on thirty healthy female adult wistar albino rats with regular 4-day estrus cycles. The experiment was carried out for a period of 2–4 months. The rats were divided into- SHAM operated control group (Group I) and experimental groups - overiectomised vehicle control rat ((Group II), OVX and orally treated with FP(Group III) OVX and induced with ethanol (Group IV), OVX rats induced with ethnaol and orally treated with FP (Group V). ANOVA tool was used to test the mean positive behavioural activity of all the groups. The diameter, packing density and the total number of neurons were calculated from toluidine blue stained histological section by using micrometry. The statistical package SPSS (17.0 VERSION) was used. Statistical significance was defined as p < 0.05. Data was expressed as mean ± SEM. Discussion: In animal studies, ethanol was found to significantly inhibit neuronal activity in the CA1 and CA3 pyramidal cell layers of the hippocampus. FP increase the number of cholinergic neurons in the basal forebrain which in turn leads to increased function of hippocampus, a structure heavily implicated in behavioural activity and memory consolidation. Conclusion: People with extensive hippocampal damage may experience amnesia, learning and memory disabilities. Hence the herb FP may be used as an adjuvant to treat the above neurological disorders.

Ramar, Sivanandan; P., Saraswathi

2013-01-01

74

Histomorphometric study of fructus psoralea on ethanol induced neurodegeneration of hippocampus in rat.  

PubMed

Aim: The histomophometric study of Fructus Psoralea (FP) on ethanol induced neurodegeneration of hippocampus was investigated in a rat by using micrometry. Material and Methods: The study was conducted on thirty healthy female adult wistar albino rats with regular 4-day estrus cycles. The experiment was carried out for a period of 2-4 months. The rats were divided into- SHAM operated control group (Group I) and experimental groups - overiectomised vehicle control rat ((Group II), OVX and orally treated with FP(Group III) OVX and induced with ethanol (Group IV), OVX rats induced with ethnaol and orally treated with FP (Group V). ANOVA tool was used to test the mean positive behavioural activity of all the groups. The diameter, packing density and the total number of neurons were calculated from toluidine blue stained histological section by using micrometry. The statistical package SPSS (17.0 VERSION) was used. Statistical significance was defined as p < 0.05. Data was expressed as mean ± SEM. Discussion: In animal studies, ethanol was found to significantly inhibit neuronal activity in the CA1 and CA3 pyramidal cell layers of the hippocampus. FP increase the number of cholinergic neurons in the basal forebrain which in turn leads to increased function of hippocampus, a structure heavily implicated in behavioural activity and memory consolidation. Conclusion: People with extensive hippocampal damage may experience amnesia, learning and memory disabilities. Hence the herb FP may be used as an adjuvant to treat the above neurological disorders. PMID:24086839

Ramar, Sivanandan; P, Saraswathi

2013-08-01

75

ACTIVATION OF NEUTRAL SPHINGOMYELINASE PARTICIPATES IN ETHANOL-INDUCED APOPTOSIS IN HEP G2 CELLS  

Microsoft Academic Search

The mechanism underlying ethanol-induced apoptosis in liver cells is not clear. Sphingomyelin (SM) metabolism is a novel signal transduction pathway that has an impact on apoptosis in many cell types. We investigated whether the SM pathway is invol ved in ethanol-induced apoptosis in the liver. Hep G2 cells were treated with ethanol followed by assaying apoptosis, sphingomyelin ase (SMase) activity,

JIAN-JUN LIU; JI-YAO WANG; ERIK HERTERVIG; YAJUN CHENG; ĹKE NILSSON; RUI-DONG DUAN

2000-01-01

76

The involvement of phospholipase A(2) in ethanol-induced gastric muscle contraction.  

PubMed

To understand the underlying mechanism of ethanol in tonic contraction, the effect of ethanol on phospholipase A(2) and phospholipase C activities and the effects of phospholipase inhibitors on ethanol-induced contraction of cat gastric smooth muscle were tested. Circular muscle strips (2.0 x 0.2 cm) obtained from the fundus of cat stomach were used to measure isometric contraction. Ethanol elicited tonic contraction and activated phospholipase A(2) activity in a dose-dependent manner. Phospholipase A(2) inhibitors, manoalide (0.1--10 microM) and oleyloxyethyl phosphorylcholine (1--10 microM), significantly inhibited ethanol-induced contraction. Furthermore, 342 mM ethanol-induced contraction was significantly inhibited by cyclooxygenase inhibitors, ibuprofen (10--100 microM) and indomethacin (10--100 microM), but not by lipoxygenase inhibitors. On the other hand, phospholipase C inhibitors had no effect on ethanol-induced contraction, indicating that phospholipase C is not involved in ethanol-induced contraction. It is suggested from the above results that ethanol-induced contraction in cat gastric smooth muscle is, in part, mediated by phospholipase A(2) and cyclooxygenase pathways. PMID:11226404

Sim, S S; Choi, J C; Min, D S; Rhie, D J; Yoon, S H; Hahn, S J; Kim, C J; Kim, M S; Jo, Y H

2001-02-16

77

Red Mold Rice against Hepatic Inflammatory Damage in Zn-deficient Rats  

PubMed Central

The protective effect of red mold rice (RMR) against liver injury in rats fed with a Zn-deficient diet for 12 weeks was investigated in this study. Rats were orally administered RMR (151 mg/kg body weight or 755 mg/kg body weight; 1 × dose or 5 × dose, respectively) with or without Zn once a day for 4 consecutive weeks. The severity of liver damage was evaluated by measuring the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in Zn-deficient rats. RMR significantly inhibited the elevation of serum ALT levels by Zn-deficient induction. Hepatic antioxidase activity was also significantly increased in the RMR + Zn group (RZ), thereby suppressing the productions of reactive oxygen species (ROS) and proinflammatory cytokines in the liver of Zn-deficient rats. These findings suggested that RMR exerted hepatoprotective effects against Zn deficiency-induced liver inflammation.

Lee, Bao-Hong; Hsu, Wei-Hsuan; Pan, Tzu-Ming

2012-01-01

78

Angiotensin Receptor Blockade Recovers Hepatic UCP2 Expression and Aconitase and SDH Activities and Ameliorates Hepatic Oxidative Damage in Insulin Resistant Rats  

PubMed Central

Metabolic syndrome (MetS) is commonly associated with elevated renin-angiotensin system, oxidative stress, and steatohepatitis with down-regulation of uncoupling proteins (UCPs). However, the mechanisms linking renin-angiotensin system, steatosis, and UCP2 to hepatic oxidative damage during insulin resistance are not described. To test the hypothesis that angiotensin receptor activation contributes to decreased hepatic UCP2 expression and aconitase activity and to increased oxidative damage after increased glucose intake in a model of MetS, lean and obese Long Evans rats (n = 10/group) were randomly assigned to the following groups: 1) untreated Long Evans Tokushima Otsuka (lean, strain control), 2) untreated Otsuka Long Evans Tokushima Fatty (OLETF) (MetS model), 3) OLETF + angiotensin receptor blocker (ARB) (10 mg olmesartan/kg·d × 6 wk), 4) OLETF + high glucose (HG) (5% in drinking water × 6 wk), and 5) OLETF + ARB + HG (ARB/HG × 6 wk). HG increased body mass (37%), plasma triglycerides (TGs) (35%), plasma glycerol (87%), plasma free fatty acids (28%), and hepatic nitrotyrosine (74%). ARB treatment in HG decreased body mass (12%), plasma TG (15%), plasma glycerol (23%), plasma free fatty acids (14%), and hepatic TG content (42%), suggesting that angiotensin receptor type 1 (AT1) activation and increased adiposity contribute to the development of obesity-related dyslipidemia. ARB in HG also decreased hepatic nitrotyrosine and increased hepatic UCP2 expression (59%) and aconitase activity (40%), as well as antioxidant enzyme activities (50-120%), suggesting that AT1 activation also contributes to protein oxidation, impaired lipid metabolism, and antioxidant metabolism in the liver. Thus, in addition to promoting obesity-related hypertension, AT1 activation may also impair lipid metabolism and antioxidant capacity, resulting in steatosis via decreased UCP2 and tricarboxylic acid cycle activity.

Montez, Priscilla; Vazquez-Medina, Jose Pablo; Rodriguez, Ruben; Thorwald, Max A.; Viscarra, Jose A.; Lam, Lisa; Peti-Peterdi, Janos; Nakano, Daisuke; Nishiyama, Akira

2012-01-01

79

GABAergic Modulation of Ethanol-Induced Motor Impairment  

PubMed Central

Direct or indirect pharmacological manipulation of ?-aminobutyric acid (GABA) receptor activity was examined in relation to the motor incoordinating actions of ethanol in the rat. Ethanol (1.13–3.0 g/kg i.p.) caused a dose-dependent increase in the height of aerial righting. This motor impairment was increased selectively by intracisternal injection of the GABA agonists muscimol (0.10 ?g), 4,5,6,7-tetrahydroisoxazole(5,4-c) pyridin(3-ol) (1.0 ?g) and GABA (1000 ?g). The GABA antagonist, bicuculline (1.0 and 5.0 ?g intracisternally), reduced impairment. Thus, direct manipulation of GABA receptor activity modulated motor incoordination caused by ethanol. In addition, indirect-acting GABA-mimetics, such as ?-acetylenic GABA (100 mg/kg i.p.), aminooxyacetic acid (50 mg/kg i.p.), ethanolamine-O-sulfate (250 mg/kg i.p.) and L-2,4-diaminobutyric acid (600 mg/kg i.p.) all potentiated the increase in the height of aerial righting caused by ethanol treatment. Failure of ethanol to modify the binding of [3H]muscimol to cerebral cortical membranes in vitro suggested there was no direct competition for GABA binding sites or facilitation of the binding of GABA to these sites by ethanol. Also, no simple relationship was observed between the degree of motor impairment caused by either ethanol or ?-acetylenic GABA and changes in GABA concentration in three brain areas. Although GABAergic neurons may be involved in the mechanism underlying ethanol-induced depression of motor coordination, the interaction does not involve a direct activation of GABA receptors by ethanol.

FRYE, GERALD D.; BREESE, GEORGE R.

2011-01-01

80

Dietary oxidized fat prevents ethanol-induced triacylglycerol accumulation and increases expression of PPARalpha target genes in rat liver.  

PubMed

Alcoholic fatty liver results from an impaired fatty acid catabolism due to blockade of PPARalpha and increased lipogenesis due to activation of sterol regulatory element-binding protein (SREBP)-1c. Because both oxidized fats (OF) and conjugated linoleic acids (CLA) have been demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that these fats are able to prevent ethanol-induced triacylglycerol accumulation in the liver by upregulation of PPARalpha-responsive genes. Forty-eight male rats were assigned to 6 groups and fed isocaloric liquid diets containing either sunflower oil (SFO) as a control fat, OF prepared by heating of SFO, or CLA, in the presence and absence of ethanol, for 4 wk. Administration of ethanol lowered mRNA concentrations of PPARalpha and the PPARalpha-responsive genes medium chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, acyl-CoA oxidase, carnitine palmitoyl-CoA transferase I, and cytochrome P450 4A1 and increased triacylglycerol concentrations in the liver (P < 0.05). OF increased hepatic mRNA concentrations of PPARalpha-responsive genes and lowered hepatic triacylglycerol concentrations compared with SFO (P < 0.05) whereas CLA did not. Rats fed OF with ethanol had similar mRNA concentrations of PPARalpha-responsive genes and similar triacylglycerol concentrations in the liver as rats fed SFO or CLA without ethanol. In contrast, hepatic mRNA concentrations of SREBP-1c and fatty acid synthase were not altered by OF or CLA compared with SFO. This study shows that OF prevents an alcohol-induced triacylglycerol accumulation in rats possibly by upregulation of hepatic PPARalpha-responsive genes involved in oxidation of fatty acids, whereas CLA does not exert such an effect. PMID:17182804

Ringseis, Robert; Muschick, Alexandra; Eder, Klaus

2007-01-01

81

Therapeutic efficacy of silymarin from milk thistle in reducing manganese-induced hepatic damage and apoptosis in rats.  

PubMed

Oxidative stress has been proposed as a possible mechanism involved in manganese (Mn) toxicity. Using natural antioxidants against metal-induced hepatotoxicity is a modern approach. The present study investigated the beneficial role of silymarin, a natural flavonoid, in Mn-induced hepatotoxicity focusing on histopathology and biochemical approaches. Male Wistar rats were exposed orally to manganese chloride (20 mg/mL) for 30 days followed by intraperitoneal cotreatment with silymarin (100 mg/kg). Exposure to Mn resulted in a significant elevation of the plasma marker enzyme activities and bilirubin level related to liver dysfunction of reactive oxygen species (ROS) production and hepatic oxidative stress indices. This metal reduced the activities of superoxide dismutase, catalase and glutathione peroxidase and nonenzymatic antioxidant levels such as reduced glutathione, total sulfhydryl groups and vitamin C. In addition, it caused hepatic hemorrhage, cellular degeneration and necrosis of hepatocytes as indicated by liver histopathology and DNA fragmentation studies. Coadministration of silymarin alleviated Mn oxidative damage effects by inhibiting ROS generation. Histological studies also supported the beneficial role of silymarin against Mn-induced hepatic damages. Combining all, results suggested that silymarin could protect hepatic tissues against Mn-induced oxidative stress probably through its antioxidant activity. Therefore, its supplementation could provide a new approach for the reduction in hepatic complication due to Mn poisoning. PMID:22899727

Chtourou, Y; Garoui, Em; Boudawara, T; Zeghal, N

2013-01-01

82

Reversibility of hepatic histological damage after surgical temporary obstruction of the common bile duct in a murine model.  

PubMed

The reversibility of hepatic histological damage after restoring bile flow in a murine model was assessed. 25 male Balb C mice (25-35 g, age 6 weeks) were divided into 5 groups and their common bile duct (CBD) fastened to obstruct the release of gall bladder and liver contents. Group I, CBD untied at day 10, group II at day 15, and groups III and IV at days 20 and 30, respectively. Hematoxilin-eosin stained liver slices were analysed 0, 5, 10 and 20 days after restoring bile flow. Group I showed slight histological lesions (second stage), as cholangiolar bile pigment concretion, pericholangiolar and portal collagen accumulation; group II, mild lesions (third stage), as cholangiolar hamartomatous proliferation and bile duct portal fibrosis; group III showed severe lesions (fourth stage), as loss of functional parenchyma, and also the second and first stage lesions. Group IV died before 30 days. First stage corresponds to absent lesions (control group). Group I recovered totally, group II recovered only from slight lesions and group III had irreversible damage. Severity of lesions increased gradually and accumulatively, irreversible hepatic damage was achieved at 20 days and is deadly at 30 days. Our model of temporary CBD obstruction was suitable to assess reversibility of hepatic histological damage. PMID:23675215

Olguín, H Juárez; Hernández, J L Figueroa; Guzman, D Calderón; Medina, R Alemón

2011-03-01

83

Reversibility of Hepatic Histological Damage after Surgical Temporary Obstruction of the Common Bile Duct in a Murine Model  

PubMed Central

The reversibility of hepatic histological damage after restoring bile flow in a murine model was assessed. 25 male Balb C mice (25-35 g, age 6 weeks) were divided into 5 groups and their common bile duct (CBD) fastened to obstruct the release of gall bladder and liver contents. Group I, CBD untied at day 10, group II at day 15, and groups III and IV at days 20 and 30, respectively. Hematoxilin-eosin stained liver slices were analysed 0, 5, 10 and 20 days after restoring bile flow. Group I showed slight histological lesions (second stage), as cholangiolar bile pigment concretion, pericholangiolar and portal collagen accumulation; group II, mild lesions (third stage), as cholangiolar hamartomatous proliferation and bile duct portal fibrosis; group III showed severe lesions (fourth stage), as loss of functional parenchyma, and also the second and first stage lesions. Group IV died before 30 days. First stage corresponds to absent lesions (control group). Group I recovered totally, group II recovered only from slight lesions and group III had irreversible damage. Severity of lesions increased gradually and accumulatively, irreversible hepatic damage was achieved at 20 days and is deadly at 30 days. Our model of temporary CBD obstruction was suitable to assess reversibility of hepatic histological damage.

Olguin, H. Juarez; Hernandez, J. L. Figueroa; Guzman, D. Calderon; Medina, R. Alemon

2011-01-01

84

Hawk tea (Litsea coreana Levl. var. lanuginose) attenuates CCl4-induced hepatic damage in Sprague-Dawley rats  

PubMed Central

Hawk tea (Litsea coreana Levl. var. lanuginose) is a traditional Chinese drink similar to green tea. In the present study, the preventive effects of Hawk tea on hepatic damage induced by carbon tetrachloride (CCl4) were studied in Sprague-Dawley rats. Silymarin was used as a positive control. Hawk tea was successfully shown to prevent hepatic damage in the rats. Serum levels of AST, ALT and LDH were significantly decreased when the rats were treated with varying concentrations of Hawk tea compared with silymarin (P<0.05). The lowest enzyme activities were exhibited in the 400 mg/kg Hawk tea group. This group showed reduced levels of the serum proinflammatory cytokines IL-6, IFN-? and TNF-?. In particular, the IFN-? level decreased markedly compared with the other concentration groups. The histopathology sections of liver tissue in the 400 mg/kg Hawk tea group recovered well from the CCl4 damage, but the sections of the other concentration groups showed necrosis to a more serious degree. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-? and IL-1? in the rat livers were tested. The 400 mg/kg Hawk tea group showed significantly decreased mRNA and protein expression levels of iNOS, COX-2, TNF-? and IL-1? compared with the control group. Accordingly, 400 mg/kg Hawk tea potentially contributes to the prevention of CCl4-induced hepatic damage in vivo. A 200 or 100 mg/kg dose of Hawk tea also demonstrated preventive effects against hepatic damage.

ZHAO, XIN

2013-01-01

85

Protective effect of Aquilegia vulgaris L. on aflatoxin B(1)-induced hepatic damage in rats.  

PubMed

The aim of the study was to investigate the effect of ethanol and ethyl acetate extract obtained from Aquilegia vulgaris L. on microsomal lipid peroxidation, reduced glutathione level and antioxidant enzymes activity in the liver of rats intoxicated with aflatoxin B(1) (AFB(1)). Animals were pretreated with 12 daily p.o. doses of the extracts tested (100mg/kg body weight). Then AFB(1) was administered intraperitoneally at a single dose of 1.5mg/kg b.w. to evoke the liver damage. ?-Tocopherol was used as a positive control. Reduced glutathione (GSH) was depleted in aflatoxin-treated rats by 80% in comparison with that in the controls. The extracts restored the GSH concentration up to the basal level. Microsomal lipid peroxidation stimulated by Fe(2+)/ascorbate (assessed by measuring TBARS) was enhanced in AFB(1)-treated rats by 28% as compared to that in the control group. The extracts caused a decrease in TBARS level by 40% and 27%. Only two antioxidant enzymes were affected by AFB(1) administration. The activity of catalase was reduced by 24% and the activity of glutathione-S-transferase (GST) was increased by 33%. The pretreatment with ethyl acetate and ethanol extract reduced the GST activity by 76% and 30%, respectively. No significant changes in the activity of other antioxidant enzymes were observed in rats treated with the extracts and AFB(1). It can be concluded that multiple pretreatment with the extracts obtained from A. vulgaris attenuated aflatoxin B(1)-induced hepatic damage as evidenced by inhibition of lipid peroxidation and preventing reduced glutathione depletion. PMID:21783687

Jodynis-Liebert, Jadwiga; Mat?awska, Irena; Bylka, Wies?awa; Murias, Marek

2006-07-01

86

Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats  

PubMed Central

BACKGROUND/OBJECTIVES This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.

Jang, Han I; Do, Gyeong-Min; Lee, Hye Min; Ok, Hyang Mok; Shin, Jae-Ho

2014-01-01

87

Protective role ofPhyllanthus niruri against nimesulide induced hepatic damage.  

PubMed

Present study aimed to evaluate the protective role of the aqueous extract of Phyllanthus niruri (P. niruri) against nimesulide-induced hepatic disoder in mice by determining levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) in serum and also by measuring the hepatic content of the antioxidant enzymes, superoxide dismitase (SOD) and catalase (CAT); the free radical scavenger, reduced glutathione (GSH) and thiobarbituric acid reacting substances (TBARS). Aqueous extract of P. niruri was administered either orally or intraperitoneally in different doses and times as needed for the experiments. Intraperitoneal of the extract (100 mg/kg body weight for seven days) reduced nimesulide (750 mg/kg body weight for 3 days) induced increased levels of GOT (37.0±1.8 units/ml in control group vs. 91.8±2.0 units/ml in nimesulide treated group vs. 35.0±1.0 units/ml in extract treated group), GPT (30.0±2.1 units/ml in control group vs. 88.4±2.9 units/ml in nimesulide treated group vs. 34.1±1.8 units/ml in extract treated group), and ALP (7.86±0.47 KA units/ml in control group vs. 23.80±0.60 KA units/ml in nimesulide treated group vs. 7.30±0.40 KA units/ml, in extract treated group) to almost nomal. In addition, P. niruri restored the nimesulide induced alterations of hepatic SOD (550±20 units/mg total protein in control group vs. 310±13 units/mg total protein in nimesulide treated group vs. 515±10 units/mg total protein in extract treated group), CAT (99.5±2 units/mg total protein in control group vs. 25.0±1.5 units/mg total protein in nimesulide treated group vs. 81.0±0.8 units/mg total protein in extract treated group), GSH (90±3 nmoles/mg total protein in control group vs. 17±4.2 nmoles/mg total protein in nimesulide treated group vs. 81±1 nmoles/mg total protein in extract treated group) and TBARS (measured as MDA, 36.6±3.0 nmoles/g liver tissue in control group vs. 96.3±5.2 nmoles/g liver tissue in nimesulide treated group vs. 41.2±1.7 nmoles/g liver tissue in extract treated group) contents. Dose-dependent studies showed that the herb could protect liver even if the nimesulide-induced injury is severe. Intraperitoneal administration of the extract showed better protective effect than oral administration. Combining all, the data suggest that P. niruri possesses hepatoprotective activity against nimesulide-induced liver toxicity and probably acts via an antioxidant defense mechanism. To the best of our knowledge, this is the first report of the hepatoprotective action of P. niruri against nimesulide induced liver damage. PMID:23105663

Chatterjee, Mary; Sil, Parames C

2007-03-01

88

Diabetes-Induced Hepatic Pathogenic Damage, Inflammation, Oxidative Stress, and Insulin Resistance Was Exacerbated in Zinc Deficient Mouse Model  

PubMed Central

Objectives Zinc (Zn) deficiency often occurs in the patients with diabetes. Effects of Zn deficiency on diabetes-induced hepatic injury were investigated. Methods Type 1 diabetes was induced in FVB mice with multiple low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with and without Zn chelator, N,N,N?,N?-tetrakis (2-pyridylemethyl) ethylenediamine (TPEN), at 5 mg/kg body-weight daily for 4 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level and liver histopathological and biochemical changes. Results Hepatic Zn deficiency (lower than control level, p<0.05) was seen in the mice with either diabetes or TPEN treatment and more evident in the mice with both diabetes and TPEN. Zn deficiency exacerbated hepatic injuries, shown by further increased serum ALT, hepatic lipid accumulation, inflammation, oxidative damage, and endoplasmic reticulum stress-related cell death in Diabetes/TPEN group compared to Diabetes alone. Diabetes/TPEN group also showed a significant decrease in nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and transcription action along with significant increases in Akt negative regulators, decrease in Akt and GSK-3? phosphorylation, and increase in nuclear accumulation of Fyn (a Nrf2 negative regulator). In vitro study with HepG2 cells showed that apoptotic effect of TPEN at 0.5–1.0 µM could be completely prevented by simultaneous Zn supplementation at the dose range of 30–50 µM. Conclusions Zn is required for maintaining Akt activation by inhibiting the expression of Akt negative regulators; Akt activation can inhibit Fyn nuclear translocation to export nuclear Nrf2 to cytoplasm for degradation. Zn deficiency significantly enhanced diabetes-induced hepatic injury likely through down-regulation of Nrf2 function.

Zhang, Chi; Lu, Xuemian; Tan, Yi; Li, Bing; Miao, Xiao; Jin, Litai; Shi, Xue; Zhang, Xiang; Miao, Lining; Li, Xiaokun; Cai, Lu

2012-01-01

89

Reduction of ethanol-induced ocular abnormalities in mice through dietary administration of N-acetylcysteine.  

PubMed

N-acetylcysteine (NAC) is a derivative of the amino acid l-cysteine, which, previously, has been shown to protect against ethanol-induced apoptosis during early development. Ongoing research demonstrates that NAC is also proving clinically beneficial in reducing oxidative stress-mediated lung, liver, and kidney damage, with protection likely resulting from a NAC-mediated increase in glutathione levels. In the present study, the hypothesis that coadministration of NAC and ethanol by means of liquid diet on days 7 and 8 of pregnancy in mice would reduce ethanol's teratogenicity was tested. For this work, adult nonpregnant female mice were acclimated to a liquid diet containing ethanol for 16 days, withdrawn from the ethanol, bred, and then returned to the liquid diet containing 4.8% ethanol and/or either 0.5 or 1-mg NAC/mL diet on their seventh and eighth days of pregnancy. At the concentrations used, the mice received NAC dosages of approximately 300 or 600 mg/kg/day and achieved peak blood ethanol concentrations (BEC) that averaged approximately 200mg/dL. There was no difference in BEC between the ethanol-alone and ethanol plus 600 mg/kg NAC group. After maternal euthanasia, gestational day (GD) 14 fetuses were removed, fixed, weighed, and examined for the presence and severity of ocular abnormalities, a readily assessed endpoint that results from GD 7 and 8 ethanol exposures. Although the lower dosage of NAC (300 mg/kg) resulted in a decrease in the incidence of ocular defects in both the left and right eyes, this reduction was not statistically significant. However, doubling the NAC concentration did yield a significant change; as compared with the group treated with ethanol alone, the incidence of ocular abnormalities was diminished by 22%. These results show the potential of an orally administered compound with proven clinical efficacy to reduce ethanol's teratogenic effects and support the premise that oxidative damage plays an important mechanistic role in fetal alcohol spectrum disorders. PMID:21112471

Parnell, Scott E; Sulik, Kathleen K; Dehart, Deborah B; Chen, Shao-yu

2010-01-01

90

Ethanol-Induced Depletion of Cerebellar Guanosine 3',5'-Cyclic Monophosphate Levels.  

National Technical Information Service (NTIS)

Single doses of ethanol induce a severe depletion (95 percent) of cerebellar guanosine 3-5-cyclic monophosphate (C-GMP) levels within 1 hour after administration. The degree of this depletion is a function of the amount of ethanol in the blood. Interactio...

J. D. Redos G. N. Catravas W. A. Hunt

1976-01-01

91

ALTERED RA SIGNALING IN THE GENESIS OF ETHANOL-INDUCED LIMB DEFECTS  

EPA Science Inventory

Altered RA Signaling in the Genesis of Ethanol-Induced Limb Defects Johnson CS(1), Sulik KK(1,2) Hunter, ES III(3) (1) Dept of Cell and Developmental Biology, UNC-Chapel Hill (2) Bowles Center for Alcohol Studies, UNC-CH (3) NHEERL, ORD, US EPA, RTP, NC Administr...

92

Nicotinamide Protects against Ethanol-Induced Apoptotic Neurodegeneration in the Developing Mouse Brain  

Microsoft Academic Search

BackgroundExposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginning of third trimester of gestation and continues for several years after birth in humans, whilst occuring in the first two postnatal weeks in mice. Administration

Alessandro Ieraci; Daniel G Herrera

2006-01-01

93

Zinc inhibits ethanol-induced HepG2 cell apoptosis  

SciTech Connect

Alcohol consumption produces a variety of metabolic alterations in liver cells, associated with ethanol oxidation and with nonoxidative metabolism of ethanol, among others apoptosis of hepatocytes. As zinc is known as a potent antioxidant and an inhibitor of cell apoptosis, the aim of this paper was to investigate whether zinc supplementation could inhibit ethanol-induced HepG2 apoptosis, and whether this inhibition was connected with attenuation of oxidative stress and modulation of FasR/FasL system expression. The results indicated that zinc supplementation significantly inhibited ethanol-induced HepG2 cell apoptosis (measured by cytochrome c release from mitochondria and caspase-3 activation) by attenuation of reactive oxygen species (ROS) production, increase in the cellular level of GSH, inhibition of ethanol-induced sFasR and FasL overexpression and caspase-8 activation. These results indicate that zinc can inhibit ethanol-induced hepatocyte apoptosis by several independent mechanisms, among others by an indirect antioxidative effect and probably by inhibition of caspase-8 and caspase-9 activation.

Szuster-Ciesielska, Agnieszka [Department of Virology and Immunology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin (Poland)], E-mail: szustera@hektor.umcs.lublin.pl; Plewka, Krzysztof [Department of Virology and Immunology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin (Poland); Daniluk, Jadwiga [Department and Clinic of Gastroenterology, University Medical School, Jaczewskiego 8, 20-950 Lublin (Poland); Kandefer-Szerszen, Martyna [Department of Virology and Immunology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin (Poland)

2008-05-15

94

Y-27632 inhibits ethanol-induced increase in intestinal epithelial barrier permeability.  

PubMed

The present study aimed to investigate the effect of Y-27632, an inhibitor of the Rho-associated protein kinase (ROCK), which belongs to a family of downstream effectors of activated RhoA, on the ethanol-induced increase in permeability of the intestinal epithelial barrier (IEB). The in vitro model of IEB was established usiung Caco-2 cells, and the cells were pretreated with Y-27632 prior to treatment with ethanol for 60 min. Transepithelial resistance (TEER) and paracellular marker Lucifer yellow flux measurements were performed to assess the IEB permeability. The localization and expression of tight junction (TJ)-associated proteins were detected by immunofluorescence and western blot analysis, respectively. Y-27632 partially inhibited epithelial leakage and restored normal TEER values in the IEB. Immunofluorescence and western blot analysis results indicated that ethanol induces a shift from the insoluble to the soluble fractions of claudin-1, and that the ethanol-induced decreased expression of the zonula occludens-1 (ZO-1) protein is restored by Y-27632. In conclusion, our results suggest that ROCK may play a key role in the ethanol-induced increase of IEB permeability. PMID:24643688

Tong, Jing; Wang, Ying; Chang, Bing; Zhang, Dai; Wang, Bingyuan

2014-06-01

95

Lithium blocks ethanol-induced modulation of protein kinases in the developing brain  

SciTech Connect

Lithium has been shown to be neuroprotective against various insults including ethanol exposure. We previously reported that ethanol-induced apoptotic neurodegeneration in the postnatal day 7 (P7) mice is associated with decreases in phosphorylation levels of Akt, glycogen synthase kinase-3{beta} (GSK-3{beta}), and AMP-activated protein kinase (AMPK), and alteration in lipid profiles in the brain. Here, P7 mice were injected with ethanol and lithium, and the effects of lithium on ethanol-induced alterations in phosphorylation levels of protein kinases and lipid profiles in the brain were examined. Immunoblot and immunohistochemical analyses showed that lithium significantly blocked ethanol-induced caspase-3 activation and reduction in phosphorylation levels of Akt, GSK-3{beta}, and AMPK. Further, lithium inhibited accumulation of cholesterol ester (ChE) and N-acylphosphatidylethanolamine (NAPE) triggered by ethanol in the brain. These results suggest that Akt, GSK-3{beta}, and AMPK are involved in ethanol-induced neurodegeneration and the neuroprotective effects of lithium by modulating both apoptotic and survival pathways.

Chakraborty, Goutam [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Chemistry and Biochemistry, Montclair State University, Upper Montclair, NJ 07043 (United States); Saito, Mitsuo [Division of Analytical Psychopharmacology, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Psychiatry, New York University Medical Center, New York, NY 10016 (United States); Mao, Rui-Fen; Wang, Ray [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Vadasz, Csaba [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Psychiatry, New York University Medical Center, New York, NY 10016 (United States); Saito, Mariko [Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962 (United States); Department of Psychiatry, New York University Medical Center, New York, NY 10016 (United States)], E-mail: marsaito@nki.rfmh.org

2008-03-14

96

Zinc inhibits ethanol-induced HepG2 cell apoptosis.  

PubMed

Alcohol consumption produces a variety of metabolic alterations in liver cells, associated with ethanol oxidation and with nonoxidative metabolism of ethanol, among others apoptosis of hepatocytes. As zinc is known as a potent antioxidant and an inhibitor of cell apoptosis, the aim of this paper was to investigate whether zinc supplementation could inhibit ethanol-induced HepG2 apoptosis, and whether this inhibition was connected with attenuation of oxidative stress and modulation of FasR/FasL system expression. The results indicated that zinc supplementation significantly inhibited ethanol-induced HepG2 cell apoptosis (measured by cytochrome c release from mitochondria and caspase-3 activation) by attenuation of reactive oxygen species (ROS) production, increase in the cellular level of GSH, inhibition of ethanol-induced sFasR and FasL overexpression and caspase-8 activation. These results indicate that zinc can inhibit ethanol-induced hepatocyte apoptosis by several independent mechanisms, among others by an indirect antioxidative effect and probably by inhibition of caspase-8 and caspase-9 activation. PMID:18396304

Szuster-Ciesielska, Agnieszka; Plewka, Krzysztof; Daniluk, Jadwiga; Kandefer-Szersze?, Martyna

2008-05-15

97

CYP2E1 and CYP3A1/2 gene expression is not associated with the ursodeoxycholate effect on ethanol-induced lipoperoxidation.  

PubMed

Ethanol is a well-known hepatotoxicant inducing steatosis and membrane lipoperoxidation. The aim of the present study was to investigate in rats, whether the protective effect of UDC on ethanol-induced lipid peroxidation may be related with CYP2E1 and CYP3A1/2 gene expression. We showed that UDC treatment in ethanol-fed rats induced a significant decrease in liver triglyceride concentration which was closely correlated with a reduction in malondialdehyde and hydroxyalkenal levels. In chronically ethanol-fed rats, CYP2E1 and CYP3A1/2 gene expressions were increased by a post-transcriptional mechanism. These inductions, mainly of CYP2E1, could take part in alcohol-induced hepatic lipoperoxidation. UDC modified neither the specific activity, nor the protein level, nor the mRNA level of CYP2E1 when compared with control. UDC supplementation to alcohol diet did not prevent the increase in CYP2E1 expression of ethanol-fed rats. Furthermore, CYP3A1/2 protein levels were similarly increased by ethanol and ethanol plus UDC treatment. Therefore, UDC protective effect against ethanol-induced lipoperoxidation was not associated with a modification of CYP2E1 and CYP3A1/2 expression. PMID:10503926

Nguyen, T D; Oliva, L; Villard, P H; Puyoou, F; Sauze, C; Montet, A M; Lacarelle, B; Durand, A; Montet, J C

1999-01-01

98

Protective Role of Ficus carica Stem Extract against Hepatic Oxidative Damage Induced by Methanol in Male Wistar Rats  

PubMed Central

The present study was aimed to investigate the antioxidant activity of Ficus carica stem extract (FE) in methanol-induced hepatotoxicity in male Wistar rats. The rats were divided into two batches: 16 control rats (C) drinking tap water and 16 treated rats drinking Ficus carica stem extract for six weeks. Then, each group was divided into two subgroups, and one of them was intraperitoneally injected (i.p.) daily methanol at a dose of 2.37?g/kg body weight i.p. for 30 days, for four weeks. The results showed that FE was found to contain large amounts of polyphenols and carotenoids. The treatment with methanol exhibited a significant increase of serum hepatic biochemical parameters (ALT, AST, ALP, and LDH) and hepatic lipid peroxidation. Hepatic antioxidant enzymes, namely, SOD, CAT, and GSH-Px, were significantly decreased in methanol-treated animals. FE treatment prior to methanol intoxication has significant role in protecting animals from methanol-induced hepatic oxidative damage.

Saoudi, Mongi; El Feki, Abdelfattah

2012-01-01

99

Study on Oxidative Damage and Genotoxicity of Butyl Benzyl Phthalate on the Hepatic Cells of Rat  

Microsoft Academic Search

In order to study the effect of butyl benzyl phthalatee (BBP) on hepatic cells of rat, hepatic cells of rat were exposed to different dose (5 ?mol \\/ L, 20 ?mol \\/ L, 80 ?mol \\/ L) of BBP in vitro for 1 hour. Thiobarbituric acid (TBA) method , KCl-SDS precipitation method and Dinitrophenylhydrazone (DNPH) colorimetric method were used to

Qin Longjuan; Cai Fengyun; Yang Xu; Luo Qin

2010-01-01

100

Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: role of nonoxidative metabolism.  

PubMed

Chronic alcohol abuse, a major health problem, causes liver and pancreatic diseases and is known to impair hepatic alcohol dehydrogenase (ADH). Hepatic ADH-catalyzed oxidation of ethanol is a major pathway for the ethanol disposition in the body. Hepatic microsomal cytochrome P450 (CYP2E1), induced in chronic alcohol abuse, is also reported to oxidize ethanol. However, impaired hepatic ADH activity in a rat model is known to facilitate a nonoxidative metabolism resulting in formation of nonoxidative metabolites of ethanol such as fatty acid ethyl esters (FAEEs) via a nonoxidative pathway catalyzed by FAEE synthase. Therefore, the metabolic basis of ethanol-induced cytotoxicity was determined in HepG2 cells and recombinant HepG2 cells transfected with ADH (VA-13), CYP2E1 (E47) or ADH + CYP2E1 (VL-17A). Western blot analysis shows ADH deficiency in HepG2 and E47 cells, compared to ADH-overexpressed VA-13 and VL-17A cells. Attached HepG2 cells and the recombinant cells were incubated with ethanol, and nonoxidative metabolism of ethanol was determined by measuring the formation of FAEEs. Significantly higher levels of FAEEs were synthesized in HepG2 and E47 cells than in VA-13 and VL-17A cells at all concentrations of ethanol (100-800 mg%) incubated for 6 h (optimal time for the synthesis of FAEEs) in cell culture. These results suggest that ADH-catalyzed oxidative metabolism of ethanol is the major mechanism of its disposition, regardless of CYP2E1 overexpression. On the other hand, diminished ADH activity facilitates nonoxidative metabolism of ethanol to FAEEs as found in E47 cells, regardless of CYP2E1 overexpression. Therefore, CYP2E1-mediated oxidation of ethanol could be a minor mechanism of ethanol disposition. Further studies conducted only in HepG2 and VA-13 cells showed lower ethanol disposition and ATP concentration and higher accumulation of neutral lipids and cytotoxicity (apoptosis) in HepG2 cells than in VA-13 cells. The apoptosis observed in HepG2 vs. VA-13 cells incubated with ethanol appears to be mediated by release of mitochondrial cytochrome c via activation of caspase-9 and caspase-3. These results strongly support our hypothesis that diminished hepatic ADH activity facilitates nonoxidative metabolism of ethanol and the products of ethanol nonoxidative metabolism cause apoptosis in HepG2 cells via intrinsic pathway. PMID:16806343

Wu, Hai; Cai, Ping; Clemens, Dahn L; Jerrells, Thomas R; Ansari, G A Shakeel; Kaphalia, Bhupendra S

2006-10-15

101

Bile composition, plasma lipids and oxidative hepatic damage induced by calcium supplementation; effects of goat or cow milk consumption.  

PubMed

Calcium-fortified foods, especially milk and dairy products are recommended to be consumed daily for groups in risk of nutritional deficiency, including children, young adults, menopausal women, pregnant women and the elderly, however Ca-supplementation promotes gallstone formation because Ca is a nucleating factor. The objective of the current study was to assess the influence of cow or goat milk-based diets, either normal or Ca-supplemented, on bile composition, biochemical parameters and hepatic antioxidant status. Weanling male rats were randomly divided into six groups, fed standard, goat or cow milk-based diets, either with normal Ca content (5.0 g/kg), or Ca-supplemented (10.0 g/kg), for 2 weeks. Bile cholesterol concentration and output was higher in rats fed goat milk in comparison with those fed with standard and cow-milk-based diet. Ca-supplementation increased lithogenic index with the standard and cow-milk based diets, this change was not observed with the goat milk diet. Activities of plasma transaminases were also lower in the animals fed Ca-supplemented goat milk, in comparison with the other diets assayed. In general, Ca-supplement in the diet led to an increase in the hepatic oxidative damage, with an increase in the activities of all the antioxidant enzymes studied in the standard and cow milk diet, but not with goat milk. The habitual consumption of goat milk has positive effects on the plasma lipid profile, biliary composition and hepatic antioxidant defence. In addition, under our experimental conditions, Ca-supplementation of this type of milk does not increase the lithogenic index, or hepatic oxidative damage. PMID:23470261

Díaz-Castro, Javier; Alférez, María J M; López-Aliaga, Inmaculada; Nestares, Teresa; Sánchez-Alcover, Ana; Campos, Margarita S

2013-05-01

102

Effect of bark extract of Bathysa cuspidata on hepatic oxidative damage and blood glucose kinetics in rats exposed to paraquat.  

PubMed

This study investigated the effect of bark extract of Bathysa cuspidata on hepatic oxidative damage and blood glucose kinetics in rats exposed to paraquat. Wistar rats were exposed to a single dose of paraquat (30 mg/kg, i.p.) and treated with an ethanolic extract of Bathysa cuspidata (200 and 400 mg/kg). Analyses were conducted of liver edema, blood glucose, serum transaminases, alkaline phosphatase, collagen, malondialdehyde, catalase, superoxide dismutase, and histomorphometry. In the animals intoxicated with paraquat and treated with 400 mg/kg of extract, edema, hypertrophy of the nucleus of hepatocytes, serum transaminases, alkaline phosphatase, and malondialdehyde levels decreased significantly (p < .05). Catalase and superoxide dismutase activity, the number of hepatocytes per unit volume, and the glycogen proportion were maintained. The increase followed by progressive reduction of blood glucose observed in paraquat-exposed groups was significantly attenuated in the group treated with 400 mg/kg of extract (p < .05). Phytochemical analysis of the extract revealed the presence of flavonoids, proanthocyanidins, and phenolic compounds. The bark extract of Bathysa cuspidata was able to inhibit large variations in blood glucose and reduce hepatic damage in rats exposed to paraquat. This finding suggests a contribution of the extract in reducing lipid peroxidation and the morphofunctional damage to the liver parenchyma. PMID:22021167

Novaes, Rômulo Dias; Gonçalves, Reggiani Vilela; Marques, Daiane Cristina Santos; Cupertino, Marli do Carmo; Peluzio, Maria do Carmo Gouveia; Leite, Joăo Paulo Viana; Maldonado, Izabel Regina Dos Santos Costa

2012-01-01

103

Suppression of intralysosomal proteolysis aggravates structural damage and functional impairment of liver lysosomes in rats with toxic hepatitis  

SciTech Connect

This paper estimates the effect of lowering protein catabolism in the lysosomes on structural and functional properties of the latter during liver damage. For comparison, polyvinylpyrrolidone (PVP), which is inert relative to intralysosomal proteolysis, and which also accumulates largely in lysosomes of the kupffer cells of the liver, was used. The uptake of labeled bovine serum albuman (C 14-BSA) by the liver is shown and the rate of intralysosomal proteolysis is given 24 hours after administration of suramin an CCl/sub 4/ to rats. It is suggested that it is risky to use drugs which inhibit intralysosomal proteolysis in the treatment of patients with acute hepatitis.

Korolenko, T.A.; Gavrilova, N.I.; Kurysheva, N.G.; Malygin, A.E.; Pupyshev, A.B.

1986-01-01

104

Serum HCV RNA levels correlate with histological liver damage and concur with steatosis in progression of chronic hepatitis C.  

PubMed

The role of HCV RNA levels and host factors in the severity of liver injury was studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH) C patients (179 men; median age: 52 years, range 19-68; CH, 198; cirrhosis, 100) and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b, 53%; 2a/c, 28%; 3a, 7%; 4, 1.3%, and mixed 6.4%. Serum HCV RNA levels were similar for all genotypes (median: 2.8 x 10(6) eq/ml; range <0.2-69). In patients with chronic hepatitis without cirrhosis, the serum HCV RNA levels reflected the grade of liver necroinflammatory activity (R = 0.45; P < 0.001) and the stage of fibrosis (R = 0.51; P < 0.001), regardless of age, gender, HCV genotype, hepatic steatosis, and hepatic iron overload. Patients with high serum HCV RNA levels (> or =3 x 10(6) eq/ml) had higher ALT values (P < 0.002) than those with lower HCV RNA levels. Patients with normal ALT showed low HCV RNA levels (median: 0.82 x 10(6) eq/ml) and histological features of minimal or mild chronic hepatitis. Cirrhotic patients showed significantly lower levels of viremia than those with chronic hepatitis with a similar HAI. The data of a subgroup of 62 patients with an established time of infection showed that for a similar duration of disease, patients with serum HCV RNA levels > or =3 x 10(6) eq/ml had a significantly higher fibrosis score than those with lower levels. HAI and fibrosis score were significantly higher in patients with HCV RNA levels > or =3 x 10(6) eq/ml and grade 3-4 steatosis than those with lower HCV RNA levels and steatosis grades. The data indicate that the liver damage is correlated with the HCV RNA levels and that a high viral load acts together with steatosis in accelerating the progression of liver injury. PMID:11508667

Adinolfi, L E; Utili, R; Andreana, A; Tripodi, M F; Marracino, M; Gambardella, M; Giordano, M; Ruggiero, G

2001-08-01

105

Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats  

NASA Astrophysics Data System (ADS)

Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery. In orthotopic transplantation, the donor liver is exposed to periods of ischemia and when oxygenated blood is reintroduced to the liver, oxidative stress may develop and lead to graft failure. The aim of this project was to investigate whether noninvasive multiphoton and fluorescence lifetime imaging microscopy, without external markers, were useful in detecting early liver damage caused by I/R injury. Localized hepatic ischemia was induced in rats for 1 h followed by 4 h reperfusion. Multiphoton and fluorescence lifetime imaging microscopy was conducted prior to ischemia and up to 4 h of reperfusion and compared to morphological and biochemical assessment of liver damage. Liver function was significantly impaired at 2 and 4 h of reperfusion. Multiphoton microscopy detected liver damage at 1 h of reperfusion, manifested by vacuolated cells and heterogeneous spread of damage over the liver. The damage was mainly localized in the midzonal region of the liver acinus. In addition, fluorescence lifetime imaging showed a decrease in cellular metabolic activity. Multiphoton and fluorescence lifetime imaging microscopy detected evidence of early I/R injury both structurally and functionally. This provides a simple noninvasive technique useful for following progressive liver injury without external markers.

Thorling, Camilla A.; Liu, Xin; Burczynski, Frank J.; Fletcher, Linda M.; Gobe, Glenda C.; Roberts, Michael S.

2011-11-01

106

Differential effects of eugenol against hepatic inflammation and overall damage induced by ischemia/re-perfusion injury.  

PubMed

Abstract Liver injuries, liver tumor resection, and liver transplantation are known to be responsible for ischemia/reperfusion (I/R) injury that, in turn, gives rise to liver damage. This study was undertaken to investigate the possible protective effect of eugenol against the damage induced by I/R in rat livers as well as to explore possible mechanisms of action. Male rats were divided into four groups: sham-operated, I/R only, and two groups that received 10 or 100?mg eugenol/kg/day (Eug10 and Eug100, respectively) for 15 days by gavage and were then subjected to I/R, i.e. an ischemia induced for 45?min followed by re-perfusion for 6?h. The rats were euthanized and liver tissues and blood collected for examination. The results showed that I/R induced massive hepatic structural and functional damage. Eug10-treated rats had improvement in both liver function and structure, and inhibition of I/R-induced increases in serum myeloperoxidase (MPO), tumor necrosis factor (TNF)-?, as well as hepatic nuclear factor-?B (NF-?B) p65 and caspase-3 expression. Eug10 treatment also inhibited the degree of loss in reduced glutathione (GSH) and of rise in malondialdehyde (MDA) levels in liver tissues induced by I/R. In contrast, augmentation of liver damage induced by I/R was noted in Eug100-treated rats, with these hosts displaying significant increases in oxidant, inflammatory, and apoptotic markers relative to levels seen in I/R-only rats. The results of the present study provide the first evidence that a low dose of eugenol may protect the liver against I/R injury in part by decreasing levels of lipid peroxidation, down-regulating inflammatory mediators, and inhibiting apoptosis, and that a larger dose amplifies the liver injury via oxidant and inflammatory effects. PMID:24099633

Abd El Motteleb, Dalia M; Selim, Sally A; Mohamed, Ahmed M

2014-07-01

107

Hepatoprotective potential of Decalepis hamiltonii (Wight and Arn) against carbon tetrachloride-induced hepatic damage in rats  

PubMed Central

Hepatoprotective activity of the roots of Decalepis hamiltonii (Wight and Arn) was studied using carbon tetrachloride (CCl4) induced liver injury model in albino rats. The hepatotoxicity produced by acute CCl4 administration was found to be inhibited by pretreating the rats with crude methanolic extract of the roots of D. hamiltonii (Dh) prior to CCl4 induction. Hepatotoxic inhibition was measured with the decreased levels of hepatic serum marker enzymes (glutamate-pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and lipid peroxide formation. Imbalance level of glutathione (GSH) and antioxidant enzymes such as catalase, glutathione peroxidase, and glutathione reductase were normalized in rats pretreated with Dh extract followed by CCl4 administration. Pathological changes of hepatic lesions caused by CCl4 were also improved by pretreatment with the Dh root extract. The results of this study indicate that roots of D. hamiltonii could afford a significant protective action in the alleviation of CCl4-induced hepatic damage in rats.

Harish, R.; Shivanandappa, T.

2010-01-01

108

Hepatoprotective potential of Decalepis hamiltonii (Wight and Arn) against carbon tetrachloride-induced hepatic damage in rats.  

PubMed

Hepatoprotective activity of the roots of Decalepis hamiltonii (Wight and Arn) was studied using carbon tetrachloride (CCl(4)) induced liver injury model in albino rats. The hepatotoxicity produced by acute CCl(4) administration was found to be inhibited by pretreating the rats with crude methanolic extract of the roots of D. hamiltonii (Dh) prior to CCl(4) induction. Hepatotoxic inhibition was measured with the decreased levels of hepatic serum marker enzymes (glutamate-pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and lipid peroxide formation. Imbalance level of glutathione (GSH) and antioxidant enzymes such as catalase, glutathione peroxidase, and glutathione reductase were normalized in rats pretreated with Dh extract followed by CCl(4) administration. Pathological changes of hepatic lesions caused by CCl(4) were also improved by pretreatment with the Dh root extract. The results of this study indicate that roots of D. hamiltonii could afford a significant protective action in the alleviation of CCl(4)-induced hepatic damage in rats. PMID:21180469

Harish, R; Shivanandappa, T

2010-10-01

109

Effect of hepatic methyl donor status on urinary excretion and DNA damage in B6C3F1 mice treated with sodium arsenite  

Microsoft Academic Search

This study evaluated the effect of hepatic methyl donor status on the ability of sodium arsenite (2.5, 5.0 and 10.0 mg\\/kg) administered by gavage once or on four consecutive days to induce DNA damage in male B6C3F1 mice. Maintenance on a choline-deficient (CD) diet prior to treatment resulted in mice with hepatic methyl donor deficiency (HMDD) and altered arsenical metabolism,

Raymond R. Tice; Janice W. Yager; Paul Andrews; Eric Crecelius

1997-01-01

110

Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.  

PubMed

The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity. PMID:20645773

Cemek, Mustafa; Yilmaz, Ezgi; Büyükokuro?lu, Mehmet Emin

2010-07-01

111

The effects of neurotensin, ? -endorphin and bombesin on ethanol-induced behaviors in mice  

Microsoft Academic Search

The effects of the three peptides neurotensin, ß-endorphin, and bombesin on ethanol-induced behaviors were studied in mice. Intracisternal administration of these peptides to mice prolonged the duration of sleep induced by ethanol (5.2 g\\/kg). Neurotensin and ß-endorphin also enhanced thanol-induced hypothermia. None of the peptides, when administered alone, produced sleep. Lowever, all three compounds impaired the aerial righting reflex and

Daniel Luttinger; Gerald D. Frye; Charles B. Nemeroff; Arthur J. Prange Jr

1983-01-01

112

Differential effects of catecholamine antagonists on ethanol-induced excitation in mice  

Microsoft Academic Search

Catecholamine antagonists were assessed for their effects on ethanol-induced motor excitation. Motor excitation was measured in male Swiss-Webster mice using an open-field apparatus. Mice were treated with several doses of ethanol and at each dose, mice were pretreated with pimozide, a dopamine D2 antagonist, Schering 23390, a dopamine D1 antagonist, phenoxybenzamine, a noradrenergic alpha-1 antagonist, or yohimbine, a noradrenergic alpha-2

Ulrike M. Koechling; Brian R. Smith; Zalman Amit

1990-01-01

113

Neuroprotection by taurine in ethanol-induced apoptosis in the developing cerebellum  

Microsoft Academic Search

BACKGROUND: Acute ethanol administration leads to massive apoptotic neurodegeneration in the developing central nervous system. We studied whether taurine is neuroprotective in ethanol-induced apoptosis in the mouse cerebellum during the postnatal period. METHODS: The mice were divided into three groups: ethanol-treated, ethanol+taurine-treated and controls. Ethanol (20% solution) was administered subcutaneously at a total dose of 5 g\\/kg (2.5 g\\/kg at

Andrey G Taranukhin; Elena Y Taranukhina; Pirjo Saransaari; Irina M Podkletnova; Markku Pelto-Huikko; Simo S Oja

2010-01-01

114

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum  

Microsoft Academic Search

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative\\u000a diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the\\u000a cerebellum of rats. Thirty-two adult male Sprague–Dawley rats were divided into four equal groups (control, ethanol, betaine,\\u000a and betaine plus ethanol) with different dietary regimens

Masoud Alirezaei; Gholamali Jelodar; Parvin Niknam; Zeynab Ghayemi; Saeed Nazifi

115

The protective effect of thymoquinone on ethanol-induced acute gastric damage in the rat  

Microsoft Academic Search

Previous studies have indicated a pivotal role of reactive oxygen species in the pathomechanism of gastric ulcer. Recent studies demonstrated that thymoquinone (TQ) had an antioxidant effect on injuries caused by various toxic agents in different experimental models. The present study was planned to test whether TQ, the main constituent of the volatile oil of Nigella sativa seeds, was capable

S. Oktay Arslan; Ethem Gelir; Ferah Armutcu; Omer Coskun; Ahmet Gurel; Hale Sayan; I. Levent Celik

2005-01-01

116

Central Leptin and Cholecystokinin in Gastroprotection against Ethanol-Induced Damage  

Microsoft Academic Search

Background: Leptin, a product of the ob gene controlling food intake, has recently been detected in the stomach and shown to be released by cholecystokinin (CCK) and to induce gastroprotection against various noxious agents, but it is not known whether centrally applied leptin influences gastric secretion and mucosal integrity. Aims: In this study we compared the effects of leptin and

Tomasz Brzozowski; Peter C. Konturek; Stanislaw J. Konturek; Piotr Pierzchalski; Wladyslaw Bielanski; Robert Pajdo; Danuta Drozdowicz; Eckhart G. Hahn

2000-01-01

117

Naltrexone Reverses Ethanol-Induced Rat Hippocampal and Serum Oxidative Damage  

PubMed Central

Naltrexone, an antagonist of ?-opioid receptors, is clinically used as adjuvant therapy of alcohol dishabituation. The aim of the present work was to test the effect of 1?mg/kg body weight of naltrexone to revert oxidative stress-related biochemical alterations, in the hippocampus and serum of chronic alcoholic adult rats. Malondialdehyde concentration was increased and glutathione peroxidase activity was decreased in hippocampus and serum of alcohol-treated rats. Naltrexone treatment restored these alterations. The in vitro antioxidant ability of Ntx could not justify these effects considering the doses used. Thus this apparent protective effect of Ntx can only be attributed to its pharmacological effects, as herein discussed.

Almansa, Inmaculada; Barcia, Jorge M.; Lopez-Pedrajas, Rosa; Muriach, Maria; Miranda, Maria; Romero, Francisco Javier

2013-01-01

118

Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection  

PubMed Central

Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper/T-cytotoxic type-1 cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1?; MIP-1?), CCL4 (MIP-1?), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-??inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell ? chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon ?; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.

Larrubia, Juan R; Benito-Martinez, Selma; Calvino, Miryam; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad

2008-01-01

119

Mechanisms of ethanol-induced degeneration in the developing, mature, and aging cerebellum.  

PubMed

The adverse effects of acute and chronic ethanol exposure on cerebellar functions have been acknowledged for decades, in terms of impaired control of movement and balance. In addition to the motor impairment, cerebellar degeneration has recently been shown to contribute to distinct neuropsychological deficits in chronic alcoholics, as well as in children with prenatal ethanol exposure. The basic mechanisms underlying these ethanol-induced functional alterations and the related neuropathology in the cerebellum have mostly been clarified only recently. These mechanisms include: (i) excitotoxicity; (ii) dietary factors, especially thiamine depletion; (iii) glial abnormalities; (iv) changes in growth factors; (v) apoptotic mechanisms; (vi) oxidative stress; and (vii) compromised energy production. Although these mechanisms widely apply not only to the mature cerebellum, but also to the developing and the aging cerebella, the developing and the aged cerebellum have some special characteristics, which may make them even more vulnerable to ethanol-induced degeneration. These special instances will be discussed along with the general mechanisms of ethanol-induced cerebellar degeneration. PMID:18418667

Jaatinen, Pia; Rintala, Jyrki

2008-01-01

120

Differential effects of catecholamine antagonists on ethanol-induced excitation in mice.  

PubMed

Catecholamine antagonists were assessed for their effects on ethanol-induced motor excitation. Motor excitation was measured in male Swiss-Webster mice using an open-field apparatus. Mice were treated with several doses of ethanol and at each dose, mice were pretreated with pimozide, a dopamine D2 antagonist, Schering 23390, a dopamine D1 antagonist, phenoxybenzamine, a noradrenergic alpha-1 antagonist, or yohimbine, a noradrenergic alpha-2 antagonist. Each mouse was subjected to only one dose regimen, and all injections were given IP. Ethanol produced an increase in locomotor activity. The degree to which pimozide attenuated ethanol excitation decreased with increasing ethanol dosage. At the highest dose of ethanol, pimozide increased ethanol excitation. Schering 23390 attenuated ethanol-induced excitation only at doses which affected motor activity per se. Phenoxybenzamine produced a dose-dependent reduction in ethanol excitation. Yohimbine had its greatest effects at the medium dose (4.0 mg/kg). These observations seem to indicate a role for both the dopamine D2 receptor and the noradrenergic alpha-1 receptor in ethanol-induced motor excitation. PMID:2274606

Koechling, U M; Smith, B R; Amit, Z

1990-01-01

121

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum.  

PubMed

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the cerebellum of rats. Thirty-two adult male Sprague-Dawley rats were divided into four equal groups (control, ethanol, betaine, and betaine plus ethanol) with different dietary regimens and were followed up for 1 month. Total homocysteine (tHcy) of plasma and cerebellum homogenate was determined by an Axis(®) homocysteine EIA kit, and antioxidant enzyme (glutathione peroxidase (GPx), SOD, and CAT) activities of cerebellum homogenate were measured chemically by a spectrophotometer. Lipid peroxidation of cerebellum was shown by the measurement of thiobarbituric reactive substances (TBARS) via a spectrophotometer. Ethanol-induced hyperhomocysteinemia was manifested by an increase in the concentrations of tHcy in the plasma and cerebellum homogenates of the ethanol group, while ethanol-induced oxidative stress was indicated via an increase in lipid peroxidation marker (TBARS) in cerebellum homogenates of ethanol-treated rats. In contrast, betaine prevented hyperhomocysteinemia and oxidative stress in the betaine plus ethanol group as well as the betaine group. The results of the present investigation indicated that the protective effect of betaine is probably related to its ability to strengthen the cerebellum membrane cells by enhancement of antioxidant enzyme activity principally GPx, while the methyl donor effect of betaine to reduce hyperhomocysteinemia has been explained previously and confirmed in the present study. PMID:21698419

Alirezaei, Masoud; Jelodar, Gholamali; Niknam, Parvin; Ghayemi, Zeynab; Nazifi, Saeed

2011-12-01

122

Hepatitis C virus NS2 protein inhibits DNA damage pathway by sequestering p53 to the cytoplasm.  

PubMed

Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality globally, and often leads to end-stage liver disease. The DNA damage checkpoint pathway induces cell cycle arrest for repairing DNA in response to DNA damage. HCV infection has been involved in this pathway. In this study, we assess the effects of HCV NS2 on DNA damage checkpoint pathway. We have observed that HCV NS2 induces ataxia-telangiectasia mutated checkpoint pathway by inducing Chk2, however, fails to activate the subsequent downstream pathway. Further study suggested that p53 is retained in the cytoplasm of HCV NS2 expressing cells, and p21 expression is not enhanced. We further observed that HCV NS2 expressing cells induce cyclin E expression and promote cell growth. Together these results suggested that HCV NS2 inhibits DNA damage response by altering the localization of p53, and may play a role in the pathogenesis of HCV infection. PMID:23638118

Bittar, Cintia; Shrivastava, Shubham; Bhanja Chowdhury, Joydip; Rahal, Paula; Ray, Ratna B

2013-01-01

123

Protective effects of betulin and betulinic acid against ethanol-induced cytotoxicity in HepG2 cells.  

PubMed

Plant triterpenes, such as oleanolic acid and betulin were described as hepatoprotectants active against cytotoxicity of acetaminophen or cadmium. The aim of this paper is to compare the cytoprotective activity of betulin, betulinic acid and oleanolic acid against ethanol-induced cytotoxicity in HepG2 cells. The influence of three triterpenes on ethanol-induced production of superoxide anion and hydrogen peroxide was also examined. Among the examined triterpenes, betulin was the most active protectant of HepG2 cells against ethanol-induced cytotoxicity. Betulin and betulinic acid significantly decreased ethanol-induced production of superoxide anion. Oleanolic acid inhibited only ethanol- and phorbol ester-induced production of hydrogen peroxide. The results indicate that cytoprotective or antioxidative activity of triterpenes depends on their chemical structure. PMID:16227641

Szuster-Ciesielska, Agnieszka; Kandefer-Szersze?, Martyna

2005-01-01

124

The relationship between haematological indices, serum gamma-glutamyl transferase and glutamate dehydrogenase, visual hepatic damage and worm burden in cattle infected with Fasciola gigantica.  

PubMed

The association between visual hepatic damage, burden of Fasciola gigantica, serum levels of gamma glutamyl transferase (GGT) and glutamate dehydrogenase (GLDH) is described from an abattoir study of 70 cattle in the Philippines. In another abattoir study of 60 cattle, the relationship between burden of F. gigantica and haematological indices was investigated. The degree of visual hepatic damage and burden of F. gigantica were significantly positively related to levels of GGT and GLDH. Red blood cell counts and packed cell volume were significantly inversely related to worm burden, but animals compensated for reduced numbers of red blood cells by increasing red cell haemoglobin content. PMID:16923272

Molina, E C; Lozano, S P; Barraca, A P

2006-09-01

125

Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats  

PubMed Central

Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20?mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500?mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5?mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer.

Ismail, Iza Farhana; Abdul Majid, Nazia; Kadir, Farkaad A.; Al-Bayaty, Fouad; Awang, Khalijah

2012-01-01

126

Efficacy of sardinelle protein hydrolysate to alleviate ethanol-induced oxidative stress in the heart of adult rats.  

PubMed

The present study was undertaken to examine the protective effects of sardinelle proteins hydrolysate (SPH) obtained from heads and viscera against ethanol toxicity in the heart of adult rats. Twenty-four male rats of Wistar strain, weighing at the beginning of the experiment 250 to 300 g, were used in this study. They were divided into 4 groups: group (C) served as controls, group (Eth) received 30% ethanol solution at 3 g/kg body weight, group (SPH) received only 7.27 mg of SPH/kg body weight, and group (Eth-SPH) received ethanol and sardinelle proteins hydrolysate simultaneously. All treatments were made by gavage during 15 d. Treatment with ethanol revealed a significant elevation of malondialdehyde and protein carbonyl levels in the heart and of aspartate transaminase and alanine transaminase activities in plasma. Nitric oxide levels and the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase decreased. Nonenzymatic antioxidant such as reduced glutathione did not significantly change and ascorbic acid was decreased. SPH intake concomitantly with ethanol restored these parameters to near control values. These modifications confirmed histopathological aspects of the heart. The results revealed that SPH could provide protection of the myocardium against ethanol-induced oxidative damages in rats. This may be due to the high antioxidant potential of SPH. PMID:22780570

Kamoun, Zeineb; Kamoun, Alya Sellami; Bougatef, Ali; Chtourou, Yassine; Boudawara, Tahia; Nasri, Moncef; Zeghal, Najiba

2012-08-01

127

ETHANOL-INDUCED CYTOTOXICITY IN RAT PANCREATIC ACINAR AR42J CELLS: ROLE OF FATTY ACID ETHYL ESTERS  

Microsoft Academic Search

Aims: To understand the mechanism(s) of alcoholic pancreatitis and role of fatty acid ethyl esters (FAEEs, non- oxidative metabolites of ethanol) in ethanol-induced pancreatic injury. Methods: A time- and concentration-dependent synthesis of FAEEs and the cytotoxicity of ethanol and its predominant fatty acid esters were studied in rat pancreatic tumour (AR42J) cells in cultures. Role of FAEEs in ethanol-induced cytotoxicity

HAI WU; KAMLESH K. BHOPALE; G. A. S. ANSARI; BHUPENDRA S. KAPHALIA

128

Occult hepatitis B virus infection with low viremia induces DNA damage, apoptosis and oxidative stress in peripheral blood lymphocytes.  

PubMed

Occult HBV infections (OHBI) are often associated with poor therapeutic response and increased risk of developing hepatocellular carcinoma. Despite a decade of research, OHBI still remains an intricate issue and much is yet to be defined about their possible immune implications. As HBV is known to infect peripheral blood lymphocytes, the present study aimed to explore the molecular mechanisms underlying DNA damage response triggered due to OHBI in host cells. The study was divided into three groups i.e. group A (OHBI patients n=30, viral load damage response, apoptosis and oxidative stress were the studied parameters. A significant increase in the phosphorylation of DNA damage response proteins (ATM, ATR, H2AX and p53) in OHBI in comparison to controls suggested that OHBI induces DNA damage in peripheral blood lymphocytes and elicit a PI3 kinase mediated cellular response. In addition, increased DNA fragmentation, circulating nucleosome levels and mitochondrial membrane depolarization observed in OHBI group indicated that this damage might lead to cellular demise and immune hypo-responsiveness. Moreover, OHBI was also observed to be strongly associated with oxidative stress as suggested by the augmented levels of DCF fluorescence and depleted GR activity. Collectively, these results provide the basic knowledge about the genotoxic effects of OHBI in peripheral blood lymphocytes. Such studies may possibly open up new avenues for identifying novel therapeutic targets for viral hepatitis. PMID:20667493

Bhargava, Arpit; Khan, Saba; Panwar, Hariom; Pathak, Neelam; Punde, Ram P; Varshney, Subodh; Mishra, Pradyumna K

2010-10-01

129

CMZ Reversed Chronic Ethanol-Induced Disturbance of PPAR-? Possibly by Suppressing Oxidative Stress and PGC-1? Acetylation, and Activating the MAPK and GSK3? Pathway  

PubMed Central

Background Cytochrome P4502E1 (CYP2E1) has been suggested to play critical roles in the pathogenesis of alcoholic fatty liver (AFL), but the underlying mechanisms remains unclear. The current study was designed to evaluate whether CYP2E1 suppression by chlormethiazole (CMZ) could suppress AFL in mice, and to explore the underlying mechanisms. Methods Mice were treated with or without CMZ (50 mg/kg bw, i.p.) and subjected to liquid diet with or without ethanol (5%, w/v) for 4 weeks. Biochemical parameters were measured using commercial kits. The protein and mRNA levels were detected by western blot and qPCR, respectively. Histopathology and immunohistochemical assay were performed with routine methods. Results CYP2E1 inhibition by CMZ completely blocked AFL in mice, shown as the decline of the hepatic and serum triglyceride levels, and the fewer fat droplets in the liver sections. Chronic ethanol exposure led to significant decrease of the mRNA and protein levels of peroxisome proliferator-activated receptor ? (PPAR-?), which was blocked by CMZ co-treatment. CMZ co-treatment suppressed ethanol-induced oxidative stress, overproduction of tumor necrosis ? (TNF-?), and decrease of protein levels of the PPAR-? co-activators including p300 and deacetylated PGC1-?. Furthermore, CMZ co-treatment led to the activation of AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), and PI3K/Akt/GSK3? pathway. However, chronic ethanol-induced decline of acyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) protein levels was partially restored by CMZ, while the activation of autophagy appeared to be suppressed by CMZ. Conclusion These results suggested that CMZ suppressed chronic ethanol-induced oxidative stress, TNF-? overproduction, decline of p300 protein level and deacetylation of PGC1-?, and activated AMPK, MAPK, and PI3K/Akt/GSK3? pathway, which might contribute to the activation of PPAR-? and account for the protection of CMZ against AFL.

Zeng, Tao; Zhang, Cui-Li; Song, Fu-Yong; Zhao, Xiu-Lan; Xie, Ke-Qin

2014-01-01

130

Zinc pretreatment prevents hepatic stellate cells from cadmium-produced oxidative damage  

Microsoft Academic Search

Pretreatment with zinc produces tolerance to several cadmium toxic effects. This study was performed to further elucidate\\u000a the mechanism of zinc-induced tolerance to cadmium cytotoxicity in a rat hepatic stellate cell line (CFSC-2G). Twenty four\\u000a hours after seeding, cells were treated with 60 ?mol\\/L ZnCl2 for 24 h. Following zinc pretreatment, cells were exposed to 3 ?mol\\/L and 5 ?mol\\/L

V. Souza; M. del C. Escobar; L. Bucio; E. Hernfindez; M. C. Gutiérrez-Ruiz

2004-01-01

131

Hepatoprotective Activity of Cucumis trigonus Roxb. Fruitagainst CCl4 Inducesd Hepatic Damage in Rats  

PubMed Central

In India, a number of medicinal plants and their formulations are used to cure hepatic disorders in traditional systems of medicine. No systemic study has been done on protective effect of Cucumis trigonus Roxb. (Cucurbitaceae) to treat hepatic diseases. Protective action of C. trigonus fruit extracts was evaluated in this study in animal model of hepatotoxicity, which was induced by carbon tetrachloride. Forty two healthy female albino Wistar rats weighing between 180 and 200 g were divided in to seven groups of 6. Group 1 was normal control group; Group 2, the hepatotoxic group was given CCl4; Group 3 was administered standard drug (Liv-52); Groups 4-7 received pet. ether, chloroform, alcohol and aqueous fruit extract (300 mg/kg) with CCl4. The parameters studied were alanine transaminase, aspartate transaminase, alkaline phosphatase and serum bilirubin activities. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum enzyme activities, reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with chloroform and aqueous fruit extracts showed significant and alcohol extract showed highly significant decrease in the levels of serum markers, indicating the protection of hepatic cells. The results revealed that alcoholic fruit extract of Cucumis trigonus could afford highly significant protection against CCl4 induced hepatocellular injury.

Patil, Kalpana; MohammedImtiaz, Shaikh; Singh, Anoop; Bagewadi, Varsha; Gazi, Shaikh

2011-01-01

132

The DNA Damage Sensors Ataxia-Telangiectasia Mutated Kinase and Checkpoint Kinase 2 Are Required for Hepatitis C Virus RNA Replication  

Microsoft Academic Search

Cellular responses to DNA damage are crucial for maintaining genome integrity, virus infection, and preventing the development of cancer. Hepatitis C virus (HCV) infection and the expression of the HCV nonstructural protein NS3 and core protein have been proposed as factors involved in the induction of double-stranded DNA breaks and enhancement of the mutation frequency of cellular genes. Since DNA

Yasuo Ariumi; Misao Kuroki; Hiromichi Dansako; Ken-Ichi Abe; Masanori Ikeda; Takaji Wakita; Nobuyuki Kato

2008-01-01

133

Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl 4-induced hepatic damage of HEAI extract  

Microsoft Academic Search

The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl4-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs,

Won-Sik Choi; Chang-Jin Kim; Byeoung-Soo Park; Sung-Eun Lee; Gary R. Takeoka; Dong-Goo Kim; Xiang LanPiao; Jeong-Han Kim

2005-01-01

134

[Hepatoprotective properties of isoflavonoids from roots of Maackia amurensis on experimental carbon tetrachloride-induced hepatic damage].  

PubMed

Hepatoprotective properties of ethanol extract from the roots of Maackia amurensis Ruper et Maxim have been studied on the model of toxic hepatitis induced by carbon tetrachloride damage. It is established that the extract contains daidzein, 7-O-gentobiosides of isoflavonoids genistein, formononetin, pseudobabtige-nin, and 5-O-methylgenistein, and 3-O-gentobiosides of pterocarpans (6aR, 11aR)-maakiain and (6aR, 11aR)-medicarpin. The administration of extract facilitates the restoration of antioxidant protection enzymes activity and reduced glutathione level, decreases the formation of toxic peroxidation products, produces normalizing impact on liver phospholipid pattern, and improves the erythrocyte tolerance to hemolytic agents. The action of isoflavonoids from Maackia amurensis in restoration of metabolic pathways of the liver and removal of toxic stress was more effective as compared to that of the reference hepatoprotector legalon. PMID:24791337

Kushnerova, N F; Fedoreev, S A; Fomenko, S E; Sprygin, V G; Kulesh, N I; Mishchenko, N P; Veselova, M V; Momot, T V

2014-01-01

135

Hepatoprotective and antioxidant activities of flowers of Calotropis procera (Ait) R. Br. in CCl4 induced hepatic damage.  

PubMed

Hepatoprotective activity of 70% ethanolic extract of flowers of C. procera was studied against CCl4 induced hepatic injury in albino rats and mice. In addition, antioxidant activity was studied by in vitro models. Pre-treatment with 70% ethanolic extract (CPA) reduced the biochemical markers of hepatic injury like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, bilirubin, cholesterol, HDL and tissue glutathione (GSH) levels. Similarly pretreatment with CPA reduced the CCl4 induced elevation in the pentobarbitone sleeping time. Histopathological observations also revealed that pretreatment with CPA protected the animals from CCl4 induced liver damage. CPA demonstrated dose dependant reduction in the in vitro and in vivo lipid peroxidation induced by CCl4. In addition it showed dose dependant free radical scavenging activity. The results indicate that flowers of C. procera possess hepatoprotective property possibly because of its anti-oxidant activity. This property may be attributed to the quercetin related flavonoids present in the flowers of Calotropis procera. PMID:17373378

Qureshi, Absar Ahmed; Prakash, T; Patil, Tushar; Viswanath Swamy, A H M; Gouda, A Veeran; Prabhu, K; Setty, S Ramachandra

2007-03-01

136

Menhaden Oil Decreases High-Fat Diet-Induced Markers of Hepatic Damage, Steatosis, Inflammation, and Fibrosis in Obese Ldlr?/? Mice123  

PubMed Central

The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20–22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20–22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet–induced fatty liver disease in mice. Wild-type (WT) and Ldlr?/? C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF–high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1?1), and oxidative stress (heme oxygenase-1) (P ? 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr?/? mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr?/? mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20–22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet–induced markers of fatty liver disease in mice.

Depner, Christopher M.; Torres-Gonzalez, Moises; Tripathy, Sasmita; Milne, Ginger; Jump, Donald B.

2012-01-01

137

Menhaden oil decreases high-fat diet-induced markers of hepatic damage, steatosis, inflammation, and fibrosis in obese Ldlr-/- mice.  

PubMed

The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20-22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20-22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet-induced fatty liver disease in mice. Wild-type (WT) and Ldlr(-/-) C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF-high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1?1), and oxidative stress (heme oxygenase-1) (P ? 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr(-/-) mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr(-/-) mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20-22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet-induced markers of fatty liver disease in mice. PMID:22739374

Depner, Christopher M; Torres-Gonzalez, Moises; Tripathy, Sasmita; Milne, Ginger; Jump, Donald B

2012-08-01

138

Acetaminophen increases the risk of arsenic-mediated development of hepatic damage in rats by enhancing redox-signaling mechanism.  

PubMed

We evaluated whether the commonly used analgesic-antipyretic drug acetaminophen can modify the arsenic-induced hepatic oxidative stress and also whether withdrawal of acetaminophen administration during the course of long-term arsenic exposure can increase susceptibility of liver to arsenic toxicity. Acetaminophen was co-administered orally to rats for 3 days following 28 days of arsenic pre-exposure (Phase-I) and thereafter, acetaminophen was withdrawn, but arsenic exposure was continued for another 28 days (Phase-II). Arsenic increased lipid peroxidation and reactive oxygen species (ROS) generation, depleted glutathione (GSH), and decreased superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR) activities. Acetaminophen caused exacerbation of arsenic-mediated lipid peroxidation and ROS generation and further enhancement of serum alanine aminotransferase and aspartate aminotransferase activities. In Phase-I, acetaminophen caused further GSH depletion and reduction in SOD, catalase, GPx and GR activities, but in Phase-II, only GPx and GR activities were more affected. Arsenic did not alter basal and inducible nitric oxide synthase (iNOS)-mediated NO production, but decreased constitutive NOS (cNOS)-mediated NO release. Arsenic reduced expression of endothelial NOS (eNOS) and iNOS genes. Acetaminophen up-regulated eNOS and iNOS expression and NO production in Phase-I, but reversed these effects in Phase-II. Results reveal that acetaminophen increased the risk of arsenic-mediated hepatic oxidative damage. Withdrawal of acetaminophen administration also increased susceptibility of liver to hepatotoxicity. Both ROS and NO appeared to mediate lipid peroxidation in Phase-I, whereas only ROS appeared responsible for peroxidative damage in Phase-II. PMID:22120977

Majhi, Chhaya Rani; Khan, Saleem; Leo, Marie Dennis Marcus; Prawez, Shahid; Kumar, Amit; Sankar, Palanisamy; Telang, Avinash Gopal; Sarkar, Souvendra Nath

2014-02-01

139

Nicotinamide Protects against Ethanol-Induced Apoptotic Neurodegeneration in the Developing Mouse Brain  

PubMed Central

Background Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginning of third trimester of gestation and continues for several years after birth in humans, whilst occuring in the first two postnatal weeks in mice. Administration of a single dose of ethanol in 7-d postnatal (P7) mice triggers activation of caspase-3 and widespread apoptotic neuronal death in the forebrain, providing a possible explanation for the microencephaly observed in human FAS. The present study was aimed at determining whether nicotinamide may prevent ethanol-induced neurodegeneration. Methods and Findings P7 mice were treated with a single dose of ethanol (5g/kg), and nicotinamide was administered from 0 h to 8 h after ethanol exposure. The effects of nicotinamide on ethanol-induced activation of caspase-3 and release of cytochrome-c from the mitochondria were analyzed by Western blot ( n = 4–7/group). Density of Fluoro-Jade B–positive cells and NeuN-positive cells was determined in the cingulated cortex, CA1 region of the hippocampus, and lateral dorsal nucleus of the thalamus ( n = 5–6/group). Open field, plus maze, and fear conditioning tests were used to study the behavior in adult mice ( n = 31–34/group). Nicotinamide reduced the activation of caspase-3 (85.14 ± 4.1%) and the release of cytochrome-c (80.78 ± 4.39%) in postnatal mouse forebrain, too. Nicotinamide prevented also the ethanol-induced increase of apoptosis. We demonstrated that ethanol-exposed mice showed impaired performance in the fear conditioning test and increased activity in the open field and in the plus maze. Administration of nicotinamide prevented all these behavioral abnormalities in ethanol-exposed mice. Conclusions Our findings indicate that nicotinamide can prevent some of the deleterious effects of ethanol on the developing mouse brain when given shortly after ethanol exposure. These results suggest that nicotinamide, which has been used in humans for the treatment of diabetes and bullous pemphigoid, may hold promise as a preventive therapy of FAS.

Ieraci, Alessandro; Herrera, Daniel G

2006-01-01

140

Ameliorating effect of balloon flower saponin on the ethanol-induced memory impairment in mice.  

PubMed

The ameliorating effect of the root extract of Platycodon grandiflorum (Campanulaceae) on ethanol-induced cognitive dysfunction in mice was investigated. The mice with repeated administration of the root extract of P. grandiflorum, crude saponin fraction and platycoside E, a main ingredient of crude saponin fraction, showed a markedly prolonged step-through latency period (STL) on the passive avoidance task performed after acute ethanol intoxication, respectively. The present results suggest that the memory enhancing effect of the extract was ascribed mainly to the saponin fraction and that saponin of P. grandiflorum, particularly platycoside E could exert a beneficial effect on memory impairment in mice. PMID:18521966

Choi, Yeon Hee; Kim, Young Sup; Yeo, Su Jeong; Roh, Seong Hwan; Jeong, Young Chul; Kang, Jong Seong; Ryu, Shi Yong

2008-07-01

141

Evidence for the Involvement of RhoA Signaling in the Ethanol-Induced Increase in Intestinal Epithelial Barrier Permeability  

PubMed Central

In this work, we investigated the potential role of the small G protein RhoA in ethanol-induced tight junction (TJ) protein disassembly and increased intestinal epithelial barrier (IEB) permeability. Our study used Caco-2 cells as an in vitro IEB model and RhoA short hairpin RNA (shRNA) interference to establish whether RhoA plays a role in ethanol-induced TJ opening. RhoA shRNA interference partially inhibited epithelial leakage and restored normal transepithelial electrical resistance (TEER) values in the IEB. Moreover, RhoA shRNA interference prevented a shift in occludin distribution from insoluble to soluble fractions. Additionally, RhoA shRNA interference inhibited the ethanol-induced expression of zonula occludens-1 (ZO-1). Finally, RhoA shRNA interference inhibited an ethanol-induced increase in RhoA activity. The contributions of RhoA to an ethanol-induced increase in IEB permeability are associated with TJ disassembly.

Tong, Jing; Wang, Ying; Chang, Bing; Zhang, Dai; Wang, Bingyuan

2013-01-01

142

Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage  

PubMed Central

Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-?, and natural killer (NK) cell expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death–inducing receptor. IFN-? concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-?/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen–specific mechanism can be switched on by cytokines produced during active HBV infection.

Dunn, Claire; Brunetto, Maurizia; Reynolds, Gary; Christophides, Theodoros; Kennedy, Patrick T.; Lampertico, Pietro; Das, Abhishek; Lopes, A. Ross; Borrow, Persephone; Williams, Kevin; Humphreys, Elizabeth; Afford, Simon; Adams, David H.; Bertoletti, Antonio; Maini, Mala K.

2007-01-01

143

Chemoprevention of a flavonoid fraction from Rhus verniciflua Stokes on aflatoxin B1-induced hepatic damage in mice.  

PubMed

Since aflatoxin B(1) (AFB(1))-mediated hepatic damage is related to the production of AFB(1)-8,9-epoxide and reactive oxygen species, bioactive compounds having antioxidant potentials are suggested to be capable of reducing AFB(1)-induced toxicity. We previously purified a mixture of flavonoids that we named RCMF (Rhus verniciflua Stokes chloroform-methanol fraction), from a traditional Korean food additive and herbal medicine. RCMF exhibited various biological effects, including antioxidant and antitumor activities. In this study, we examined whether RCMF protects against AFB(1)-induced liver injury using in vitro and in vivo systems. Pretreatment of HepG2 cells with RCMF significantly reduced AFB(1)-stimulated production of ROS and malondialdehyde (MDA) to the control levels. RCMF also prevented the reduction in HepG2 cell viability caused by AFB(1). Oral administration of RCMF to mice significantly suppressed an AFB(1)-induced increase in serum levels of alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. It also prevented MDA formation and blocked decreases in glutathione levels and superoxide dismutase activities in the livers of AFB(1)-treated mice. In addition, RCMF supplementation prevented an AFB(1) -induced decrease in serum titers of IgA and IgG1. Collectively, these results suggest that RCMF attenuates AFB(1)-mediated damage to the liver, and that this effect is at least partially related to the restoration of antioxidant defense systems and an increase in AFB(1)-GSH conjugate formation. PMID:20737424

Choi, Ki-Choon; Chung, Wan-Tae; Kwon, Jung-Kee; Jang, Yong-Suk; Yu, Ji-Yeon; Park, Seung-Moon; Lee, Jeong-Chae

2011-03-01

144

1,2-DIBROMOETHANE CAUSES RAT HEPATIC DNA DAMAGE AT LOW DOSES  

EPA Science Inventory

Two oral administrations of 1,2-dibromoethane to adult female rats at doses above 10 micromoles/kg (1.9 mg/kg) caused DNA damage as determined by the alkaline elution technique. Far greater doses (300 micromoles/kg, 56.4 mg/kg) of 1,2-dibromoethane were required to cause other he...

145

The influence of orexins on ethanol-induced behavioral sensitization in male mice.  

PubMed

Recent evidence indicates the involvement of orexin in reward circuitry and drug addiction. In the present study we evaluated the role of orexin in ethanol-induced behavioral sensitization. In the first experiment, Swiss male mice received seven administrations of saline or ethanol (2.2g/kg, i.p., chronic), every other day. On the last day of treatment, half of saline-treated mice received a saline injection (saline) whereas the other half received 2.2g/kg of ethanol (i.p., acute). Behavioral sensitization was assessed by locomotor activity tests and after the last one, immunoreactivity for orexin and Fos (ORX+Fos-ir) was assessed in the lateral hypothalamic area. Chronic ethanol treatment produced behavioral sensitization and a trend for greater ORX+Fos-ir. In the second experiment, mice were treated as in Experiment 1 and type 1 orexin receptor antagonist, SB334867 (20mg/kg), was administered before the ethanol challenge successfully blocking the expression of sensitization in mice chronically treated with EtOH. These results indicate that orexin plays a role in ethanol-induced behavioral sensitization. PMID:23880022

Macedo, Giovana Camila; Kawakami, Suzi Emiko; Vignoli, Thiago; Sinigaglia-Coimbra, Rita; Suchecki, Deborah

2013-09-13

146

Ethanol induces human red cell shape transformations and enhanced ligand-mediated agglutinability  

SciTech Connect

Ethanol concentrations are markedly elevated in rat stomach wall when ulcerogenic doses of 100 % ethanol (2 ml for 5 to 10 minutes) are instilled in rat gastric lumen. The authors observed that red cells in gastric mucosal postcapillary venules become spiculated and interadherent under these conditions. The authors have now studied this phenomenon in vitro using washing human red cells. Concentrations of high grade ethanol ranging from 2 to 10% (v/v) in physiological buffered saline (pH 7.3) without Ca/sup + +/ or Mg/sup + +/ at 25/sup 0/C rapidly transformed human red cells into spiculated forms. 2% ethanol transformed human red cells into disco-echinocytes in 15 min. whereas 10% ethanol transformed red blood cells into echinocytes within 3 min. Washing out of ethanol at 1 hour reverted the echinocytes into discocytes. However, following 3 hours of incubation in 10% ethanol washing out of ethanol produced stomatocytes. The ethanol-induced echinocytic shape transformations were accompanied by a dose-related increase in red cell agglutinability with poly-L-lysine or the plant lectin wheat germ agglutinin. The enhanced agglutinability was reversed by restoring the red cell shape changes and alterations in surface properties may play a role in the pathogenesis of ethanol-induced gastric ulcers.

Weinstein, R.S.; McLawhon, R.W.; Marikovsky, Y.

1986-03-01

147

In Vivo Antioxidant and Antiulcer Activity of Parkia speciosa Ethanolic Leaf Extract against Ethanol-Induced Gastric Ulcer in Rats  

PubMed Central

Background The current study was carried out to examine the gastroprotective effects of Parkia speciosa against ethanol-induced gastric mucosa injury in rats. Methodology/Principal Findings Sprague Dawley rats were separated into 7 groups. Groups 1–2 were orally challenged with carboxymethylcellulose (CMC); group 3 received 20 mg/kg omeprazole and groups 4–7 received 50, 100, 200 and 400 mg/kg of ethanolic leaf extract, respectively. After 1 h, CMC or absolute ethanol was given orally to groups 2–7. The rats were sacrificed after 1 h. Then, the injuries to the gastric mucosa were estimated through assessment of the gastric wall mucus, the gross appearance of ulcer areas, histology, immunohistochemistry and enzymatic assays. Group 2 exhibited significant mucosal injuries, with reduced gastric wall mucus and severe damage to the gastric mucosa, whereas reductions in mucosal injury were observed for groups 4–7. Groups 3–7 demonstrated a reversal in the decrease in Periodic acid-Schiff (PAS) staining induced by ethanol. No symptoms of toxicity or death were observed during the acute toxicity tests. Conclusion Treatment with the extract led to the upregulation of heat-shock protein 70 (HSP70) and the downregulation of the pro-apoptotic protein BAX. Significant increases in the levels of the antioxidant defense enzymes glutathione (GSH) and superoxide dismutase (SOD) in the gastric mucosal homogenate were observed, whereas that of a lipid peroxidation marker (MDA) was significantly decreased. Significance was defined as p<0.05 compared to the ulcer control group (Group 2).

Al Batran, Rami; Al-Bayaty, Fouad; Jamil Al-Obaidi, Mazen M.; Abdualkader, Abdualrahman Mohammed; Hadi, Hamid A.; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

2013-01-01

148

Evaluation of hepatoprotective potential of jigrine post-treatment against thioacetamide induced hepatic damage  

Microsoft Academic Search

Jigrine a polypharmaceutical herbal formulation containing aqueous extracts of 14 medicinal plants developed on the principles of unani system of medicine is used for liver ailments. The hepatoprotective potential of jigrine post-treatment at the dose of 0.5 ml\\/kg per day p.o. for 21 days was evaluated against thiocetamide induced liver damage in rats. Biochemical parameters like AST, ALT in serum

Aftab Ahmad; K. K Pillai; Abul K Najmi; Shibli J Ahmad; S. N Pal; D. K Balani

2002-01-01

149

Hepatoprotective Potential of Chestnut Bee Pollen on Carbon Tetrachloride-Induced Hepatic Damages in Rats  

PubMed Central

Bee pollen has been used as an apitherapy agent for several centuries to treat burns, wounds, gastrointestinal disorders, and various other diseases. The aim of our study was to investigate the hepatoprotective effects of chestnut bee pollen against carbon tetrachloride (CCI4)-induced liver damage. Total phenolic content, flavonoid, ferric reducing/antioxidant power, and DPPH radical activity measurements were used as antioxidant capacity determinants of the pollen. The study was conducted in rats as seven groups. Two different concentrations of chestnut bee pollens (200 and 400?mg/kg/day) were given orally and one group was administered with silibinin (50?mg/kg/day, i.p.) for seven days to the rats following the CCI4 treatment. The protective effect of the bee pollen was monitored by aspartate transaminase (AST) and alanine transaminase (AST) activities, histopathological imaging, and antioxidant parameters from the blood and liver samples of the rats. The results were compared with the silibinin-treated and untreated groups. We detected that CCI4 treatment induced liver damage and both the bee pollen and silibinin-treated groups reversed the damage; however, silibinin caused significant weight loss and mortality due, severe diarrhea in the rats. The chestnut pollen had showed 28.87?mg GAE/g DW of total phenolic substance, 8.07?mg QUE/g DW of total flavonoid, 92.71?mg Cyn-3-glu/kg DW of total anthocyanins, and 9?mg ?-carotene/100?g DW of total carotenoid and substantial amount of antioxidant power according to FRAP and DPPH activity. The results demonstrated that the chestnut bee pollen protects the hepatocytes from the oxidative stress and promotes the healing of the liver damage induced by CCI4 toxicity. Our findings suggest that chestnut bee pollen can be used as a safe alternative to the silibinin in the treatment of liver injuries.

Y?ld?z, Oktay; Can, Zehra; Saral, Ozlem; Yulug, Esin; Ozturk, Ferhat; Aliyaz?c?oglu, Rezzan; Canpolat, Sinan; Kolayl?, Sevgi

2013-01-01

150

Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats  

PubMed Central

Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which is associated with hepatocarcinogenesis. We investigated whether treatment with chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated hepatic carcinogenesis in rats. Rats were fed either an ethanol liquid diet or a non-ethanol liquid diet, with or without CMZ for one and ten months. A single intraperitoneal injection of diethylnitrosamine (DEN, 20 mg/kg) was given to initiate hepatic carcinogenesis. CYP2E1 expression, inflammatory proteins, cell proliferation, protein-bound 4-HNE, etheno-DNA adducts, 8-hydroxy-2'-deoxyguanosine (8-OHdG), retinoid concentrations, and hepatic carcinogenesis were examined. Ethanol feeding for 1 month with DEN resulted in significantly increased hepatic CYP2E1 levels and increased nuclear accumulation of NF-?B protein and TNF-? expression, which were associated with increased cyclin D1 expression and p-GST positive altered hepatic foci. All of these changes induced by ethanol feeding were significantly inhibited by the one month CMZ treatment. At 10-months of treatment, hepatocellular adenomas were detected in ethanol-fed rats only, but neither in control rats nor in animals receiving ethanol and CMZ. The 8-OHdG formation was found to be significantly increased in ethanol fed animals and normalized with CMZ treatment. In addition, alcohol-reduced hepatic retinol and retinoic acid concentrations were restored by CMZ treatment to normal levels in the rats at 10 months of treatment. These data demonstrate that the inhibition of ethanol-induced CYP2E1 as a key pathogenic factor can counteract the tumor-promoting action of ethanol by decreasing TNF-? expression, NF-?B activation, and oxidative DNA damage as well as restoring normal hepatic levels of retinoic acid in DEN-treated rats.

Ye, Qinyuan; Lian, Fuzhi; Chavez, Pollyanna R.G.; Chung, Jayong; Ling, Wenhua; Qin, Hua; Seitz, Helmut K.

2012-01-01

151

Biochemical evaluation of hepatic damage in subchronic exposure to malathion in rats: effect on superoxide dismutase and catalase activities using native PAGE.  

PubMed

The aim of this study was the evaluation of the hepatic damages following a subchronic exposure to malathion, an organophosphorus (OP) insecticide. Malathion was administered intragastrically in 1 ml corn oil containing 100 mg/kg Body Weight daily for 32 days. Malondialdehyde (MDA) concentration superoxide dismutase (SOD) and catalase (CAT) activities were analysed using a non-denaturing electrophoresis. The serum activities of Pseudocholinesterase (PchE), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were determined. Malathion exposure leads to a significant decrease in AchE activity, an increase in hepatic MDA, and in serum ASAT and ALAT activities. A positive correlation between serum transaminases levels and hepatic MDA was demonstrated. These results indicate that malathion exposure induced lipid peroxidation LPO, a process of degradation of membrane lipids, involving the deterioration of the cellular integrity. We have recorded a slight increase in antioxidant enzymes activities. This leads us to suggest an insufficient elimination of free radicals, causing cytotoxic effects. PMID:18722984

Rezg, Raja; Mornagui, Bessem; El-Fazaa, Saloua; Gharbi, Najoua

2008-09-01

152

Felodipine-and Ethanol-lnduced Gastric Mucosal Damage in Rats  

Microsoft Academic Search

Calcium channel blockers like verapamil have been shown to potentiate ethanol-induced gastric mucosal damage. However, the exact mechanism for this adverse drug interaction is still unknown. We used felodipine to study the ulcerogenic mechanisms of calcium channel blockers and the pathogenesis of ethanol-induced ulceration. The experiment was conducted in an ex vivo gastric chamber prepared in anesthetized animals. Felodipine (0.25,

X. G. Liu; C. H. Cho; J. K. S. Ko

1995-01-01

153

Hepatic tissue damage induced in Meriones ungliculatus due to infection with Babesia divergens-infected erythrocytes  

PubMed Central

Babesia divergens is an intraerythrocytic parasite which is capable of infecting a wide range of vertebrates causing huge economic losses. Histopathological, hematological and biochemical changes during B. divergens infection in female Meriones ungliculatus were reported. Animals were challenged with 5 × 106B. divergens-infected erythrocytes. Parasitemia were maximum at day 5 postinfection where all gerbils died. Infection of gerbils with Babesia induced a significant decrease in erythrocytic count as well as the hemoglobin concentration and hematocrit percentage but leucocytes were increased significantly when compared to uninfected gerbils. Liver enzymes aspartate aminotransferase (AST) and aniline aminotransferase (ALT) were significantly increased while albumin and total bilirubin were significantly decreased at day 5 postinfection with B. divergens-infected erythrocytes. Histopathological scores of inflammation after infection of gerbils were done using Ischak’s activity index and indicated that the liver was severely affected. In conclusion, the study indicated that the course of infection by B. divergens-induced alternations in hematology, biochemistry and histopathology of the hepatic tissue.

Dkhil, M.A.; AL-Quraishy, S.; Abdel-Baki, A.S.

2010-01-01

154

Hepatitis C virus and metabolic disorder interactions towards liver damage and atherosclerosis.  

PubMed

Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a "viral" steatosis which is frequently superimposed to a "metabolic" one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed. PMID:24659875

Vespasiani-Gentilucci, Umberto; Gallo, Paolo; De Vincentis, Antonio; Galati, Giovanni; Picardi, Antonio

2014-03-21

155

Pinus massoniana bark extract protects against oxidative damage in L-02 hepatic cells and mice.  

PubMed

The hepatoprotective activity of Pinus massoniana bark extract (PMBE) against hydrogen peroxide (H2O2)-induced damage in normal human liver L-02 cells and carbon tetrachloride (CCl4)-induced acute hepatotoxicity in mice was investigated. The L-02 cells were pre-treated with PMBE for 24 hours prior to exposure to 0.5 mM H2O2 for 3 or 24 hours. The cell viability, level of malondialdehyde (MDA) and glutathione (GSH), and the catalase (CAT) activity were evaluated. For in vivo experiments, mice were divided into groups and PMBE administered orally, after which each group was assigned a further treatment. Histopathological examination, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and GSH, the liver tissue levels of MDA and GSH, the activities of CAT and glutathione peroxidase (GSH-Px), were evaluated. PMBE treatment decreased the level of MDA and increased the cell viability, GSH content and CAT activity in H2O2 treated L-02 cells treated for 3 hours. PMBE obviously decreased serum ALT, AST, ALP, and liver tissue MDA, while increasing serum GSH, and liver tissue CAT and GSH-Px activities. In conclusion, PMBE treatment prevents H2O2 and CCl4-induced liver damage, and therefore could have a potential clinical usage. PMID:20821822

Wang, Mei; Ma, Hong-Ling; Liu, Bing; Wang, Hong-Bin; Xie, Heng; Li, Ruo-Da; Wang, Jin-Fa

2010-01-01

156

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity  

Microsoft Academic Search

The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy-proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg\\/m2), distribution of body fat, HCV genotype, and levels

Luigi E. Adinolfi; Michele Gambardella; Augusto Andreana; Marie-françoise Tripodi; Riccardo Utili; Giuseppe Ruggiero

2001-01-01

157

Hepatic protection by noni fruit juice against CCl(4)-induced chronic liver damage in female SD rats.  

PubMed

Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI Juice (TNJ) against CCl(4)-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control, placebo and TNJ (6 mL/rat/day) groups. On day 15, animals in the placebo and TNJ groups received 0.25 mL/kg CCl(4) in corn oil once a week for 12 successive weeks. All animals were sacrificed at week 16. Blood and liver were collected for liver function, lipid panel tests, and histological observation. Histopathological examination revealed that liver sections from the TNJ + CCl(4) appeared similar to controls, whereas typical hepatic steatosis was observed in the placebo + CCl(4) group. Serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels were increased in the placebo group compared with the TNJ group. In contrast, high-density lipoprotein (HDL) was increased in the TNJ group and decreased in the placebo group. Thus, TNJ juice appears to protect the liver from chronic exogenous CCl(4) exposures. Such protective mechanisms are supportive evidence for the utility of noni in traditional medicine for liver ailments. PMID:18654853

Wang, Mian-Ying; Anderson, Gary; Nowicki, Diane; Jensen, Jarakae

2008-09-01

158

Two Case Reports of Life-Threatening Ethanol-Induced Anaphylaxis  

PubMed Central

Adverse reactions to alcoholic beverages are common and diverse in aetiology. Ethanol-induced anaphylaxis, however, is a rare but often life-threatening condition that warrants careful evaluation in suspected individuals. We present the cases of two patients who developed urticaria, angioedema and throat constriction within minutes of consuming white wine. Both individuals demonstrated no adverse reaction to double-blind placebo-controlled challenges to metabisulphite or sodium salicylate. However, an open challenge to white wine elicited urticaria in both subjects. This reaction was reproduced with a double-blind placebo-controlled challenge to ethanol and was accompanied by a rise in serum total tryptase levels. Positive skin test responses to 2% acetic acid, a breakdown product of ethanol, were elicited from both patients but not from three normal controls. These two cases demonstrate the need for a systematic approach for the evaluation of allergic reactions to alcohol.

Fernando, S.L.; Clarke, L.R.

2009-01-01

159

Pycnogenol and vitamin E inhibit ethanol-induced apoptosis in rat cerebellar granule cells.  

PubMed

Pycnogenol (PYC), a patented combination of bioflavonoids extracted from the bark of French maritime pine (Pinus maritima), scavenges free radicals and promotes cellular health. The protective capacity of PYC against ethanol toxicity of neurons has not previously been explored. The present study demonstrates that in postnatal day 9 (P9) rat cerebellar granule cells the antioxidants vitamin E (VE) and PYC (1) dose dependently block cell death following 400, 800, and 1600 mg/dL ethanol exposure (2) inhibit the ethanol-induced activation of caspase-3 in the same model system; and (3) reduce neuronal membrane disruption as assayed by phosphatidylserine translocation to the cell surface. These results suggest that both PYC and VE have the potential to act as therapeutic agents, antagonizing the induction of neuronal cell death by ethanol exposure. PMID:15146544

Siler-Marsiglio, Kendra I; Shaw, Gerry; Heaton, Marieta B

2004-06-01

160

Protection from ethanol-induced limb malformations by the superoxide dismutase/catalase mimetic, EUK-134.  

PubMed

Based on previous in vitro studies that have illustrated prevention of ethanol-induced cell death by antioxidants, using an in vivo model, we have tested the anti-teratogenic potential of a potent synthetic superoxide dismutase plus catalase mimetic, EUK-134. The developing limb of C57BL/6J mice, which is sensitive to ethanol-induced reduction defects, served as the model system. On their ninth day of pregnancy, C57BL/6J mice were administered ethanol (two intraperitoneal doses of 2.9 g/kg given 4 h apart) alone or in combination with EUK-134 (two doses of 10 mg/kg). Pregnant control mice were similarly treated with either vehicle or EUK-134, alone. Within 15 h of the initial ethanol exposure, excessive apoptotic cell death was observed in the apical ectodermal ridge (AER) of the newly forming forelimb buds. Forelimb defects, including postaxial ectrodactyly, metacarpal, and ulnar deficiencies, occurred in 67.3% of the ethanol-exposed fetuses that were examined at 18 days of gestation. The right forelimbs were preferentially affected. No limb malformations were observed in control fetuses. Cell death in the AER of embryos concurrently exposed to ethanol and EUK-134 was notably reduced compared with that in embryos from ethanol-treated dams. Additionally, the antioxidant treatment reduced the incidence of forelimb malformations to 35.9%. This work illustrates that antioxidants can significantly improve the adverse developmental outcome that results from ethanol exposure in utero, diminishing the incidence and severity of major malformations that result from exposure to this important human teratogen. PMID:15208273

Chen, Shao-Yu; Dehart, Deborah B; Sulik, Kathleen K

2004-08-01

161

Expression of Ethanol-Induced Behavioral Sensitization Is Associated with Alteration of Chromatin Remodeling in Mice  

PubMed Central

Background Ethanol-induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of addiction. EIBS does not occur uniformly in all animals even from the same inbred strain. Since recent data demonstrate that epigenetic mechanisms are likely to be involved in the development and the persistence of ethanol-related behaviors, we explored the involvement of epigenetic mechanisms in ethanol response after EIBS development. Methodology DBA/2J mice were i.p. injected with saline or ethanol (2 g/kg) once a day for 10 consecutive days. At day 17, ethanol-treated mice were split in resistant and sensitized groups. Brains were then removed 30 min after a saline or 2 g/kg ethanol challenge to assess i) gene expression using PCR array targeting 84 epigenetic-related genes and ii) histone deacetylases (HDAC), histone acetylases (HAT) and DNA methyltransferases (DNMT) activities as well as H4K12 acetylation. Principal Findings Acute ethanol administration decreased dnmt1, esco2 and rps6ka5 genes expression. These genes were similarly altered in sensitized but not in resistant mice after an ethanol challenge, suggesting that resistant mice were tolerant to the transcriptional outcomes of an ethanol challenge. Whereas global HAT or DNMT activity was not affected, global HDAC activity was reduced after an acute ethanol injection. HDAC inhibition occurred in all ethanol-treated mice but with a lesser extent in sensitized animals. As a consequence, H4 acetylation was specifically potentiated in the core of the Nac proportionally to the striatal HDAC activity decrease. Conclusions/Significance The present study highlights that the contrasted behavioral response to an ethanol challenge between resistant and sensitized mice may be mediated by epigenetic mechanisms occurring specifically in the striatum. Here we show that vulnerability to ethanol dependence and relapse could be, at least in part, due to individual variability in acute ethanol-induced epigenetic response.

Alaux-Cantin, Stephanie; Naassila, Mickael

2012-01-01

162

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

PubMed

The quaternary benzo[c]phenanthridine alkaloid, chelerythrine (CHE), is of great practical and research interest because of its pronounced, widespread physiological effects, primarily antimicrobial and anti-inflammatory, arising from its ability to interact with proteins and DNA. Although CHE was originally shown to possess anti-inflammatory properties, its effects on acute gastric ulcer have not been previously explored. The aim of the present study is to evaluate the protective effect of CHE on ethanol induced gastric ulcer in mice. Administration of CHE at doses of 1, 5 and 10mg/kg bodyweight prior to ethanol ingestion dose-dependently inhibited gastric ulcer. The gastric mucosal lesion was assessed by ulcer area, gastric juice acidity, myeloperoxidase (MPO) activities, macroscopic and histopathological examinations. CHE significantly reduced the gastric ulcer index, myeloperoxidase activities, macroscopic and histological score in a dose-dependent manner. In addition, CHE also significantly inhibited nitric oxide (NO) concentration, pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-?) level in serum and gastric mucosal in the mice exposed to ethanol induced ulceration in a dose-dependent manner. In addition, immunohistochemical analysis revealed that CHE markedly attenuated the overexpression of nuclear factor-?B in gastric mucosa of mice. It was concluded that CHE represents a potential therapeutic option to reduce the risk of gastric ulceration. In addition, acute toxicity study revealed no abnormal sign to the mice treated with CHE (15mg/kg). These findings suggest that the gastroprotective activity of CHE might contribute in adjusting the inflammatory cytokine by regulating the NF-?B signalling pathway. PMID:24300194

Li, Wei-Feng; Hao, Ding-Jun; Fan, Ting; Huang, Hui-Min; Yao, Huan; Niu, Xiao-Feng

2014-02-01

163

LIMB DEFECTS INDUCED BY RETINOIC ACID SIGNALING ANTAGONISM AND SYNTHESIS INHIBITION ARE CONSISTENT WITH ETHANOL-INDUCED LIMB DEFECTS  

EPA Science Inventory

Limb defects induced by retinoic acid signaling antagonism and synthesis inhibition are consistent with ethanol-induced limb defects Johnson CS1, Sulik KK1,2, Hunter, ES III3 1Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, NC....

164

SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER  

EPA Science Inventory

The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

165

Eat more carrots? Dampening cell death in ethanol-induced liver fibrosis by ?-carotene  

PubMed Central

Alcoholic liver disease (ALD) represents one of the principal causes of liver damage in humans. Long-term ethanol abuse leads to progressive liver injury and tissue remodeling, including steatosis, inflammation, fibrosis, cirrhosis and increased risk for hepatocellular carcinoma (HCC) development. Oxidative stress and subsequent liver cell death has long been identified as one of the key mechanisms during ALD progression, therefore antioxidants may display promising treatment options. In this issue of Hepatobiliary Surgery and Nutrition (HBSN), Peng et al. demonstrate that oral supplementation with ?-carotene during chronic ethanol feeding in rats reduces oxidative stress, apoptotic cell death and inflammation. Reducing hepatocyte apoptosis, a major trigger for fibrogenesis and tumorigenesis, would make ?-carotene a prospective target for treatment. However, before translating the promising findings of Peng and colleagues into clinical scenarios, it needs to be determined which cell death pathways, including necrosis and necroptosis, are affected by ?-carotene, which liver cell populations are targeted by this vitamin A precursor, how specific the effects are for ALD in comparison to non-alcoholic steatohepatitis (NASH) or other chronic liver diseases, and whether reduced hepatic oxidative stress and apoptosis upon ?-carotene supplementation truly relate to beneficial long-term consequences with respect to fibrosis, cirrhosis or HCC development.

Hammerich, Linda

2013-01-01

166

Cyanidin-3-Glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2  

PubMed Central

Background Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion. Results C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7ErbB2) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130Cas, as well as interactions among these proteins. C3G abolished ethanol-mediated p130Cas/JNK interaction. Conclusions C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

2010-01-01

167

Cytisine modulates chronic voluntary ethanol consumption and ethanol-induced striatal up-regulation of ?FosB in mice.  

PubMed

Chronic administration of ethanol induces persistent accumulation of ?FosB, an important transcription factor, in the midbrain dopamine system. This process underlies the progression to addiction. Previously, we have shown that cytisine, a neuronal nicotinic acetylcholine receptor (nAChR) partial agonist, reduces various ethanol-drinking behaviors and ethanol-induced striatal dopamine function. However, the effects of cytisine on chronic ethanol drinking and ethanol-induced up-regulation of striatal ?FosB are not known. Therefore, we examined the effects of cytisine on chronic voluntary ethanol consumption and associated striatal ?FosB up-regulation in C57BL/6J mice using behavioral and biochemical methods. Following the chronic voluntary consumption of 15% (v/v) ethanol under a 24-h two-bottle choice intermittent access (IA; 3 sessions/week) or continuous access (CA; 24 h/d and 7 d/week) paradigm, mice received repeated intraperitoneal injections of saline or cytisine (0.5 or 3.0 mg/kg). Ethanol and water intake were monitored for 24 h post-treatment. Pretreatment with cytisine (0.5 or 1.5 mg/kg) significantly reduced ethanol consumption and preference in both paradigms at 2 h and 24 h post-treatment. The ?FosB levels in the ventral and dorsal striatum were determined by Western blotting 18-24 h after the last point of ethanol access. In addition, cytisine (0.5 mg/kg) significantly attenuated up-regulation of ?FosB in the ventral and dorsal striatum following chronic ethanol consumption in IA and CA paradigms. The results indicate that cytisine modulates chronic voluntary ethanol consumption and reduces ethanol-induced up-regulation of striatal ?FosB. Further, the data suggest a critical role of nAChRs in chronic ethanol-induced neurochemical adaptations associated with ethanol addiction. PMID:23601929

Sajja, Ravi Kiran; Rahman, Shafiqur

2013-06-01

168

Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats.  

PubMed

Diabetes mellitus is the most common serious metabolic disorder and it is considered to be one of the five leading causes of death in the world. Hyperglycemia-mediated oxidative stress plays a crucial role in diabetic complications. Hence, this study was undertaken to evaluate the protective effect of esculetin on the plasma glucose, insulin levels, tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. Extent of oxidative stress was assessed by the elevation in the levels of lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD); reduction in the enzymic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST); nonenzymic antioxidants Vitamin C, E and reduced glutathione (GSH) were observed in the liver and kidney tissues of diabetic control rats as compared to control rats. Oral supplementation of esculetin to diabetic rats for 45 days significantly brought back lipid peroxidation markers, enzymic and nonenzymic antioxidants to near normalcy. Moreover, the histological observations evidenced that esculetin effectively rescues the hepatocytes and kidney from hyperglycemia mediated oxidative damage without affecting its cellular function and structural integrity. These findings suggest that esculetin (40 mg/kg BW) treatment exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic and renal tissues. Further, detailed studies are in progress to elucidate the molecular mechanism by which esculetin elicits its modulatory effects in insulin signaling pathway. PMID:23079336

Prabakaran, Dhamodaran; Ashokkumar, Natarajan

2013-02-01

169

Relating the liver damage with hepatitis C virus polymorphism in core region and human variables in HIV1-coinfected patients  

Microsoft Academic Search

Hepatitis C virus (HCV) infection is the most important cause of chronic hepatitis, cirrhosis and end-stage liver disease leading to liver transplantation worldwide. Chronic infection by HCV causes liver fibrosis, which is accelerated by unknown mechanisms in patients with human immunodeficiency virus-1 (HIV-1) coinfection. Although the genetic variability of both HCV and HIV has been extensively studied in the context

Marina Matas; Antňnia Picornell; Carmen Cifuentes; Antoni Payeras; Antoni Bassa; Francesc Homar; F. Xavier López-Labrador; Andrés Moya; Maria M. Ramon; José A. Castro

2010-01-01

170

Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism  

Microsoft Academic Search

AIM: To investigate the inhibitive effect and its possible mechanism of Cordyceps Sinensis (CS) on CCl4-plus ethanol- induced hepatic fibrogenesis in experimental rats. METHODS: Rats were randomly allocated into a normal control group, a model control group and a CS group. The latter two groups were administered with CCl4 and ethanol solution at the beginning of the experiment to induce

Yu-Kan Liu; Wei Shen

2003-01-01

171

Ethanol-Induced Activation of ATP-Dependent Proton Extrusion in Elodea densa Leaves.  

PubMed

In Elodea densa leaves, ethanol up to 0.17 m stimulates H(+) extrusion activity. This effect is strictly dependent on the presence of K(+) in the medium and is suppressed by the presence of the plasmalemma H(+)-ATPase inhibitor vanadate. Stimulation of H(+) extrusion is associated with (a) a decrease in cellular ATP level, (b) a marked hyperpolarization of transmembrane electrical potential, and (c) an increase in net K(+) influx. These results suggest that ethanol-induced H(+) extrusion is mediated by an activation of the plasma membrane ATP-dependent, electrogenic proton pump. This stimulating effect is associated with an increase of cell sap pH and of the capacity to take up the weak acid 5,5-dimethyloxazolidine-2,4-dione, which is interpretable as due to an increase of cytosolic pH. This indicates that the stimulation of H(+) extrusion by ethanol does not depend on a cytosolic acidification by products of ethanol metabolism. The similarity of the effects of ethanol and those of photosynthesis on proton pump activity in E. densa leaves suggests that a common metabolic situation is responsible for the activation of the ATP-dependent H(+)-extruding mechanism. PMID:16653093

Marrč, M T; Venegoni, A; Moroni, A

1992-11-01

172

Acute Ethanol-Induced Changes in Edema and Metabolite Concentrations in Rat Brain  

PubMed Central

The aim of this study is to describe the acute effects of EtOH on brain edema and cerebral metabolites, using diffusion weight imaging (DWI) and proton magnetic resonance spectroscopy (1H-MRS) at a 7.0T MR and to define changes in apparent diffusion coefficient (ADC) values and the concentration of metabolites in the rat brain after acute EtOH intoxication. ADC values in each ROI decreased significantly at 1 h and 3 h after ethanol administration. ADC values in frontal lobe were decreased significantly compared with other regions at 3 h. For EtOH/Cr+PCr and cerebral metabolites (Cho, Tau, and Glu) differing over time, no significant differences for Ins, NAA, and Cr were observed in frontal lobes. Regression analysis revealed a significant association between TSEtOH/Cr+PCr and TSCho, TSTau, TSGlu, and TSADC. The changes of ADC values in different brain regions reflect the process of the cytotoxic edema in vivo. The characterization of frontal lobes metabolites changes and the correlations between TSEtOH/Cr+PCr and TSCho, TSTau, and TSGlu provide a better understanding for the biological mechanisms in neurotoxic effects of EtOH on the brain. In addition, the correlations between TSEtOH/Cr+PCr and TSADC will help us to understand development of the ethanol-induced brain cytotoxic edema.

Liu, Huimin; Yan, Gen; Liu, Baoguo; Kong, Lingmei; Ding, Yan; Tan, Hui; Zhang, Guishan

2014-01-01

173

Ethanol-induced activation of adenine nucleotide turnover. Evidence for a role of acetate  

SciTech Connect

Consumption of alcohol causes hyperuricemia by decreasing urate excretion and increasing its production. Our previous studies indicate that ethanol administration increases uric acid production by increasing ATP degradation to uric acid precursors. To test the hypothesis that ethanol-induced increased urate production results from acetate metabolism and enhanced adenosine triphosphate turnover, we gave intravenous sodium acetate, sodium chloride and ethanol (0.1 mmol/kg per min for 1 h) to five normal subjects. Acetate plasma levels increased from 0.04 +/- 0.01 mM (mean +/- SE) to peak values of 0.35 +/- 0.07 mM and to 0.08 +/- 0.01 mM during acetate and ethanol infusions, respectively. Urinary oxypurines increased to 223 +/- 13% and 316 +/- 44% of the base-line values during acetate and ethanol infusions, respectively. Urinary radioactivity from the adenine nucleotide pool labeled with (8-14C) adenine increased to 171 +/- 27% and to 128 +/- 8% of the base-line values after acetate and ethanol infusions. These data indicate that both ethanol and acetate increase purine nucleotide degradation by enhancing the turnover of the adenine nucleotide pool. They support the hypothesis that acetate metabolism contributes to the increased production of urate associated with ethanol intake.

Puig, J.G.; Fox, I.H.

1984-09-01

174

Gastric histamine content and ulcer formation in rats with ethanol-induced injury. Effects of cinnarizine and flunarizine  

Microsoft Academic Search

The effects of the calcium antagonists cinnarizine and flunarizine on gastric histamine content and ulcer formation in rats with ethanol-induced injury were studied. Gastric ulcers were inflicted by oral application of 50% or 100% ethanol solution. Cinnarizine (20 mg\\/kg), flunarizine (10 mg\\/kg) and cimetidine (100 mg\\/kg) were administered orally 1 h before ethanol. Histamine was assayed fluorometrically. No effect of

V. Lozeva; K. Marazova; A. Belcheva

1994-01-01

175

Banhabaekchulchunma-tang, a traditional herbal formula attenuates absolute ethanol-induced gastric injury by enhancing the antioxidant status  

PubMed Central

Background Banhabaekchulchunma-tang (hange-byakujutsu-tenma-to in Japanese and banxia-baizhu-tianma-tang in Chinese) is a mixture of fourteen herbs. It is used traditionally for the treatment of anemia, anorexia, general weakness, and female infertility in China, Japan, and Korea. In this study, we investigated the protective effects of a Banhabaekchulchunma-tang water extract (BCT) against ethanol-induced acute gastric injury in rats. Methods Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the BCT group were given oral doses of omeprazole (50 mg/kg) or BCT (400 mg/kg), respectively, 2 h prior to the administration of absolute ethanol. The stomach of each animal was excised and examined for gastric mucosal lesions. To confirm the protective effects of BCT, we evaluated the degree of lipid peroxidation, the level of reduced glutathione (GSH), and the activities of the antioxidant enzymes catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase in the stomach. In addition, we conducted an acute toxicity study to evaluate the safety of BCT according to OECD guideline. Results BCT reduced ethanol-induced hemorrhage, hyperemia, and loss of epithelial cell in the gastric mucosa. BCT reduced the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, and increased the mucosal GSH content and the activities of antioxidant enzymes. In addition, BCT did not cause any adverse effects at up to 5000 mg/kg. Conclusions These results indicate that BCT protects the gastric mucosa against ethanol-induced gastric injury by increasing the antioxidant status. We suggest that BCT could be developed as an effective drug for the treatment of gastric injury caused by alcohol intake.

2013-01-01

176

The Ethanol-Induced Stimulation of Rat Duodenal Mucosal Bicarbonate Secretion In Vivo Is Critically Dependent on Luminal Cl–  

PubMed Central

Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ?30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl? from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl? and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

Sommansson, Anna; Wan Saudi, Wan Salman; Nylander, Olof; Sjoblom, Markus

2014-01-01

177

Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice  

Microsoft Academic Search

To find out the active principles against ethanol-induced toxicity in mice, Andrographis paniculata Nees. (Ap) was chosen and isolated andrographolide (ANDRO) and arabinogalactan proteins (AGPs). ANDRO was detected by HPTLC, FTIR and quantified by HPLC (10mg\\/g of Ap powder). AGPs was detected by ?-glucosyl Yariv staining of SDS-PAGE gel, FTIR and quantified by single radial gel diffusion assay with ?-glucosyl

Prajjal K. Singha; Somenath Roy; Satyahari Dey

2007-01-01

178

Adult Neuronal Arf6 Controls Ethanol-Induced Behavior With Arfaptin Downstream of Rac1 and RhoGAP18B  

PubMed Central

Alcohol use disorders affect millions of individuals. However, the genes and signaling pathways involved in behavioral ethanol responses and addiction are poorly understood. Here we identify a conserved biochemical pathway that underlies the sedating effects of ethanol in Drosophila. Mutations in the Arf6 small GTPase signaling pathway cause hypersensitivity to ethanol-induced sedation. We show that Arf6 functions in the adult nervous system to control ethanol-induced behavior. We also find that the Drosophila Arfaptin protein directly binds to the activated forms of Arf6 and Rac1 GTPases, and mutants in Arfaptin also display ethanol-sensitivity. Arf6 acts downstream of Rac1 and Arfaptin to regulate ethanol-induced behaviors, and we thus demonstrate that this conserved Rac1/Arfaptin/Arf6 pathway is a major mediator of ethanol-induced behavioral responses.

Peru y Colon de Portugal, Raniero L.; Acevedo, Summer F.; Rodan, Aylin R.; Chang, Leo Y.; Eaton, Benjamin A.; Rothenfluh, Adrian

2012-01-01

179

Serum HCV RNA Levels Correlate with Histological Liver Damage and Concur with Steatosis in Progression of Chronic Hepatitis C  

Microsoft Academic Search

The role of HCV RNA levels and host factors in the severity of liver injury was studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH) C patients (179 men; median age: 52 years, range 19–68; CH, 198; cirrhosis, 100) and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b, 53%; 2a\\/c, 28%; 3a, 7%; 4,

Luigi E. Adinolfi; Riccardo Utili; Augusto Andreana; Marie-Francoise Tripodi; Marta Marracino; Michele Gambardella; Mariagrazia Giordano; Giuseppe Ruggiero

2001-01-01

180

Activation of autophagy by globular adiponectin attenuates ethanol-induced apoptosis in HepG2 cells: involvement of AMPK/FoxO3A axis.  

PubMed

Hepatocellular apoptosis is an important pathological entity of alcoholic liver disease. Previously, we have shown that globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis by modulating an array of signaling pathways. In the present study, we investigated the role of autophagy induction by gAcrp in the suppression of ethanol-induced apoptosis and its potential mechanism(s) in liver cells. Here, we demonstrated that gAcrp significantly restores ethanol-induced suppression of autophagy-related genes, including Beclin-1 and microtubule-associated protein light chain (LC3B) both in primary rat hepatocytes and human hepatoma cell line (HepG2). Globular adiponectin also restored autophagosome formation suppressed by ethanol treatment in HepG2. Furthermore, inhibition of gAcrp-induced autophagic process by knock-down of LC3B prevented protection from ethanol-induced apoptosis. In particular, the autophagic process induced by gAcrp was involved in the suppression of ethanol-induced activation of caspase-8 and expression of Bax. Moreover, knock-down of AMPK by small interfering RNA (siRNA) blocked gAcrp-induced expression of genes related to autophagy, which in turn prevented protection from ethanol-induced apoptosis, suggesting that AMPK plays an important role in the induction of autophagy and protection of liver cells by gAcrp. Finally, we also showed that gAcrp treatment induces translocation of the forkhead box O member protein, FoxO3A, into the nucleus, which may play a role in the induction of autophagy-related genes. Taken together, our data demonstrated that gAcrp protects liver cells from ethanol-induced apoptosis via induction of autophagy. Further, the AMPK-FoxO3A axis plays a cardinal role in gAcrp-induced autophagy and subsequent inhibition of ethanol-induced apoptosis. PMID:23688633

Nepal, Saroj; Park, Pil-Hoon

2013-10-01

181

Oxidative stress mediated toxicity exerted by ethanol-inducible CYP2E1  

SciTech Connect

Induction of CYP2E1 by ethanol is one of the central pathways by which ethanol generates a state of oxidative stress in hepatocytes. To study the biochemical and toxicological actions of CYP2E1, our laboratory established HepG2 cell lines which constitutively overexpress CYP2E1 and characterized these cells with respect to ethanol toxicity. Addition of ethanol or an unsaturated fatty acid such as arachidonic acid or iron was toxic to the CYP2E1-expressing cells but not control cells. This toxicity was associated with elevated lipid peroxidation and could be prevented by antioxidants and inhibitors of CYP2E1. Apoptosis occurred in the CYP2E1-expressing cells exposed to ethanol, arachidonic acid, or iron. Removal of GSH caused a loss of viability in the CYP2E1-expressing cells even in the absence of added toxin or pro-oxidant. This was associated with mitochondrial damage and decreased mitochondrial membrane potential. Low concentrations of iron and arachidonic acid synergistically interacted with CYP2E1 to produce cell toxicity, suggesting these nutrients may act as priming or sensitizing agents to alcohol-induced liver injury. Surprisingly, CYP2E1-expressing cells had elevated GSH levels, due to transcriptional activation of glutamate cysteine ligase. Similarly, levels of catalase, alpha-, and microsomal glutathione transferase were also increased, suggesting that upregulation of these antioxidant genes may reflect an adaptive mechanism to remove CYP2E1-derived oxidants. Using co-cultures, interaction between CYP2E1-derived diffusible mediators to activate collagen production in hepatic stellate cells was found. While it is likely that several mechanisms contribute to alcohol-induced liver injury, the linkage between CYP2E1-dependent oxidative stress, mitochondrial injury, stellate cell activation, and GSH homeostasis may contribute to the toxic action of ethanol on the liver. HepG2 cell lines overexpressing CYP2E1 may be a valuable model to characterize the biochemical and toxicological properties of CYP2E1.

Wu Defeng [Department of Pharmacology and Biological Chemistry, Box 1603, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 (United States); Cederbaum, Arthur I. [Department of Pharmacology and Biological Chemistry, Box 1603, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029 (United States)]. E-mail: arthur.cederbaum@mssm.edu

2005-09-01

182

The effect of curcumin on ethanol induced changes in suprachiasmatic nucleus (SCN) and pineal.  

PubMed

(1) Circadian clocks have been localized to discrete sites within the nervous system of several organisms and in mammals to the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN controls and regulates the production and discharge of melatonin (hormonal message of darkness) from the pineal gland via a multisynaptic efferent pathway. The nocturnal rise in melatonin production from serotonin results due to an increased activity of serotonin N-acetyl transferase (NAT). (2) The complex interaction between alcohol and biological clock need to be understood as alcoholism results in various clock linked neuronal disorders especially loss of memory and amnesia like state of consciousness, sleep disorders, insomnia, dementia etc. (3) Serotonin, 5-Hydroxy-tryptamine (5-HT) plays an important role in mediating alcohol's effects on the brain. Understanding the impact of alcohol consumption on circadian system is a pre-requisite to help in treatment of alcohol induced neurological disorders. We, therefore, studied the effect of ethanol drinking and ethanol withdrawal on daily rhythms of serotonin and its metabolite, 5-hydroxy-indole acetic acid (5-HIAA) in SCN and Pineal of adult male Wistar rats maintained under light-dark (LD, 12:12) conditions. (4) Curcumin is well known for its protective properties such as antioxidant, anti-carcinogenic, anti-viral and anti-infectious etc. Hence, we studied the effect of curcumin on ethanol induced changes on 5-HT and 5-HIAA levels and rhythms in SCN and Pineal. (5) Ethanol withdrawal could not restore either rhythmicity or phases or levels of 5-HT and 5-HIAA. Curcumin administration resulted in partial restoration of daily 5-HT/5-HIAA ratio, with phase shifts in SCN and in Pineal. Understanding the impact of alcohol consumption on circadian system and the role of herbal medication on alcohol withdrawal will help in treatment of alcohol induced neurological disorders. PMID:17846884

Jagota, Anita; Reddy, M Y

2007-12-01

183

Protective and therapeutic effects of Argyreia speciosa against ethanol-induced gastric ulcer in rats.  

PubMed

The protective and therapeutic effects of Argyreia speciosa Sweet (Convolvulaceae) against ethanol-induced gastric ulcer in rats were evaluated. Ethanolic and water extracts of the aerial plant parts (200 mg/kg body weight) were orally administered daily for seven days prior to or after ulceration with one oral dose of 1 mL absolute ethanol on 24-h empty stomachs. Rats were divided into eleven groups. Group 1 served as control. To groups 2 and 3 each extract was administered. Groups 4 to 6 received each extract or ranitidine (100 mg/kg body weight) prior to ulcer induction. Groups 7 to 9 received each extract or ranitidine post ulcer induction. Groups 10 and 11 were gastric ulcerative rats after one hour and one week of ethanol induction. The evaluation was done through measuring ulcer indices: stomach acidity and volume, lesion counts, mucus, and prostaglandin E2 contents. Oxidative stress marker, i. e. malondialdehyde, glutathione, and superoxide dismutase, were estimated. Certain marker enzymes for different cell organelles, i. e. succinate and lactate dehydrogenases, glucose-6-phosphatase, acid phosphatase, and 5'-nucleotidase, were evaluated. The work was extended to determine the collagen content and the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index, antioxidant levels, collagen content, and the marker enzymes. The water extract attenuated these increments and was more potent as a protective agent, while the ethanol extract exhibited stronger therapeutic potency. In conclusion, A. speciosa acted as antiulcer agent. More detailed studies are required to identify the compounds responsible for the pharmacological effect. PMID:22486041

Motawi, Tarek K; Hamed, Manal A; Hashem, Reem M; Shabana, Manal H; Ahmed, Yomna R

2012-01-01

184

Deficiency in AMPK attenuates ethanol-induced cardiac contractile dysfunction through inhibition of autophagosome formation  

PubMed Central

Aims Binge drinking often triggers compromised myocardial contractile function while activating AMP-activated protein kinase (AMPK). Given the role of AMPK in the initiation of autophagy through the mammalian target of rapamycin complex 1 (mTORC1) and Unc51-like kinase (ULK1), this study was designed to examine the impact of AMPK deficiency on cardiac function and the mechanism involved with a focus on autophagy following an acute ethanol challenge. Methods and results Wild-type (WT) and transgenic mice overexpressing a kinase-dead (KD) ?2 isoform (K45R mutation) of AMPK were challenged with ethanol. Glucose tolerance, echocardiography, Langendorff heart and cardiomyocyte contractile function, autophagy, and autophagic signalling including AMPK, acetyl-CoA carboxylase (ACC), mTOR, the mTORC1-associated protein Raptor, and ULK1 were examined. Ethanol exposure triggered glucose intolerance and compromised cardiac contraction accompanied by increased phosphorylation of AMPK and ACC as well as autophagosome accumulation (increased LC3II and p62), the effects of which were attenuated or mitigated by AMPK deficiency or inhibition. Ethanol dampened and stimulated, respectively, the phosphorylation of mTOR and Raptor, the effects of which were abolished by AMPK deficiency. ULK1 phosphorylation at Ser757 and Ser777 was down-regulated and up-regulated, respectively, by ethanol, the effect of which was nullified by AMPK deficiency or inhibition. Moreover, the ethanol challenge enhanced LC3 puncta in H9c2 cells and promoted cardiac contractile dysfunction, and these effects were ablated by the inhibition of autophagy or AMPK. Lysosomal inhibition failed to accentuate ethanol-induced increases in LC3II and p62. Conclusion In summary, these data suggest that ethanol exposure may trigger myocardial dysfunction through a mechanism associated with AMPK-mTORC1-ULK1-mediated autophagy.

Guo, Rui; Ren, Jun

2012-01-01

185

Inhibitory effect on proliferation of vascular smooth muscle cells and protective effect on CCl(4)-induced hepatic damage of HEAI extract.  

PubMed

The effects of methanol extract from Hericium erinaceus cultivated with Artemisia iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl(4)-induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs). Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory effect on the proliferation of VSMCs, while a methanol extract of Artemisia iwayomogi possessed strong inhibitory effects on the proliferation of VSMCs. Therefore, the inhibitory effects of HEAI may be caused by the changes of chemical components in the culture broth after the addition of Artemisia iwayomogi in the HEAI growth media. HEAI also had a strong protective effect on CCl(4)-induced hepatic damage in rats. The activity was evaluated using biochemical parameters such as glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP). HEAI treatment caused a significant reduction in the activity of GOT but not of GPT and ALP in comparison with CCl(4) treatment alone. Histopathological studies showed that liver samples treated with HEAI were significantly different when compared to non-treated animals after CCl(4) exposure. PMID:15941638

Choi, Won-Sik; Kim, Chang-Jin; Park, Byeoung-Soo; Lee, Sung-Eun; Takeoka, Gary R; Kim, Dong-Goo; Lanpiao, Xiang; Kim, Jeong-Han

2005-08-22

186

Study on the Mechanism of Oxidative Damage and Genotoxicity induced by BBP in Hepatic cells of Mice  

Microsoft Academic Search

To illustrate the possible function of genotoxicity of BBP on DNA, this study took mice livers as experimental materials to detect the levels of DNA-protein crosslinks (DPC), the activity of surperoxide dismutase (SOD), and the contents of malondialdehyde (MDA) with intraperitioneal injection of different doses of BBP for two consecutive 14 days. DPC levels in hepatic cells showed a dose-dependent

Guo Jing; Wei Chenxi; Hu Chuanlu; Liu Dandan; Yang Xu

2009-01-01

187

Effect of heat stress and recovery on viability, oxidative damage, and heat shock protein expression in hepatic cells of grass carp (Ctenopharyngodon idellus).  

PubMed

In this study, we investigated the effects of hyperthermia and recovery on cell viability, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA), total antioxidant capacity (T-AOC), and heat shock protein (HSP60, 70, and 90) mRNA expression in the hepatic cells of the grass carp, Ctenopharyngodon idellus. Triplicate groups of cultured cells were exposed to 30, 32, or 34 °C for 0.5 h and then immediately incubated at 27 °C in 5 % CO2 for 6, 12, 24, or 48 h. Hyperthermia stress greatly reduced cell viability and increased LDH release. Cell damage declined after recovery. Hyperthermia stress increased the lipid peroxide levels and reduced the antioxidant capacity (e.g., reduced SOD and T-AOC) of the cells. However, oxidative damage declined as the recovery period increased, and the levels of MDA, SOD, and T-AOC were restored. After cells were exposed to 32 °C, the expression of HSP60 after recovery for 1, 2, and 4 h (P < 0.05), the expression of HSP70 after recovery for 0.5 and 1 h (P < 0.01), and the expression of HSP90 throughout recovery were significantly higher (P < 0.01) than the prestress levels. During the recovery period, the variations in HSP gene expression reflected the transition period from a state of cellular growth to one of the cellular repairs. In conclusion, hyperthermia depresses cell viability, induces oxidative damage, and increases HSP expression, which plays an important role during hyperthermic stress in grass carp hepatic cells. PMID:24135954

Cui, Yanting; Liu, Bo; Xie, Jun; Xu, Pao; Habte-Tsion, H-Michael; Zhang, Yuanyuan

2014-06-01

188

ETHANOL-INDUCED DELTA-OPIOID RECEPTOR MODULATION OF GLUTAMATE SYNAPTIC TRANSMISSION AND CONDITIONED PLACE PREFERENCE IN CENTRAL AMYGDALA  

PubMed Central

Alcoholism involves compulsive behaviors of alcohol drinking, which is thought to be related at least initially to the rewarding effect of alcohol. It has been shown that mu-opioid receptors play an essential role in drug reward and dependence for many drugs of abuse including alcohol, but the function of delta-opioid receptors (DOR) in drug reward remains largely unknown at present. Previous animal studies using systemic approaches with DOR antagonists or DOR knockout animals have yielded inconsistent results, showing a decrease, an increase or no change in alcohol consumption and behaviors of alcohol reward after DOR inhibition or deletion. In the present study, we used ethanol-conditioned rats to investigate adaptive DOR function in neurons of the central nucleus of the amygdala (CeA), a key brain site for alcohol reward and addiction. We found that functional DOR was absent in glutamate synapses of CeA neurons from control rats, but it emerged and inhibited glutamate synaptic currents in CeA neurons from rats displaying ethanol-induced behavior of conditioned place preference (CPP). Analysis of paired-pulse ratios and miniature glutamate synaptic currents revealed that the recruited DOR was present on glutamatergic presynaptic terminals. Similar induction of functional DOR was also found on GABA synapses. Furthermore, microinjection of a DOR antagonist into the CeA reversed ethanol-induced CPP behavior in rats in vivo. These results suggest that repeated alcohol exposure recruits new functional DOR on CeA glutamate and GABA synapses, which may be involved in the expression or maintenance of ethanol-induced CPP behavior.

Bie, Bihua; Zhu, Wei; Pan, Zhizhong Z.

2009-01-01

189

Determination of Transaminase Activity in Dogs' Serum and Lymph after Hepatic Damage due to Acute Biliary Obstruction  

Microsoft Academic Search

IT is known that glutamic-oxaloacetic acid transaminase (GOT) and glutamic-pyruvic acid transaminase (GPT) are increased in sera of patients suffering from certain liver diseases1; but there are scarcely any data available about the pathways of these enzymes. We have therefore studied the changes of the concentration of transaminase of hepatic origin at various points of the blood and lymphatic circulation

P. Braun; M. PAPP; I. HORVÁTH

1959-01-01

190

Alpha - Lipoic Acid Decreases DNA Damage and Oxidative Stress Induced by Alcohol in the Developing Hippocampus and Cerebellum of Rat  

Microsoft Academic Search

Background \\/ aims: The present study was initiated in order to investigate the protective effects of ?-lipoic acid upon ethanol-induced DNA damage, lipid peroxidation and protein oxidation in the developing rat hippocampus and cerebellum. Methods: Pregnant Wistar rats received ethanol with, or without lipoic acid from gestation day (GD) 7 throughout lactation. The changes in DNA damage, protein carbonyl, lipid

Alireza Shirpoor; Syranush Minassian; Siamak Salami; Mohammad Hassan Khadem-Ansari; Marine Yeghiazaryan

2008-01-01

191

The DNA Damage Sensors Ataxia-Telangiectasia Mutated Kinase and Checkpoint Kinase 2 Are Required for Hepatitis C Virus RNA Replication?  

PubMed Central

Cellular responses to DNA damage are crucial for maintaining genome integrity, virus infection, and preventing the development of cancer. Hepatitis C virus (HCV) infection and the expression of the HCV nonstructural protein NS3 and core protein have been proposed as factors involved in the induction of double-stranded DNA breaks and enhancement of the mutation frequency of cellular genes. Since DNA damage sensors, such as the ataxia-telangiectasia mutated kinase (ATM), ATM- and Rad3-related kinase (ATR), poly(ADP-ribose) polymerase 1 (PARP-1), and checkpoint kinase 2 (Chk2), play central roles in the response to genotoxic stress, we hypothesized that these sensors might affect HCV replication. To test this hypothesis, we examined the level of HCV RNA in HuH-7-derived cells stably expressing short hairpin RNA targeted to ATM, ATR, PARP-1, or Chk2. Consequently, we found that replication of both genome-length HCV RNA (HCV-O, genotype 1b) and the subgenomic replicon RNA were notably suppressed in ATM- or Chk2-knockdown cells. In addition, the RNA replication of HCV-JFH1 (genotype 2a) and the release of core protein into the culture supernatants were suppressed in these knockdown cells after inoculation of the cell culture-generated HCV. Consistent with these observations, ATM kinase inhibitor could suppress the HCV RNA replication. Furthermore, we observed that HCV NS3-NS4A interacted with ATM and that HCV NS5B interacted with both ATM and Chk2. Taken together, these results suggest that the ATM signaling pathway is critical for HCV RNA replication and may represent a novel target for the clinical treatment of patients with chronic hepatitis C.

Ariumi, Yasuo; Kuroki, Misao; Dansako, Hiromichi; Abe, Ken-Ichi; Ikeda, Masanori; Wakita, Takaji; Kato, Nobuyuki

2008-01-01

192

The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication.  

PubMed

Cellular responses to DNA damage are crucial for maintaining genome integrity, virus infection, and preventing the development of cancer. Hepatitis C virus (HCV) infection and the expression of the HCV nonstructural protein NS3 and core protein have been proposed as factors involved in the induction of double-stranded DNA breaks and enhancement of the mutation frequency of cellular genes. Since DNA damage sensors, such as the ataxia-telangiectasia mutated kinase (ATM), ATM- and Rad3-related kinase (ATR), poly(ADP-ribose) polymerase 1 (PARP-1), and checkpoint kinase 2 (Chk2), play central roles in the response to genotoxic stress, we hypothesized that these sensors might affect HCV replication. To test this hypothesis, we examined the level of HCV RNA in HuH-7-derived cells stably expressing short hairpin RNA targeted to ATM, ATR, PARP-1, or Chk2. Consequently, we found that replication of both genome-length HCV RNA (HCV-O, genotype 1b) and the subgenomic replicon RNA were notably suppressed in ATM- or Chk2-knockdown cells. In addition, the RNA replication of HCV-JFH1 (genotype 2a) and the release of core protein into the culture supernatants were suppressed in these knockdown cells after inoculation of the cell culture-generated HCV. Consistent with these observations, ATM kinase inhibitor could suppress the HCV RNA replication. Furthermore, we observed that HCV NS3-NS4A interacted with ATM and that HCV NS5B interacted with both ATM and Chk2. Taken together, these results suggest that the ATM signaling pathway is critical for HCV RNA replication and may represent a novel target for the clinical treatment of patients with chronic hepatitis C. PMID:18667510

Ariumi, Yasuo; Kuroki, Misao; Dansako, Hiromichi; Abe, Ken-Ichi; Ikeda, Masanori; Wakita, Takaji; Kato, Nobuyuki

2008-10-01

193

Phytochemical, antioxidant and protective effect of Rhus tripartitum root bark extract against ethanol-induced ulcer in rats.  

PubMed

Rhus tripartitum (sumac) is an Anacardiaceae tree with a wide phytotherapeutic application including the use of its roots in the management of gastric ulcer. In the present study the Rhus tripartitum root barks extract (RTE) was phytochemical studied, in vitro tested for their potential antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power assay and in vivo evaluated for its ability to prevent ethanol-induced gastric ulcer in rats. The RTE was rich in phenolics, flavonoids, tannins and polysaccharide contents and exhibited a low but not weak in vitro antioxidant activity when compared with (+)-catechin. Pre-treatment with RTE at oral doses 50, 200 and 400 mg/kg body weight was found to provide a dose-dependent protection against ethanol-induced ulcer by averting the deep ulcer lesions of the gastric epithelium, by reducing gastric juice and acid output, by enhancing gastric mucus production by preserving normal antioxidant enzymes activities, and inhibiting the lipid peroxidation. The antiulcerogenic activity of RTE might be due to a possible synergistic antioxidant and antisecretory effects. PMID:23531841

Alimi, Hichem; Mbarki, Sakhria; Barka, Zeineb B; Feriani, Anwer; Bouoni, Zouhour; Hfaeidh, Najla; Sakly, Mohsen; Tebourbi, Olfa; Rhouma, Khémais B

2013-03-01

194

Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar granule neurons against ethanol-induced apoptotic cell death  

PubMed Central

Alcohol exposure during development can cause brain malformations and neurobehavioral abnormalities. In view of the teratogenicity of ethanol, identification of molecules that could counteract the neurotoxic effects of alcohol deserves high priority. Here, we report that pituitary adenylate cyclase-activating polypeptide (PACAP) can prevent the deleterious effect of ethanol on neuronal precursors. Exposure of cultured cerebellar granule cells to ethanol inhibited neurite outgrowth and provoked apoptotic cell death. Incubation of granule cells with PACAP prevented ethanol-induced apoptosis, and this effect was not mimicked by vasoactive intestinal polypeptide, suggesting that PAC1 receptors are involved in the neurotrophic activity of PACAP. Ethanol exposure induced a strong increase of caspase-2, -3, -6, -8, and -9 activities, DNA fragmentation, and mitochondrial permeability. Cotreatment of granule cells with PACAP provoked a significant inhibition of all of the apoptotic markers investigated although the neurotrophic activity of PACAP could only be ascribed to inhibition of caspase-3 and -6 activities. These data demonstrate that PACAP is a potent protective agent against ethanol-induced neuronal cell death. The fact that PACAP prevented ethanol toxicity even when added 2 h after alcohol exposure, suggests that selective PACAP agonists could have potential therapeutic value for the treatment of fetal alcohol syndrome.

Vaudry, David; Rousselle, Cecile; Basille, Magali; Falluel-Morel, Anthony; Pamantung, Tommy F.; Fontaine, Marc; Fournier, Alain; Vaudry, Hubert; Gonzalez, Bruno J.

2002-01-01

195

Ascorbic acid supplementation enhances recovery from ethanol induced inhibition of Leydig cell steroidogenesis than abstention in male guinea pigs.  

PubMed

The impact of ascorbic acid supplementation against ethanol induced Leydig cell toxicity was studied in guinea pigs. Male guinea pigs were exposed to ethanol (4g/kgb.wt.) for 90 days. After 90 days, ethanol administration was completely stopped and animals in the ethanol group were divided into abstention group and ascorbic acid supplemented group (25mg/100gb.wt.) and those in control group were maintained as control and control+ascorbic acid group. Ethanol administration reduced the serum testosterone and LH (luteinising hormone) levels and elevated estradiol levels. Cholesterol levels in Leydig cell were increased whereas the mRNA and protein expressions of StAR (steroidogenic acute regulatory) protein, cytochrome P450scc (cytochrome p450side chain cleavage enzyme), 3?-HSD (3?-hydroxysteroid dehydrogenase), 17?-HSD (17?-hydroxysteroid dehydrogenase) and LH receptor were drastically reduced. Administration of ascorbic acid resulted in alteration of all these parameters indicating enhanced recovery from ethanol induced inhibition of Leydig cell steroidogenesis. Although abstention could also reduce the inhibition of steroidogenesis, this was lesser in comparison with ascorbic acid supplemented group. PMID:24333212

Radhakrishnakartha, Harikrishnan; Appu, Abhilash Puthuvelvippel; Indira, Madambath

2014-01-15

196

Role of catalase in ethanol-induced conditioned taste aversion: a study with 3-amino-1,2,4-triazole.  

PubMed

Recent studies involved acetaldehyde, the first ethanol metabolite, in both the rewarding and aversive effects of ethanol consumption. Brain acetaldehyde is believed to originate mainly from local brain metabolism of ethanol by the enzyme catalase. Therefore, the inhibition of catalase by 3-amino-1,2,4-triazole (aminotriazole) may help to clarify the involvement of acetaldehyde in ethanol's hedonic effects. In the present study, multiple doses of both ethanol and aminotriazole were used to investigate the effects of catalase inhibition on ethanol-induced conditioned taste aversion (CTA). A separate microdialysis experiment investigated the effects of aminotriazole pretreatment on the time course of brain ethanol concentrations. Ethanol induced a dose-dependent CTA with a maximal effect after conditioning with 2.0 g/kg ethanol. Aminotriazole pretreatments dose-dependently potentiated the CTA induced by 1.0 g/kg ethanol. However, aminotriazole pretreatments did not alter the CTA induced by higher ethanol doses (1.5 and 2.0 g/kg) probably because a maximal aversion for saccharin was already obtained without aminotriazole. The results of the microdialysis experiment confirmed that the effects of aminotriazole cannot be attributed to local alterations of brain ethanol levels. The present study argues against a role for brain acetaldehyde in ethanol's aversive effects but in favor of its involvement in ethanol rewarding properties. PMID:12681527

Quertemont, Etienne; Escarabajal, M Dolores; De Witte, Philippe

2003-05-01

197

Oxidative damage induced by chlorpyrifos in the hepatic and renal tissue of Kunming mice and the antioxidant role of vitamin E.  

PubMed

Chlorpyrifos is a broad-spectrum, chlorinated organophosphate pesticide employed for pest control in various agricultural and animal husbandries. Acute and chronic exposure to CPF can elicit several adverse effects, including oxidative stress. We investigated neurotoxicity of CPF-treated mice, and evaluated the antioxidant effect of vitamin E against oxidative stress and histological changes in the livers and kidneys of CPF-treated mice. Kunming mice were divided randomly into five exposure groups of six: (A) peanut oil; (B) 3mg/kg CPF; (C) 6 mg/kg CPF; (D) 12 mg/kg CPF; (E) vitamin E (100 mg/kg), 3h after administration of CPF (12 mg/kg) and used as a post-treatment group. Oral administration of high-dose groups (12 mg/kg) CPF led to a significant increase in levels of reactive oxygen species, DNA-protein crosslinks, 8-hydroxy-2-deoxyguanosine and malondialdehyde, decreases in acetylcholinesterase activity and glutathione level, as well as causing hepatic and renal histopathological change. Except for AChE activity levels, administration of vitamin E to CPF-treated mice restored these biochemical parameters to within normal levels, and resulted in overall improvement in damage to livers and kidneys. These data suggest that oxidative stress is involved in CPF-induced toxicity and that vitamin E can protect against the tissue damage induced by CPF. PMID:23624379

Ma, Ping; Wu, Yang; Zeng, Qiang; Gan, Yaping; Chen, Jiaoe; Ye, Xin; Yang, Xu

2013-08-01

198

Subchronic effects of smokeless tobacco extract (STE) on hepatic lipid peroxidation, DNA damage and excretion of urinary metabolites in rats  

Microsoft Academic Search

The oral use of moist smokeless tobacco products (snuff) is causally associated with cancer of the mouth, lip, nasal cavities, esophagus and gut. The mechanism by which smokeless tobacco constituents produce genetic and tissue damage is not known. Recent studies in our laboratories have shown that an aqueous extract of smokeless tobacco (STE) activates macrophages with the resultant production of

M Bagchi; D Bagchi; E. A Hassoun; S. J Stohs

1998-01-01

199

Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases  

Microsoft Academic Search

The formation of spatial memory appears to be dependent upon an intact hippocampus capable of the specific biochemical changes associated with synaptic remodeling. Hippocampal damage results in the disruption of synaptic remodeling and the acquisition of spatial memory tasks. Ethanol also disrupts normal hippocampal functioning and spatial memory. The present investigation established a dose–response relationship between ethanol treatment and impairment

John W Wright; Alex J Masino; Jennifer R Reichert; Gary D Turner; Starla E Meighan; Peter C Meighan; Joseph W Harding

2003-01-01

200

Hepatic Protection by Noni Fruit Juice Against CCl 4 Induced Chronic Liver Damage in Female SD Rats  

Microsoft Academic Search

Morinda citrifolia L. (noni) has been used throughout the Pacific, Southeast Asia, Central America, and the Caribbean for a variety of health\\u000a conditions, including heart and liver ailments. In this study, we examined the hepatoprotective effects of TAHITIAN NONI®\\u000a Juice (TNJ) against CCl4-induced chronic liver damage in female Sprague Dawley (SD) rats. Twelve female SD rats were divided into control,

Mian-Ying Wang; Gary Anderson; Diane Nowicki; Jarakae Jensen

2008-01-01

201

Genetic relationship between ethanol-induced conditioned place preference and other ethanol phenotypes in 15 inbred mouse strains.  

PubMed

The genetic relationships between different behaviors used to index the rewarding or reinforcing effects of alcohol are poorly understood. To address this issue, ethanol-induced conditioned place preference (CPP) was tested in a genetically diverse panel of inbred mouse strains, and strain means from this study and other inbred strain studies were used to examine the genetic correlation between CPP and several ethanol-related phenotypes, including activity measures recorded during CPP training and testing. Mice from each strain were exposed to a well-characterized unbiased place conditioning procedure using ethanol doses of 2 or 4 g/kg; an additional group from each strain was exposed to saline alone on all trials. Genotype had a significant effect on CPP, basal locomotor activity, ethanol-stimulated activity, and the effect of repeated ethanol exposure on activity. Correlational analyses showed significant negative genetic correlations between CPP and sweetened ethanol intake and between CPP and test session activity, as well as a significant positive genetic correlation between CPP and chronic ethanol withdrawal severity. Moreover, there was a trend toward a positive genetic correlation between CPP and ethanol-induced conditioned taste aversion. These genetic correlations suggest overlap in the genetic mechanisms underlying CPP and each of these traits. The patterns of genetic relationships suggest a greater impact of ethanol's aversive effects on drinking and a greater impact of ethanol's rewarding effects on CPP. Overall, these data support the idea that genotype influences ethanol's rewarding effect, a factor that may contribute importantly to addictive vulnerability. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:24841742

Cunningham, Christopher L

2014-08-01

202

Effects of the cognition-enhancing agent ABT-239 on fetal ethanol-induced deficits in dentate gyrus synaptic plasticity.  

PubMed

Prenatal ethanol exposure causes deficits in hippocampal synaptic plasticity and learning. At present, there are no clinically effective pharmacotherapeutic interventions for these deficits. In this study, we examined whether the cognition-enhancing agent 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl) benzonitrile (ABT-239), a histamine H(3) receptor antagonist, could ameliorate fetal ethanol-induced long-term potentiation (LTP) deficits. Long-Evans rat dams consumed a mean of 2.82 g/kg ethanol during a 4-h period each day. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, offspring litter size, and birth weights were not different between ethanol-consuming and control groups. A stimulating electrode was implanted in the entorhinal cortical perforant path, and a recording electrode was implanted in the dorsal dentate gyrus of urethane-anesthetized adult male offspring. Baseline input/output responses were not affected either by prenatal ethanol exposure or by 1 mg/kg ABT-239 administered 2 h before data collection. No differences were observed between prenatal treatment groups when a 10-tetanus train protocol was used to elicit LTP. However, LTP elicited by 3 tetanizing trains was markedly impaired by prenatal ethanol exposure compared with control. This fetal ethanol-induced LTP deficit was reversed by ABT-239. In contrast, ABT-239 did not enhance LTP in control offspring using the 3-tetanus train protocol. These results suggest that histamine H(3) receptor antagonists may have utility for treating fetal ethanol-associated synaptic plasticity and learning deficits. Furthermore, the differential effect of ABT-239 in fetal alcohol offspring compared with controls raises questions about the impact of fetal ethanol exposure on histaminergic modulation of excitatory neurotransmission in affected offspring. PMID:20308329

Varaschin, Rafael K; Akers, Katherine G; Rosenberg, Martina J; Hamilton, Derek A; Savage, Daniel D

2010-07-01

203

Adenosine A1 receptors mediate chronic ethanol-induced increases in receptor-stimulated cyclic AMP in cultured hepatocytes.  

PubMed Central

Cellular responses to adenosine depend on the distribution of the two adenosine receptor subclasses. In primary cultures of rat hepatocytes, adenosine receptors were coupled to adenylate cyclase via A1 and A2 receptors which inhibit and stimulate cyclic AMP production respectively. R-(-)-N6-(2-phenylisopropyl)-adenosine (R-PIA), the adenosine A1 receptor-selective agonist, inhibited glucagon-stimulated cyclic AMP production with an IC50 of 19 nM. This inhibition was blocked by the A1-specific antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPDX). 5'-N- Ethylcarboxamidoadenosine (NECA), an agonist which stimulates A2 receptors, increased cyclic AMP production with an EC50 of 0.6 microM. Treatment of primary cultures of rat hepatocytes with 100 mM ethanol for 48 h decreases the quantity and function of the inhibitory guanine-nucleotide regulatory protein (G(i)), resulting in a sensitization of receptor-stimulated cyclic AMP production [Nagy and deSilva (1992) Biochem. J. 286, 681-686]. When cells were cultured with 2 units/ml adenosine deaminase, to degrade extracellular adenosine, ethanol-induced increases in cyclic AMP production were completely prevented. Moreover, the specific A1-receptor antagonist, CPDX, also blocked the chronic effects of ethanol on receptor-stimulated cyclic AMP production. Treatment with adenosine deaminase or CPDX also prevented the decrease in quantity of the alpha subunit protein of G(i) observed in hepatocytes after chronic treatment with ethanol. Taken together, these results suggest that activation of adenosine A1 receptors on primary cultures of hepatocytes is involved in the development of chronic ethanol-induced sensitization of receptor-stimulated cyclic AMP production. Images Figure 3

Nagy, L E; DeSilva, S E

1994-01-01

204

Preventive effect of polysaccharides from the large yellow croaker swim bladder on HCl/ethanol induced gastric injury in mice  

PubMed Central

In the present study the preventive effect of polysaccharides from the large yellow croaker swim bladder (PLYCSB) on HCl/ethanol-induced gastric injury in ICR mice was investigated. A high dose of PLYCSB (50 mg/kg) was found to reduce the levels of the serum proinflammatory cytokines interleukin (IL)-1?, IL-6, IL-8, as well as increase the levels of IL-4 compared with those in mice treated with a low dose of PLYCSB (25 mg/kg) and control mice. The somatostatin and vasoactive intestinal peptide serum levels in PLYCSB-treated mice were higher compared with those in control mice, whilst motilin and substance P serum levels were lower compared with those in control mice. The extent of the gastric injury in the mice treated with PLYCSB was lower compared with that in the control mice; however, the results obtained for mice treated with a high dose of PLYCSB were similar to those for omeprazole-treated mice. In addition, the superoxide dismutase and glutathione peroxidase activities of PLYCSB-treated mice were higher compared with those of the control mice, and similar to those observed in normal and omeprazole-treated mice. Furthermore, PLYCSB-treated mice showed levels of nitric oxide and malondialdehyde that were similar to those in the normal group. Using PCR and western blot analysis, it was demonstrated that PLYCSB significantly inhibited inflammation in the tissues of the HCl/ethanol induced gastric injury mice by downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-? and IL-1?. These results suggest that PLYCSB has an inhibitory effect against gastric injury that is comparable to that of the gastric injury drug omeprazole. Therefore, PLYCSB has the potential to be used as a natural therapeutic drug.

CHEN, SHAOCHENG; ZHU, KAI; WANG, RUI; ZHAO, XIN

2014-01-01

205

Cilnidipine, an L/N-type calcium channel blocker prevents acquisition and expression of ethanol-induced locomotor sensitization in mice.  

PubMed

Several evidences indicated the involvement of L- and N-type calcium channels in behavioral effects of drugs of abuse, including ethanol. Calcium channels are implicated in ethanol-induced behaviors and neurochemical responses. Calcium channel antagonists block the psychostimulants induced behavioral sensitization. Recently, it is demonstrated that L-, N- and T-type calcium channel blockers attenuate the acute locomotor stimulant effects of ethanol. However, no evidence indicated the role of calcium channels in ethanol-induced psychomotor sensitization. Therefore, present study evaluated the influence of cilnidipine, an L/N-type calcium channel blocker on acquisition and expression of ethanol-induced locomotor sensitization. The results revealed that cilnidipine (0.1 and 1.0?g/mouse, i.c.v.) attenuates the expression of sensitization to locomotor stimulant effect of ethanol (2.0g/kg, i.p.), whereas pre- treatment of cilnidipine (0.1 and 1.0?g/mouse, i.c.v.) during development of sensitization blocks acquisition and attenuates expression of sensitization to locomotor stimulant effect of ethanol. Cilnidipine per se did not influence locomotor activity in tested doses. Further, cilnidipine had no influence on effect of ethanol on rotarod performance. These results support the hypothesis that neuroadaptive changes in calcium channels participate in the acquisition and the expression of ethanol-induced locomotor sensitization. PMID:22402189

Bhutada, Pravinkumar; Mundhada, Yogita; Patil, Jayshree; Rahigude, Anand; Zambare, Krushna; Deshmukh, Prashant; Tanwar, Dhanshree; Jain, Kishor

2012-04-11

206

A Systems-Based Computational Model for Dose-Response Comparisons of Two Mode of Action Hypotheses for Ethanol-Induced Neurodevelopmental Toxicity  

Microsoft Academic Search

Investigations into the potential mechanisms for ethanol- induced developmental toxicity have been ongoing for over 30 years since Fetal Alcohol Syndrome (FAS) was first described. Neurodevelopmental endpoints are particularly sensitive to in utero exposure to alcohol as suggested by the more prevalent alcohol-related neurodevelopmental disorder (ARND). The in- hibition of proliferation during neurogenesis and the induction of apoptosis during the

J. M. Gohlke; W. C. Griffith; E. M. Faustman

2005-01-01

207

Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors  

Microsoft Academic Search

BACKGROUND: The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem

Daniel R Santillano; Leena S Kumar; Terasa L Prock; Cynthia Camarillo; Joseph D Tingling; Rajesh C Miranda

2005-01-01

208

An Early Complement-Dependent and TLR-4Independent Phase in the Pathogenesis of Ethanol-Induced Liver Injury in Mice  

Microsoft Academic Search

The innate immune system has been implicated in the pathogenesis of alcoholic liver disease. Although innate immunity is usually considered an early response to injury, previous work implicating innate immunity in ethanol-induced liver injury focuses primarily on long-term ethanol exposure. We investigated the early period of ethanol exposure to determine whether there were temporal associations between activation of innate immune

Sanjoy Roychowdhury; Megan R. McMullen; Michele T. Pritchard; Amy G. Hise; Nico van Rooijen; M. Edward Medof; Abram B. Stavitsky; Laura E. Nagy

2009-01-01

209

AMELIORATION OF ETHANOL-INDUCED DYSMORPHOGENESIS BY ADENOVIRAL-MEDIATED CU,ZN-SOD AND MN-SOD EXPRESSION IN NEURULATION STAGED MOUSE EMBRYOS IN VITRO  

EPA Science Inventory

AMELIORATION OF ETHANOL-INDUCED DYSMORPHOGENESIS BY ADENOVIRAL-MEDIATED Cu,Zn-SOD AND Mn-SOD EXPRESSION IN NEURULATION STAGED MOUSE EMBRYOS IN VITRO. JB Smith1, PC Hartig3, MR Blanton3, KK Sulik1,2, and ES Hunter3. 1Department of Cell and Developmental Biology and 2Bowles Cente...

210

Protective effects of lysophosphatidic acid (LPA) on chronic ethanol-induced injuries to the cytoskeleton and on glucose uptake in rat astrocytes  

Microsoft Academic Search

Ethanol induces severe alterations in membrane trafficking in hepatocytes and astrocytes, the molecular basis of which is unclear. One of the main candidates is the cytoskeleton and the molecular components that regulate its organization and dynamics. Here, we examine the effect of chronic exposure to ethanol on the organization and dynamics of actin and micro- tubule cytoskeletons and glucose uptake

Monica Tomas; Francisco Lazaro-Dieguez; Juan M. Duran; Pilar Marin; Jaime Renau-Piqueras; Gustavo Egea

2003-01-01

211

Hepatoprotective Activity of Methanolic Extract of Bauhinia purpurea Leaves against Paracetamol-Induced Hepatic Damage in Rats  

PubMed Central

In an attempt to further establish the pharmacological properties of Bauhinia purpurea (Fabaceae), hepatoprotective potential of methanol extract of B. purpurea leaves (MEBP) was investigated using the paracetamol- (PCM-) induced liver toxicity in rats. Five groups of rats (n = 6) were used and administered orally once daily with 10% DMSO (negative control), 200?mg/kg silymarin (positive control), or MEBP (50, 250, and 500?mg/kg) for 7 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay with the total phenolic content (TPC) also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of the normal hepatic structural was observed in group pretreated with silymarin and MEBP. Hepatotoxic rats pretreated with silymarin or MEBP exhibited significant decrease (P < 0.05) in ALT and AST enzyme level. Moreover, the extract also exhibited antioxidant activity and contained high TPC. In conclusion, MEBP exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and high phenolic content and thus warrants further investigation.

Yahya, F.; Mamat, S. S.; Kamarolzaman, M. F. F.; Seyedan, A. A.; Jakius, K. F.; Mahmood, N. D.; Shahril, M. S.; Suhaili, Z.; Mohtarrudin, N.; Susanti, D.; Somchit, M. N.; Teh, L. K.; Salleh, M. Z.; Zakaria, Z. A.

2013-01-01

212

Short-chain fatty acids activate AMP-activated protein kinase and ameliorate ethanol-induced intestinal barrier dysfunction in Caco-2 cell monolayers.  

PubMed

Short-chain fatty acids (SCFAs) have been shown to promote intestinal barrier function, but their protective effects against ethanol-induced intestinal injury and underlying mechanisms remain essentially unknown. The aim of the study was to analyze the influence of SCFAs on ethanol-induced barrier dysfunction and to examine the role of AMP-activated protein kinase (AMPK) as a possible mechanism using Caco-2 monolayers. The monolayers were treated apically with butyrate (2, 10, or 20 mmol/L), propionate (4, 20, or 40 mmol/L), or acetate (8, 40, or 80 mmol/L) for 1 h before ethanol (40 mmol/L) for 3 h. Barrier function was analyzed by measurement of transepithelial resistance and permeation of fluorescein isothiocyanate-labeled dextran. Distribution of the tight junction (TJ) proteins zona occludens-1, occludin, and filamentous-actin (F-actin) was examined by immunofluorescence. Metabolic stress was determined by measuring oxidative stress, mitochondrial function, and ATP using dichlorofluorescein diacetate, dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, and bioluminescence assay, respectively. AMPK was knocked down by small interfering RNA (siRNA), and its activity was assessed by a cell-based ELISA. Exposure to ethanol significantly impaired barrier function compared with controls (P < 0.0001), disrupted TJ and F-actin cytoskeleton integrity, and induced metabolic stress. However, pretreatment with 2 mmol/L butyrate, 4 mmol/L propionate, and 8 mmol/L acetate significantly alleviated the ethanol-induced barrier dysfunction, TJ and F-actin disruption, and metabolic stress compared with ethanol-exposed monolayers (P < 0.0001). The promoting effects on barrier function were abolished by inhibiting AMPK using either compound C or siRNA. These observations indicate that SCFAs exhibit protective effects against ethanol-induced barrier disruption via AMPK activation, suggesting a potential for SCFAs as prophylactic and/or therapeutic factors against ethanol-induced gut leakiness. PMID:24132573

Elamin, Elhaseen E; Masclee, Ad A; Dekker, Jan; Pieters, Harm-Jan; Jonkers, Daisy M

2013-12-01

213

Association of Iron Overload with Oxidative Stress, Hepatic Damage and Dyslipidemia in Transfusion-Dependent ?-Thalassemia/HbE Patients.  

PubMed

Blood transfusion can be a life-saving therapy for ?-thalassemia major and ?-thalassemia/HbE (?-TM) patients with chronic anemia, major caused severe iron overload particularly in ?-TM patients received only blood transfusion therapy. We aim to evaluate the association of iron overload with oxidative stress, liver damage, and elevated very low density lipoprotein cholesterol (VLDL-C) in transfusion-dependent ?-TM patients. Serum ferritin, malondialdehyde (MDA), liver profiles, triglycerides levels, and VLDL-C were significantly higher while total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and total antioxidant capacity were lower in ?-TM than controls. Serum ferritin was significantly correlated with MDA, liver enzymes and lipid profiles (p < 0.05). Multiple forward stepwise linear regression analyses of the significant variables showed that in these ?-TM patients, independent predictors of iron overload were MDA (? = 0.410, r (2) = 0.671, p < 0.001), ALT (? = 0.493, r (2) = 0.578, p < 0.001), and VLDL-C (? = 0.253, r (2) = 0.711, p < 0.001). In conclusion, iron overload associated with increased oxidative stress, lipid peroxidation, liver damage, decreased TC, LDL-C, HDL-C and over production of VLDL-C, is significantly problem in transfusion-dependent ?-TM patients. These appeared the major cause of future morbidity and mortality in ?-TM patients. PMID:24966477

Sengsuk, Chintana; Tangvarasittichai, Orathai; Chantanaskulwong, Prasert; Pimanprom, Ampai; Wantaneeyawong, Somsak; Choowet, Anuchit; Tangvarasittichai, Surapon

2014-07-01

214

Effect of anthocyanin-rich extract from black rice (Oryza sativa L. Japonica) on chronically alcohol-induced liver damage in rats.  

PubMed

The study evaluated the protective effect of anthocyanin-rich extract from black rice (AEBR) on chronic ethanol-induced biochemical changes in male Wistar rats. Administration of ethanol (3.7 g/kg/day) to Wistar rats for 45 days induced liver damage with a significant increase (P < 0.05) of aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) in the serum and the hepatic malondialdehyde (MDA) level. In contrast, administration of AEBR (500 mg/kg) along with alcohol significantly (P < 0.01) decreased the activities of liver enzymes (AST, ALT and GGT) in serum, the MDA levels and the concentrations of serum and hepatic triglyceride (TG) and total cholesterol (TCH). Rats treated with AEBR showed a better profile of the antioxidant system with normal glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione S-transferase (GST) activities. All these results were accompanied by histological observations in liver. The results demonstrate that AEBR has a beneficial effect in reducing the adverse effect of alcohol. PMID:20143824

Hou, Zhaohua; Qin, Peiyou; Ren, Guixing

2010-03-10

215

Hepatic ischemia induced immediate oxidative stress after reperfusion and determined the severity of the reperfusion-induced damage.  

PubMed

Noninvasive evaluation of organ redox states provides invaluable information in many clinical settings. We evaluated a newly developed reduction/oxidation-sensitive green fluorescent protein (roGFP) probe that reports cellular redox potentials and their dynamic changes in live cells. On hypoxia/reoxygenation (H/R) of AML12 liver cells, roGFP indicated mild reduction during hypoxia, but immediate transient oxidation after reoxygenation. The roGFP probe confirmed the antioxidative effects of N-acetylcysteine, catalase, redox factor-1, and Mn-SOD/CuZn-SOD against H/R-induced cellular oxidative stress (OS). In a mouse liver ischemia/reperfusion (I/R) model, roGFP transduced by using an adenoviral vector revealed immediate reduction of the liver under ischemia, and two distinct peaks of OS: (a) early, observed within 60 min after reperfusion, similar to the in vitro study; and (b) later, at 24 h. The early peak levels paralleled the ischemic time up to 75 min and the postischemic liver injury (sGOT/GPT/LDH) in the later phase (6 and 24 h after I/R). The roGFP probe successfully indicated postischemic OS of the liver in living mice, accurately predicting postischemic liver injury. This probe may represent an effective OS marker indicating organ redox states and also predicting the damage/function. PMID:19489709

Haga, Sanae; Remington, S James; Morita, Naoki; Terui, Keita; Ozaki, Michitaka

2009-10-01

216

Phytochemical analysis and hepatoprotective properties of Tinospora cordifolia against carbon tetrachloride-induced hepatic damage in rats.  

PubMed

The present study was conducted to evaluate the hepatoprotective activity of different extracts of Tinospora cordifolia against carbon tetrachloride (CCl4) induced liver damage in rats. The pet ether, ethanol and aqueous extracts of various parts of the plant such as leaf, stem and root were tested at the dose of 200mg/kg body weight orally using Wistar albino rats and Silymarin was given as reference standard. Ethanolic extract of all the parts showed significant hepatoprotective effect by reduction in serum enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBL) in the selected model which is followed by aqueous and pet ether extracts. The chemical constituents reported from the plant belong to different classes such as alkaloids, flavanoids, glycosides, steroids, terpenoids, phenolics and saponins. The overall experimental results suggests that the biologically active phytoconstituents such as flavonoids, alkaloids present in the ethanolic extract of plant Tinospora cordifolia, may be responsible for the significant hepatoprotective activity. Therefore, results justify the use of Tinospora cordifolia as a hepatoprotective agent. PMID:24826014

Kavitha, B T; Shruthi, S D; Rai, S Padmalatha; Ramachandra, Y L

2011-06-01

217

Phytochemical analysis and hepatoprotective properties of Tinospora cordifolia against carbon tetrachloride-induced hepatic damage in rats  

PubMed Central

The present study was conducted to evaluate the hepatoprotective activity of different extracts of Tinospora cordifolia against carbon tetrachloride (CCl4) induced liver damage in rats. The pet ether, ethanol and aqueous extracts of various parts of the plant such as leaf, stem and root were tested at the dose of 200mg/kg body weight orally using Wistar albino rats and Silymarin was given as reference standard. Ethanolic extract of all the parts showed significant hepatoprotective effect by reduction in serum enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBL) in the selected model which is followed by aqueous and pet ether extracts. The chemical constituents reported from the plant belong to different classes such as alkaloids, flavanoids, glycosides, steroids, terpenoids, phenolics and saponins. The overall experimental results suggests that the biologically active phytoconstituents such as flavonoids, alkaloids present in the ethanolic extract of plant Tinospora cordifolia, may be responsible for the significant hepatoprotective activity. Therefore, results justify the use of Tinospora cordifolia as a hepatoprotective agent

Kavitha, B. T.; Shruthi, S. D.; Rai, S. Padmalatha; Ramachandra, Y. L.

2011-01-01

218

Potentiation of ethanol-induced pancreatic injury by dietary fat. Induction of chronic pancreatitis by alcohol in rats.  

PubMed Central

Effects of sustained ethanol intoxication and dietary fat content on pancreatic morphology were investigated in the rat model implanted with gastrostomy catheters, which permitted continuous intragastric infusion of ethanol plus liquid diet containing one of three levels of corn oil: 5% (low-fat), 25% (high-fat), and 35% (extra-high-fat) of total calories. After various durations of infusion ranging from 30 to 160 days, the pancreatic histology was examined. Mean blood alcohol levels achieved in the low, high, and extra-high fat diet groups were similarly high: 210 +/- 120, 224 +/- 122, and 289 +/- 110 mg/dl. The average weight gain of these ethanol-fed groups during the first 8 weeks of experiments was 15.4 +/- 1.9, 19.6 +/- 8.0, and 14.9 +/- 5.2 g/wk, respectively, and was not statistically different from that of pair-fed controls infused with isocaloric amount of dextrose and respective diet, nor from that of age-matched animals given the regular chow. None of control animals showed abnormal pancreatic morphologic features except occasional mild steatosis in those fed the extra-high-fat diet. With the low dietary intake of unsaturated fat, chronic ethanol intoxication produced only mild pancreatic pathology such as steatosis and interstitial edema. Administration of ethanol and the high-fat and extra-high-fat diets caused hypogranulation and apoptosis of acinar cells. Focal lesions of chronic pancreatitis were also observed in 20% or 30% of ethanol-fed animals given the high-fat or extra-high-fat diet. These lesions were characterized by fat necrosis, mononuclear cell infiltration, fibrosis, acinar atrophy, ductal dilatation, and intraductal mucious or proteinacious plugs. The incidence of focal acute pancreatitis was less (7-20%) but appeared increased with higher dietary fat content. Induction of either acute or chronic pancreatitis was not correlated with plasma levels of triglycerides or cholesterol. These results demonstrate potentiation by dietary unsaturated fat of ethanol-induced pancreatic injury. This model possesses many features analogous to those seen in alcoholic pancreatic injury in man. The hyperlipidemia does not appear to be an important pathogenetic factor for ethanol-induced pancreatitis produced in this model. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9

Tsukamoto, H.; Towner, S. J.; Yu, G. S.; French, S. W.

1988-01-01

219

Lipid peroxidation and hepatic antioxidants in alcoholic liver disease.  

PubMed Central

The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation.

Situnayake, R D; Crump, B J; Thurnham, D I; Davies, J A; Gearty, J; Davis, M

1990-01-01

220

Dillapiole, isolated from Peperomia pellucida, shows gastroprotector activity against ethanol-induced gastric lesions in Wistar rats.  

PubMed

Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of P. pellucida using an ethanol-induced gastric ulcer experimental rat model. A gastroprotective effect was observed when the hexane and dichloromethane extracts were tested, with the higher effect being obtained with the dichloromethane extract (82.3 ± 5.6%) at 100 mg/kg. Dillapiole was identified as the most active compound in this extract. Although there have been previous reports on dillapiole, this is the first on its gastroprotective activity. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 23.1, 56.1, 73.2 and 85.5% gastroprotection, respectively. The effect elicited by dillapiole at 100 mg/kg was not attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), a prostaglandin synthesis blocker, NG-nitro-l-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of dillapiole does not involve prostaglandins, NO or sulfhydryl groups. PMID:24064453

Rojas-Martínez, Raúl; Arrieta, Jesús; Cruz-Antonio, Leticia; Arrieta-Baez, Daniel; Velázquez-Méndez, Antonio Magdiel; Sánchez-Mendoza, María Elena

2013-01-01

221

Effects of CA antagonists on ethanol-induced excitation in habituated and nonhabituated mice: interaction with stress factors?  

PubMed

The effects of CA antagonists on ethanol induced locomotion in habituated (N) and nonhabituated (NH) mice was examined. H-mice were exposed to the testing apparatus for 4 days before testing. Mice were pretreated with pimozide (D2 antagonist), Schering 23390 (D1 antagonist), phenoxybenzamine (alpha 1 antagonist), or yohimbine (alpha 2 antagonist). Mice were then treated with ethanol. H mice had lower activity scores compared to NH mice. Ethanol produced an increase in activity for both groups. In NH animals, pimozide attenuated excitation in inverse relation to the ethanol dosage. In H mice, pimozide attenuated excitation only at doses that in themselves produced a decrease in activity. Schering 23390 reduced excitation only at doses that affected activity per se in both groups. Phenoxybenzamine reduced excitation dose-dependently in both groups. Yohimbine decreased excitation in both groups. Results suggest that stress emanating from a novel environment may affect not only activity per se but also the interaction between CA antagonists and ethanol. PMID:8385782

Koechling, U M; Amit, Z

1993-04-01

222

The effect of calorie restriction on acute ethanol-induced oxidative and nitrosative liver injury in rats.  

PubMed

The aim of our study was to examine the effect of calorie restriction (CR) on oxidative and nitrosative liver injury in rats, induced by acute ethanol intoxication. Male Wistar rats were divided into groups: (1) control; (2) calorie-restricted groups with intake of 60-70% (CR60-70) and 40-50% of daily energy needs (CR40-50); (3) ethanol-treated group (E); (4) calorie-restricted, ethanol-treated groups (E+CR60-70 and E+CR40-50). Ethanol was administered in 5 doses of 2g/kg every 12h, and duration of CR was 5 weeks before ethanol treatment. Malondialdehyde and nitrite and nitrate level were significantly lower in E+CR60-70 and higher in E+CR40-50 vs. E group. Liver reduced glutathione content and activity of both superoxide dismutase izoenzymes were significantly higher in E+CR60-70 and lower in E+CR40-50 vs. E group. Oxidative stress may be a potential mechanism of hormetic effects of CR on acute ethanol-induced liver injury. PMID:23686010

Mladenovi?, Dušan; Ninkovi?, Milica; Aleksi?, Vuk; Šljivan?anin, Tamara; Vu?evi?, Danijela; Todorovi?, Vera; Stankovi?, Milena; Stanojlovi?, Olivera; Radosavljevi?, Tatjana

2013-09-01

223

Effects of somatostatin and some of its tetrapeptide fragments on ethanol - induced gastric mucosal erosion in rat  

SciTech Connect

A study was made of the cytoprotective effects of somatostatin (SRIF) and its 3-6, 5-8, 7-10, 9-12 and 11-14 tetrapeptide fragments on absolute ethanol-induced hemorrhagic erosions in the stomach of rat. The SRIF molecule was found to prevent the gastric erosions induced by ethanol. The 7-10 and 11-14 fragments exhibited similar properties. There are two peaks in the cytoprotective dose-response curves. It is concluded that various fragments of SRIF can also exert cytoprotective effects. SRIF is superior to cimetidine in the therapy of bleeding duodenal and gastric ulcers in humans. It prevents the duodenal ulcer produced by cysteamine and the gastric ulcer caused by stress. According to Szabo and Usadel, SRIF has a cytoprotective property, i.e. it decreases the harmful effects of absolute ethanol on the stomach of rat. The aim of this study was to establish whether various SRIF fragment have protective effects, and how the cytoprotection depends on the doses applied. 18 references, 1 figure.

Laszlo, F.; Pavo, I.; Penke, B.; Balint, G.A.

1987-08-31

224

Cinitapride protects against ethanol-induced gastric mucosal injury in rats: role of 5-hydroxytryptamine, prostaglandins and sulfhydryl compounds.  

PubMed

This study was designed to determine the gastroprotective properties of cinitapride (CNT), a novel prokinetic benzamide derivative agonist of 5-HT4 and 5-HT1 receptors and 5-HT2 antagonist, on mucosal injury produced by 50% (v/v) ethanol. Results were compared with those for 5-hydroxytryptamine (5-HT: 10 mg kg-1). The possible involvements of gastric mucus secretion, endogenous prostaglandins (PGs) and sulfhydryl compounds (SH) in the protection mediated by CNT were also examined. Intraperitoneal administration of CNT (0.50 and 1 mg kg-1), 30 min before ethanol, significantly prevented gastric ulceration and increased the hexosamine content of gastric mucus. CNT (1 mg kg-1) also produced a significant increase in gastric mucosal levels of PGE2, but did not induce any significant changes in SH values. On the contrary, pretreatment with 5-HT worsened ethanol-induced erosions, however, did not affect gastric mucus secretion, glycoprotein content or PGE2 levels, although the non-protein SH fraction was significantly decreased. The present results demonstrate that the gastroprotective effects of CNT could be partly explained by a complex PG dependent mechanism. We suggest that 5-HT dependent mechanisms through 5-HT2 receptor blockade and 5-HT1 receptor activation could be also involved. PMID:9211565

Alarcón-de-la-Lastra Romero, C; López, A; Martín, M J; la Casa, C; Motilva, V

1997-04-01

225

Prevention of ethanol-induced vascular injury and gastric mucosal lesions by sucralfate and its components: possible role of endogenous sulfhydryls  

SciTech Connect

The authors tested the hypothesis that sucralfate, which contains eight sulfate and aluminum molecules on a sucrose and its other components might decrease ethanol-induced vascular injury and hemorrhagic mucosal lesions through a sulfhydryl (SH)-sensitive process. Experiments performed in rats revealed that the entire sucralfate molecule is not a prerequisite for protection against ethanol-induced mucosal vascular injury and erosions. It appears that sulfate and sucrose octasulfate are potent components of sucralfate, although an equimolar amount of sucralfate is at least twice as effective in gastroprotection than its components. The SH alkylator N-ethylmaleimide abolished the gastroprotection by sucralfate, suggesting SH-sensitive process in the mucosal protection which seems to be associated with the prevention of rapidly developing vascular injury in the stomach of rats given ethanol.

Szabo, S.; Brown, A.

1987-09-01

226

Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity.  

PubMed

The role of steatosis in the progression of liver damage in chronic hepatitis C (CHC) was studied. Enrolled were 180 consecutive liver biopsy-proven CHC patients and 41 additional subjects with a known duration of infection. We evaluated the histological activity index (HAI), grade of fibrosis and steatosis, body mass index (BMI; kg/m(2)), distribution of body fat, HCV genotype, and levels of HCV RNA. Eighty six (48%) patients showed steatosis, and a higher prevalence was observed in genotype 3a infection (P <.01). A correlation between the grade of steatosis and fibrosis was observed (P <.001). Fibrosis was also associated with age (P <.001). After adjusting for age, the association between steatosis and fibrosis remained significant. The grade of steatosis also correlated with the HAI (P <.007) with a significant increase in periportal necrosis. No relation was found between steatosis and age, gender, iron storage, or levels of HCV RNA. Patients with a high grade of steatosis (>30%) showed higher serum levels of gamma-GT and ALT (P <.001). Overall, steatosis was not significantly associated to BMI. Analysis by single genotype showed a significant association between the grade of steatosis and BMI in type 1 infection r =.689; P <.001) and with levels of HCV RNA in type 3a infection r =.786; P <.001). Visceral fat distribution rather than BMI proved to be associated with steatosis (P <.001). Data obtained from patients with a known date of infection confirmed that steatosis grades 3-4 were associated with a higher annual rate of fibrosis progression, and showed that alcohol and steatosis act together in increasing fibrosis (P <.05). Our data indicate that steatosis is an important cofactor in increasing liver necroinflammatory activity and in accelerating fibrosis in CHC. Visceral obesity and genotype 3a play a role in the development of steatosis. PMID:11391523

Adinolfi, L E; Gambardella, M; Andreana, A; Tripodi, M F; Utili, R; Ruggiero, G

2001-06-01

227

Modulation of Atg5 expression by globular adiponectin contributes to autophagy flux and suppression of ethanol-induced cell death in liver cells.  

PubMed

Globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis via induction of autophagy. However, the underlying mechanisms are unknown. The present study aims to investigate the potential role of autophagy-related protein 5 (Atg5), an essential Atg for the elongation of autophagosomes, in suppression of ethanol-induced cytotoxicity by gAcrp. Here, we demonstrated that suppression of Atg5 expression by ethanol was restored by pretreatment with gAcrp both in primary rat hepatocytes and human hepatoma cell line (HepG2). Moreover, ethanol-induced accumulation of p62 (sequestosome1), a marker of autophagic flux, was restored by gAcrp treatment, implying that gAcrp modulates autophagic flux in liver cells. Further, Atg5 silencing prevented p62 degradation by gAcrp, suggesting that Atg5 plays a critical role in induction of autophagic flux by gAcrp. Interestingly, gene silencing of Atg5 by siRNA abrogated restoration of autophagosome formation by gAcrp in ethanol-treated cells. Finally, protection of liver cells by gAcrp from ethanol-induced apoptosis was also significantly attenuated by knocking-down of Atg5 expression, suggesting an important role of Atg5 in autophagy induction and cellular apoptosis modulated by gAcrp. Taken together, our data demonstrated that Atg5 expression, at least in part, is implicated in gAcrp-induced autophagy and subsequent anti-apoptotic effects in ethanol-treated liver cells. PMID:24582693

Nepal, Saroj; Kim, Mi Jin; Lee, Eung-Seok; Kim, Jung-Ae; Choi, Dong-Young; Sohn, Dong-Hwan; Lee, Sung-Hee; Song, Kyung; Kim, Sang-Hyun; Jeong, Gil-Saeng; Jeong, Tae Cheon; Park, Pil-Hoon

2014-06-01

228

KNOCKDOWN OF GCN5 HISTONE ACETYLTRANSFERASE by siRNA DECREASES ETHANOL INDUCED HISTONE ACETYLATION AND AFFECTS DIFFERENTIAL EXPRESSION OF GENES IN HUMAN HEPATOMA CELLS  

PubMed Central

We have investigated whether Gcn5, a histone acetyltransferase (HAT), is involved in ethanol induced acetylation of histone H3 at lysine 9 (H3AcK9) and has any effect on the gene expression. Human hepatoma HepG2 cells transfected with ethanol metabolizing enzyme alcohol dehydrogenase 1 (VA 13 cells) were used. Knockdown of Gcn5 by siRNA silencing decreased mRNA and protein levels of GCN5, HAT activity, and also attenuated ethanol induced H3AcK9 in VA13 cells. Illumina gene microarray analysis using total RNA showed 940 transcripts affected by GCN5 silencing or ethanol. Silencing caused differential expression of 891 transcripts (? 1.5 fold up- or down- regulated). Among these, 492 transcripts were up- and 399 were down- regulated compared to their respective controls. Using a more stringent threshold (? 2.5 fold) the array data from GCN5 silenced samples showed 57 genes differentially expressed (39 up-regulated and 18 down-regulated). Likewise, ethanol caused differential regulation of 57 transcripts with ? 1.5 fold change (35 gene up-regulated and 22 down-regulated). Further analysis showed that eight genes were differentially regulated that were common for both ethanol treatment and GCN5 silencing. Among these, SLC44A2 (a putative choline transporter) was strikingly up-regulated by ethanol (3 fold), and GCN5 silencing down regulated it (1.5 fold). The quantitative RT-PCR profile corroborated the array findings. This report demonstrates for the first time that (a) GCN5 differentially affects expression of multiple genes, (b) ethanol induced histone H3-lysine 9 acetylation is mediated via GCN5 and (c) that GCN5 is involved in ethanol induced expression of the putative choline transporter SLC44A2.

Choudhury, Mahua; Pandey, Ravi S.; Clemens, Dahn L.; Davis, J. Wade; Lim, Robert W.; Shukla, Shivendra D.

2011-01-01

229

Effects of electroacupuncture on ethanol-induced impairments of spatial learning and memory and Fos expression in the hippocampus in rats.  

PubMed

It is well established that alcohol impairs spatial learning and memory. Here, we investigated the effects of electroacupuncture (EA) at ST36 or nonacupoint on ethanol-induced learning and memory impairment and the expression of Fos in the hippocampus. Ethanol (5g/kg) was administered intragastrically once a day for 5 consecutive days; 2Hz EA was administered immediately after ethanol exposure. After a 2-day ethanol abstinence, for 6 consecutive days, the rats were submitted to Morris water maze training. Probe trials were performed on 1 day after the final training session. We also applied immunohistochemistry to detect Fos-positive nuclei in the hippocampus. We found that 5-day ethanol exposure markedly decreased spatial learning and memory abilities in the Morris water maze task as indicated by escape latency and time in the target quadrant. EA treatment shortened the time of reaching platform and increased times traveled in the target quadrant (P<0.05). Animals administered with ethanol emitted significantly fewer Fos expression in the hippocampal CA1 area. EA increased Fos expression in the hippocampal CA1 area. Significant correlations were obtained between Fos protein expression in CA1 and time in the target quadrant. Altogether, these results suggest that EA protects against ethanol-induced impairments of spatial learning and memory, which may be involved in the hippocampal CA1 area. EA treatment may provide a novel nonpharmacological strategy for ethanol-induced learning and memory impairment. PMID:24923763

Lu, Bin; Ma, Zhao; Cheng, Fei; Zhao, Yan; Zhang, Xin; Mao, Huijuan; Shen, Xueyong; Liu, Sheng

2014-07-25

230

Acute toxicity and gastroprotective effect of the Schiff base ligand ąH-indole-3-ethylene-5-nitrosalicylaldimine and its nickel (II) complex on ethanol induced gastric lesions in rats.  

PubMed

The present study was performed to evaluate the gastroprotective activity of Schiff base ligand derived from the condensation reaction of tryptamine (an indole derivative) and 5-nitrosalicylaldehyde (TNS) and its nickel (II) complex against ethanol-induced gastric ulcer in rats. The compounds were orally administered with low (30 mg/kg) and high (60 mg/kg) doses to ulcer-induced Sprague-Dawley rats. Macroscopically, the ulcer control group exhibited severe mucosal injury, whereas pre-treatment with either cimetidine or TNS and its nickel (II) complex each resulted in significant protection against gastric mucosal injury. Flattening of gastric mucosal folds was also observed in rats pretreated with TNS and its nickel complex. Histological studies of the gastric wall of ulcer control group revealed severe damage of gastric mucosa, along with edema and leucocytes infiltration of the submucosal layer compared to rats pre-treated with either cimetidine or TNS and its nickel (II) compound, where there was marked gastric protection along with reduction of edema and leucocytes infiltration of the submucosal layer. Acute toxicity study done on mice with a higher dose of 5 g/kg of TNS and its nickel (II) complex did not manifest any toxicological signs. Research finding suggest that TNS and its nickel (II) complex could be considered as effective gastroprotective compounds. PMID:23090023

Ibrahim, Mohamed Mustafa; Ali, Hapipah Mohd; Abdullah, Mahmood Ameen; Hassandarvish, Pouya

2012-01-01

231

Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats.  

PubMed

Previous studies have shown that treatment with ghrelin exhibits protective and therapeutic effects in the gut. Aim of our present investigation was to examine the influence of ghrelin administration on the healing of ethanol-induced gastric ulcers and determine the role of cyclooxygenase-1 and cyclooxygenase-2 in this effect. Our studies were performed on male Wistar rats. Gastric ulcers were induced by intragastric administration of 75% ethanol. Ghrelin alone or in combination with cyclooxygenase inhibitors was administered twice, 1 and 13 hours after ethanol application. Cyclooxygenase-1 (COX-1) inhibitor (SC-560, 10 mg/kg/dose) or COX-2 inhibitor (celecoxib, 10 mg/kg/dose) were given 30 min prior to ghrelin. Twelve or 24 hours after administration of ethanol, rats were anesthetized and experiments were terminated. The study revealed that administration of ethanol induced gastric ulcers in all animals and this effect was accompanied by the reduction in gastric blood flow and mucosal DNA synthesis. Moreover induction of gastric ulcer by ethanol significantly increased mucosal expression of mRNA for COX-2, IL-1? and TNF-?. Treatment with ghrelin significantly accelerated gastric ulcer healing. Therapeutic effect of ghrelin was associated with significant reversion of the ulcer-evoked decrease in mucosal blood flow and DNA synthesis. Ghrelin administration also caused the reduction in mucosal expression of mRNA for IL-1? and TNF-?. Addition of SC-560 slightly reduced the therapeutic effect of ghrelin in the healing of ethanol-induced ulcer and the ulcer area in rats treated SC-560 plus ghrelin was significantly smaller than that observed in rats treated with saline or SC-560 alone. Pretreatment with celecoxib, a COX-2 inhibitor, abolished therapeutic effect of ghrelin. We concluded that treatment with ghrelin increases healing rate of gastric ulcers evoked by ethanol and this effect is related to improvement in mucosal blood flow, an increase in mucosal cell proliferation, and reduction in mucosal expression of proinflammatory cytokines. Ghrelin is able to reverse a deleterious effect of COX-1 inhibitor on healing of ethanol-induced gastric ulcers. Activity of COX-2 is necessary for the therapeutic effect of ghrelin in healing of ethanol-induced gastric ulcers. PMID:24622834

Warzecha, Z; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Ginter, G; Ptak-Belowska, A; Dembinski, A

2014-02-01

232

Protective effect of HLA-DRB1 11 and predisposition of HLA-C 04 in the development of severe liver damage in Brazilian patients with chronic hepatitis C virus infection.  

PubMed

The objective of this study was to investigate human leucocyte antigen (HLA) genes in patients chronically infected with hepatitis C virus (HCV) and to analyse the possible role of these genes in the progression of chronic hepatitis C. One hundred and forty-five (145) Brazilian patients infected only with HCV genotype 1 were evaluated. HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1) typing were carried out by PCR-SSO, through Luminex technology. Associations were found with protection against development of liver damage by both DRB1 11 (5.0% versus 18.2%, P=0.0016, OR=0.23, CI 95% = 0.09-0.58; Pc=0.0208) and DRB1 11-DQA1 05-DQB1 03 haplotype (4.2% versus 15.3%, P=0.0032; OR = 0.24, CI 95% = 0.08-0.64). Liver damage was associated with HLA-C 04 in patients with <20 years of infection (38.4% versus 9.1%, P = 0.002, OR = 6.25, CI 95%=1.97-19.7; Pc=0.0238). It is concluded that HLA alleles can influence the development of liver damage in HCV type-1 chronically infected Brazilian patients. PMID:22803655

Marangon, A V; Silva, G F; de Moraes, C F V; Grotto, R M T; Pardini, M I M C; de Pauli, D S; Visentainer, J E L; Sell, A M; Moliterno, R A

2012-10-01

233

Microwave attenuation of ethanol-induced hypothermia: ethanol tolerance, time course, exposure duration, and dose response studies  

SciTech Connect

Four experiments were conducted to quantify the reported attenuation by microwave (MW) irradiation of ethanol-induced hypothermia. In one experiment rats were irradiated (continuous wave 2.45 GHz, specific absorption rate = 0.3 W/kg) or sham irradiated for 45 min, injected with 3.6 g/kg, 20% (v/v) ethanol (EtOH) or saline (NaCl) i.p.. Colonic temperature was monitored at 20-min intervals for 2 h. This procedure was repeated for 8 days to determine the rate of tolerance development to the hypothermic effect of ethanol. While MW irradiation did significantly attenuate EtOH-induced hypothermia, it did not enhance or retard the rate of tolerance development. To determine the duration of irradiation necessary to attenuate EtOH-induced hypothermia, groups of rats were irradiated or sham irradiated for 5, 15, 30, or 60 min prior to EtOH injection and subsequent temperature measurements. The attenuation was apparent only after 60 min of irradiation. To determine the duration of the attenuation effect after irradiation, rats were injected with EtOH or NaCl at 0, 30, 60, 120, or 480 min after 45 min of irradiation or sham irradiation. The attenuation effect was apparent among rats injected 0 to 30 min after irradiation and for the first 40 min for groups injected at 120 min. Additional rats were injected with NaCl or 0.9, 1.8, or 2.7 g/kg of EtOH i.p. following 45 min of irradiation or sham irradiation to determine if the attenuation effect depends on the dose of EtOH administered. Attenuation of EtOH-induced hypothermia was more apparent at lower doses of EtOH than at higher doses. These results indicate that the effect is an acute response to irradiation, and rule out several other potential explanations.

Hjeresen, D.L.; Francendese, A.; O'Donnell, J.M.

1988-01-01

234

Prophylactic effect of aqueous extract of Sesamum indicum seeds on ethanol-induced toxicity in male rats.  

PubMed

The liver is vulnerable to alcohol-related injury because it is the primary site of alcohol metabolism. Additionally, a number of potentially dangerous by-products are generated as alcohol is broken down in the liver. However, dietary supplements may prevent or relieve some of alcohol's deleterious effects. Therefore, this study was conducted to evaluate the prophylactic effect of aqueous extract of Sesamum indicum (SI) on ethanol induced toxicity in rats. Male Wistar albino rats were divided into control, ethanol, pre-treatment, simultaneous and post-treatment groups. In the prophylactic experiment, Sesamum indicum, (200 mg/kg body weight) was administered by oral gavage for 28 days; two hours before, simultaneously with or two hours after ethanol exposure. Toxicity was induced by administering 45% ethanol (4.8 g/kg bw) by oral gavage. Lipid peroxidation (TBARS) and reduced glutathione (GSH) levels and catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and gluthathione-S-transferase (GST) activities were then determined in the liver, serum triglyceride (TG) levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were monitored and histological examination was carried out. The results revealed that ethanol administration led to significant elevation of TBARS level while depleting in the level of GSH as well as CAT, GPx, SOD and GST activities. Similarly, TG level and ALT and AST activities were elevated. The SI pre-treated group significantly inhibited TBARS, restored GSH level, enhanced CAT, GPx, SOD and GST activities and significantly decreased the elevated level of serum TG, ALT and AST activities. SI treatment (simultaneously with ethanol) exhibited similar effects to those of the SI pre-treated groups, while the SI post-treated group did not show the same protection as the Pre-treated group. S. indicum possesses antioxidant and hepatoprotective properties, that eliminate the deleterious effects of toxic metabolites of ethanol. PMID:24611106

Oyinloye, B E; Nwozo, S O; Amah, G H; Awoyinka, A O; Ojo, O A; Ajiboye, B O; Tijani, H A

2014-02-01

235

Antioxidant Mechanism is Involved in the Gastroprotective Effects of Ozonized Sunflower Oil in Ethanol-Induced Ulcers in Rats  

PubMed Central

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.

Rodriguez, Zullyt B. Zamora; Alvarez, Ricardo Gonzalez; Guanche, Dailen; Merino, Nelson; Rosales, Frank Hernandez; Cepero, Silvia Menendez; Gonzalez, Yaima Alonso; Schulz, Siegfried

2007-01-01

236

Anandamide-CB1 Receptor Signaling Contributes to Postnatal Ethanol-Induced Neonatal Neurodegeneration, Adult Synaptic and Memory Deficits  

PubMed Central

The transient exposure of immature rodents to ethanol during postnatal day 7 (P7), which is comparable to the third trimester human pregnancy, induces synaptic dysfunctions. However, the molecular mechanisms underlying these dysfunctions are still poorly understood. Although the endocannabinoid system has been shown to be an important modulator of ethanol sensitivity in adult mice, its potential role in synaptic dysfunctions in mice exposed to ethanol during early brain development is not examined. In this study, we investigated the potential role of endocannabinoids and the cannabinoid receptor type 1 (CB1R) in neonatal neurodegeneration and adult synaptic dysfunctions in mice exposed to ethanol at P7. Ethanol treatment at P7, which induces neurodegeneration, increased anandamide (AEA) but not 2-arachidonylglycerol biosynthesis and CB1R protein expression in the hippocampus and cortex, two brain areas that are important for memory formation and storage, respectively. N-arachidonoyl phosphatidylethanolamine-phospholipase D (NAPE-PLD), glycerophosphodiesterase (GDE1) and CB1Rs protein expression were enhanced by transcriptional activation of the genes encoding NAPE-PLD, GDE1 and CB1R proteins respectively. In addition, ethanol inhibited ERK1/2 and AKT phosphorylation. The blockade of CB1Rs prior to ethanol treatment at P7 relieved ERK1/2 but not AKT phosphorylation and prevented neurodegeneration. CB1R knockout mice exhibited no ethanol-induced neurodegeneration and inhibition of ERK1/2-phosphorylation. The protective effects of CB1R blockade through pharmacological or genetic deletion resulted in normal adult synaptic plasticity and novel object recognition memory in mice exposed to ethanol at P7. The AEA/CB1R/pERK1/2 signaling pathway may be directly responsible for the synaptic and memory deficits associated with fetal alcohol spectrum disorders.

Subbanna, Shivakumar; Shivakumar, Madhu; Psychoyos, Delphine; Xie, Shan; Basavarajappa, Balapal S.

2013-01-01

237

Defining Hepatic Dysfunction Parameters in Two Models of Fatty Liver Disease in Zebrafish Larvae  

PubMed Central

Abstract Fatty liver disease in humans can progress from steatosis to hepatocellular injury, fibrosis, cirrhosis, and liver failure. We developed a series of straightforward assays to determine whether zebrafish larvae with either tunicamycin- or ethanol-induced steatosis develop hepatic dysfunction. We found altered expression of genes involved in acute phase response and hepatic function, and impaired hepatocyte secretion and disruption of canaliculi in both models, but glycogen deficiency in hepatocytes and dilation of hepatic vasculature occurred only in ethanol-treated larvae. Hepatic stellate cells (HSCs) become activated during liver injury and HSC numbers increased in both models. Whether the excess lipids in hepatocytes are a direct cause of hepatocyte dysfunction in fatty liver disease has not been defined. We prevented ethanol-induced steatosis by blocking activation of the sterol response element binding proteins (Srebps) using gonzombtps1 mutants and scap morphants and found that hepatocyte dysfunction persisted even in the absence of lipid accumulation. This suggests that lipotoxicity is not the primary cause of hepatic injury in these models of fatty liver disease. This study provides a panel of parameters to assess liver disease that can be easily applied to zebrafish mutants, transgenics, and for drug screening in which liver function is an important consideration.

Howarth, Deanna L.; Yin, Chunyue; Yeh, Karen

2013-01-01

238

Toxin-induced hepatic injury.  

PubMed

Toxins such as pharmaceuticals, herbals, foods, and supplements may lead to hepatic damage. This damage may range from nonspecific symptoms in the setting of liver test abnormalities to acute hepatic failure. The majority of severe cases of toxin-induced hepatic injury are caused by acetaminophen and ethanol. The most important step in the patient evaluation is to gather an extensive history that includes toxin exposure and exclude common causes of liver dysfunction. Patients whose hepatic dysfunction progresses to acute liver failure may benefit from transfer to a transplant service for further management. Currently, the mainstay in management for most exposures is discontinuing the offending agent. This manuscript will review the incidence, pathophysiology, diagnosis and management of the different forms of toxin-induced hepatic injury and exam in-depth the most common hepatic toxins. PMID:24275171

Lopez, Annette M; Hendrickson, Robert G

2014-02-01

239

Immunological Reactions in Viral Hepatitis.  

National Technical Information Service (NTIS)

Viral hepatitis sera (VHS) have been shown to possess mitosis-inhibiting (MI) and chromosome damaging (CD) activities on lymphocytes cultured in vitro in presence of phytohemagglutinin. These activities can be perpetuated by serial passage with filtered m...

B. Pernis

1970-01-01

240

Habituation to test procedure modulates the involvement of dopamine D2- but not D1-receptors in ethanol-induced locomotor stimulation in mice  

Microsoft Academic Search

Rationale  Novelty associated with behavioral testing has been shown to enhance psychostimulant- and morphine-induced locomotor stimulation.\\u000a Evidence has demonstrated that novelty increases dopamine (DA) activity, and habituation to a novel environment reduces such\\u000a activation. However, it is not clear whether novelty modulates ethanol-induced behavioral stimulation and whether DA plays\\u000a a role in this effect.\\u000a \\u000a \\u000a \\u000a Objectives  The present work sought to demonstrate a

Raúl Pastor; Marta Miquel; Carlos M. G. Aragon

2005-01-01

241

Hepatoprotective Activity of Elephantopus scaber on Alcohol-Induced Liver Damage in Mice.  

PubMed

Elephantopus scaber has been traditionally used as liver tonic. However, the protective effect of E. scaber on ethanol-induced liver damage is still unclear. In this study, we have compared the in vivo hepatoprotective effect of E. scaber with Phyllanthus niruri on the ethanol-induced liver damage in mice. The total phenolic and total flavanoid content of E. scaber ethanol extract were determined in this study. Accelerating serum biochemical profiles (including AST, ALT, ALP, triglyceride, and total bilirubin) associated with fat drop and necrotic body in the liver section were observed in the mice treated with ethanol. Low concentration of E. scaber was able to reduce serum biochemical profiles and the fat accumulation in the liver. Furthermore, high concentration of E. scaber and positive control P. niruri were able to revert the liver damage, which is comparable to the normal control. Added to this, E. scaber did not possess any oral acute toxicity on mice. These results suggest the potential effect of this extract as a hepatoprotective agent towards-ethanol induced liver damage without any oral acute toxicity effect. These activities might be contributed, or at least in part, by its high total phenolic and flavonoid contents. PMID:22973401

Ho, Wan Yong; Yeap, Swee Keong; Ho, Chai Ling; Abdul Rahim, Raha; Alitheen, Noorjahan Banu

2012-01-01

242

Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats  

PubMed Central

Chronic, excessive ethanol intake can increase retinoic acid (RA) catabolism by inducing cytochrome P450 2E1 (CYP2E1). Vitamin E (VE) is an antioxidant implicated in CYP2E1 inhibition. In the current study, we hypothesized that VE supplementation inhibits CYP2E1 and decreases RA catabolism, thereby preventing ethanol-induced hepatocyte hyperproliferation. For 1 month, four groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid ethanol (36% of the total calories) diet as follows: either ethanol alone (Alc group) or ethanol in combination with 0.1 mg/kg body wt of all-trans RA (Alc+RA group), 2 mg/kg body wt of VE (Alc+VE group), or both together (Alc+RA+VE group). Control rats were pair-fed a liquid diet with an isocaloric amount of maltodextrin instead of ethanol. The ethanol-fed groups had three-fold higher hepatic CYP2E1 levels, 50% lower hepatic RA levels, and significantly increased hepatocyte proliferation when compared with the controls. The ethanol-fed rats given VE had more than four-fold higher hepatic VE concentrations than did ethanol-fed rats without VE, but this did not prevent ethanol induction of CYP2E1, lower hepatic retinoid levels, or hepatocellular hyperproliferation. Further, VE supplementation could not prevent RA catabolism in liver microsomal fractions of the ethanol-fed rats in vitro. These results show that VE supplementation can neither inhibit ethanol-induced changes in RA catabolism nor prevent ethanol-induced hepatocyte hyperproliferation in the rat liver.

Chung, Jayong; Veeramachaneni, Sudipta; Liu, Chun; Mernitz, Heather; Russell, Robert M.; Wang, Xiang-Dong

2009-01-01

243

Hepatitis B and Hepatitis C in Pregnancy  

MedlinePLUS

What are hepatitis B and hepatitis C infections? Hepatitis B and hepatitis C are serious infections that affect the liver. Both diseases ... term illness. What extra risks are caused by hepatitis B and hepatitis C infections during pregnancy? Not only ...

244

Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats  

PubMed Central

Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant levels, and malondialdehyde (MDA) contents were evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose of 5?g/kg did not manifest any toxicological signs in rats. The extract promoted ulcer protection as ascertained by a significant reduction of the ulcer area. Furthermore, it exhibited a significant protection activity against gastric mucosal injury by preventing the depletion of antioxidant enzymes. The level of MDA was also limited in rat stomach tissues when compared with the ulcer control group. Immunohistochemistry showed upregulation of HSP70 protein and downregulation of BAX protein in rats pretreated with the extract. The aqueous extract of H. erinaceus protected gastric mucosa in our in vivo model. It is speculated that the bioactive compounds present in the extract may play a major role in gastroprotective activity.

Wong, Jing-Yang; Raman, Jegadeesh; Kuppusamy, Umah Rani; Sabaratnam, Vikineswary

2013-01-01

245

Induction of the Nrf2-driven antioxidant response by tert-butylhydroquinone prevents ethanol-induced apoptosis in cranial neural crest cells  

PubMed Central

Previous studies have shown that ethanol exposure causes apoptosis in cranial neural crest cells (NCCs), an ethanol-sensitive cell population implicated in Fetal Alcohol Spectrum Disorders (FASD). Additionally, induction of endogenous antioxidants through activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) has been shown to prevent oxidative stress and apoptosis in ethanol-exposed mouse embryos. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), an Nrf2 inducer, can protect NCCs against ethanol-induced apoptosis. Ethanol exposure was shown to cause a moderate increase in the protein expression of Nrf2 and its downstream antioxidants in the NCCs. Treatment of NCCs with tBHQ alone significantly increased the protein expression of Nrf2 and its downstream antioxidants and also significantly increased the activities of the antioxidant enzymes. In NCCs exposed to ethanol, the tBHQ-mediated antioxidant response prevented oxidative stress and apoptosis. These results clearly demonstrate that activation of Nrf2 signaling confers protection against ethanol-induced apoptosis in NCCs.

Yan, Dong; Dong, Jian; Sulik, Kathleen K.; Chen, Shao-yu

2010-01-01

246

Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats.  

PubMed

Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant levels, and malondialdehyde (MDA) contents were evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose of 5?g/kg did not manifest any toxicological signs in rats. The extract promoted ulcer protection as ascertained by a significant reduction of the ulcer area. Furthermore, it exhibited a significant protection activity against gastric mucosal injury by preventing the depletion of antioxidant enzymes. The level of MDA was also limited in rat stomach tissues when compared with the ulcer control group. Immunohistochemistry showed upregulation of HSP70 protein and downregulation of BAX protein in rats pretreated with the extract. The aqueous extract of H. erinaceus protected gastric mucosa in our in vivo model. It is speculated that the bioactive compounds present in the extract may play a major role in gastroprotective activity. PMID:24302966

Wong, Jing-Yang; Abdulla, Mahmood Ameen; Raman, Jegadeesh; Phan, Chia-Wei; Kuppusamy, Umah Rani; Golbabapour, Shahram; Sabaratnam, Vikineswary

2013-01-01

247

The effects of gonadectomy on sex- and age-typical responses to novelty and ethanol-induced social inhibition in adult male and female Sprague-Dawley rats.  

PubMed

Sex- and age-typical responses to ethanol and novel stimuli tend to emerge postpubertally, suggesting a potential organizational or activational role for pubertal hormones in these behaviors. To test this possibility, male and female rats were gonadectomized (GX) or received sham gonadectomy (SH) either prepubertally on postnatal day (P) 23 (early) or in adulthood on P70 (late). Animals were tested as adults for response to novelty and, on the following day, challenged with either saline or ethanol (1g/kg) prior to social interaction testing with an unfamiliar partner in a familiar setting under low light conditions. Gonadectomy did not influence ethanol-induced social inhibition in either sex, but instead altered the microstructure of social behavior, with GX animals exhibiting proportionally less time in social investigation and proportionally more time in contact behavior than SH animals, regardless of age of gonadectomy. The early sham surgical manipulation process itself influenced social motivation, with early SH surgery eliminating ethanol-induced decreases in social preference in both sexes. Response to novelty was unaffected by gonadectomy, but was suppressed in early compared to late SH manipulated animals. These results suggest that adult-typical responses to ethanol and novelty-directed behaviors are little influenced by gonadal hormones during puberty or in adulthood. However, the experience of surgical manipulation itself during development exerts behavioral and pharmacological consequences that last into adulthood. PMID:22036699

Vetter-O'Hagen, Courtney S; Spear, Linda P

2012-02-01

248

Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors  

PubMed Central

Background The fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate. Results Ethanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid. Conclusion The reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation.

Santillano, Daniel R; Kumar, Leena S; Prock, Terasa L; Camarillo, Cynthia; Tingling, Joseph D; Miranda, Rajesh C

2005-01-01

249

Hepatitis virus panel  

MedlinePLUS

Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg) -- you have ...

250

Serum Iron Levels and Hepatic Iron Overload in Nonalcoholic Steatohepatitis and Chronic Viral Hepatitis  

Microsoft Academic Search

Our objective was to determine the effect of serum iron levels and hepatic iron overload on hepatocellular damage in nonalcoholic steatohepatitis (NASH) and to compare this with chronic viral hepatitis. Twenty-five patients who had elevated transaminase levels on at least two occasions, without any evidence of viral and autoimmune hepatitis and diabetes, without a history of significant alcohol use, and

Suleyman Uraz; Cem Aygun; Abdullah Sonsuz; Gulsen Ozbay

2005-01-01

251

Mangiferin, a Natural Xanthone, Protects Murine Liver in Pb(II) Induced Hepatic Damage and Cell Death via MAP Kinase, NF-?B and Mitochondria Dependent Pathways  

PubMed Central

One of the most well-known naturally occurring environmental heavy metals, lead (Pb) has been reported to cause liver injury and cellular apoptosis by disturbing the prooxidant-antioxidant balance via oxidative stress. Several studies, on the other hand, reported that mangiferin, a naturally occurring xanthone, has been used for a broad range of therapeutic purposes. In the present study, we, therefore, investigated the molecular mechanisms of the protective action of mangiferin against lead-induced hepatic pathophysiology. Lead [Pb(II)] in the form of Pb(NO3)2 (at a dose of 5 mg/kg body weight, 6 days, orally) induced oxidative stress, hepatic dysfunction and cell death in murine liver. Post treatment of mangiferin at a dose of 100 mg/kg body weight (6 days, orally), on the other hand, diminished the formation of reactive oxygen species (ROS) and reduced the levels of serum marker enzymes [alanine aminotranferase (ALT) and alkaline phosphatase (ALP)]. Mangiferin also reduced Pb(II) induced alterations in antioxidant machineries, restored the mitochondrial membrane potential as well as mutual regulation of Bcl-2/Bax. Furthermore, mangiferin inhibited Pb(II)-induced activation of mitogen-activated protein kinases (MAPKs) (phospho-ERK 1/2, phosphor-JNK phospho- p38), nuclear translocation of NF-?B and apoptotic cell death as was evidenced by DNA fragmentation, FACS analysis and histological assessment. In vitro studies using hepatocytes as the working model also showed the protective effect of mangiferin in Pb(II) induced cytotoxicity. All these beneficial effects of mangiferin contributes to the considerable reduction of apoptotic hepatic cell death induced by Pb(II). Overall results demonstrate that mangiferin exhibit both antioxidative and antiapoptotic properties and protects the organ in Pb(II) induced hepatic dysfunction.

Pal, Pabitra Bikash; Sinha, Krishnendu; Sil, Parames C.

2013-01-01

252

Ethanol-induced HO-1 and NQO1 Are Differentially Regulated by HIF-1? and Nrf2 to Attenuate Inflammatory Cytokine Expression*  

PubMed Central

Oxidative stress plays an important role in alcohol-induced inflammation and liver injury. Relatively less is known about how Kupffer cells respond to oxidative stress-induced expression of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1) to blunt inflammation and liver injury. We showed that Kupffer cells from ethanol-fed rats and ethanol-treated rat Kupffer cells and THP-1 cells displayed increased mRNA expression of HO-1, NQO1, and hypoxia-inducible factor-1? (HIF-1?). Our studies showed that silencing with HIF-1? and JNK-1 siRNAs attenuated ethanol-mediated mRNA expression of HO-1, but not NQO1, whereas Nrf2 siRNA attenuated the mRNA expression of both HO-1 and NQO1. Additionally, JunD but not JunB formed an activator protein-1 (AP-1) oligomeric complex to augment HO-1 promoter activity. Ethanol-induced HO-1 transcription involved antioxidant response elements, hypoxia-response elements, and an AP-1 binding motif in its promoter, as demonstrated by mutation analysis of the promoter, EMSA, and ChIP. Furthermore, livers of ethanol-fed c-Junfl/fl mice showed reduced levels of mRNA for HO-1 but not of NQO1 compared with ethanol-fed control rats, supporting the role of c-Jun or the AP-1 transcriptional complex in ethanol-induced HO-1 expression. Additionally, attenuation of HO-1 levels in ethanol-fed c-Junfl/fl mice led to increased proinflammatory cytokine expression in the liver. These results for the first time show that ethanol regulates HO-1 and NQO1 transcription by different signaling pathways. Additionally, up-regulation of HO-1 protects the liver from excessive formation of inflammatory cytokines. These studies provide novel therapeutic targets to ameliorate alcohol induced inflammation and liver injury.

Yeligar, Samantha M.; Machida, Keigo; Kalra, Vijay K.

2010-01-01

253

Viral Hepatitis  

MedlinePLUS

... information Breastfeeding HIV/AIDS Illnesses and disabilities Pregnancy Sexually transmitted infections fact sheet What is hepatitis? What are the ... Hepatitis B prevention Get vaccinated. As with other sexually transmitted infections, limit sexual partners and use latex condoms to ...

254

Hepatic Cysts.  

PubMed

Treatment of hepatic cysts should be considered only for those patients who are symptomatic. For simple cysts, percutaneous aspiration invariably leads to recurrence; laparoscopic deroofing is usually curative. Open deroofing (fenestration) should be reserved for cysts inaccessible by laparoscopy. Percutaneous instillation of sclerosing agents (ethanol, iophendylate, minocycline) into nonbiliary and nonparasitic cysts is an alternative therapeutic option in certain cases. Due to increased morbidity, hepatic resection should be reserved for polycystic liver disease, diffuse hepatic involvement, or recurrence after a deroofing procedure. Patients with congenital fibropolycystic disorders (eg, congenital hepatic fibrosis) with evidence of hepatic decompensation, should be considered for liver transplantation. For hepatic hydatid cysts, simple cystectomy or the PAIR (puncture, aspirate, inject, and reaspirate) technique with albendazole treatment have been shown to be equally successful. In the case of alveolar echinococcosis, hepatic resection and liver transplantation are the only effective modalities for localized and extensive hepatic disease, respectively. PMID:11096603

Kaul; Friedenberg; Rothstein

2000-12-01

255

Hepatitis A  

MedlinePLUS

... Working in a health care, food, or sewage industry Other common hepatitis virus infections include hepatitis B ... steps to protect against getting the disease: Avoid dairy products. Avoid raw or undercooked meat and fish. ...

256

Hepatitis A FAQs  

MedlinePLUS

... C. What is the difference between Hepatitis A, Hepatitis B, and Hepatitis C? Hepatitis A , Hepatitis B , and Hepatitis C are diseases caused by three ... People with Hepatitis A usually improve without treatment. Hepatitis B and Hepatitis C can also begin as acute ...

257

Hepatitis C FAQs  

MedlinePLUS

... C. What is the difference between Hepatitis A, Hepatitis B, and Hepatitis C? Hepatitis A , Hepatitis B , and Hepatitis C are diseases caused by three ... People with Hepatitis A usually improve without treatment. Hepatitis B and Hepatitis C can also begin as acute ...

258

Update on chronic viral hepatitis  

PubMed Central

Many recent and significant advances in the field of chronic viral hepatitis, including therapy, suggest that an update on chronic hepatitis is timely.?Chronic hepatitis B virus infection remains a significant worldwide cause of liver cirrhosis and hepatocellular carcinoma, despite the wide availability of a long established and effective vaccine. Transmission occurs via perinatal, sexual, and parenteral routes (particularly intravenous drug abuse and although blood products still carry a risk, this is now extremely low in Western countries). Only a minority of infected adult cases develop chronic hepatitis but in children under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic liver injury ranges from mild inflammation to end stage liver cirrhosis. Interferon alfa has been the mainstay of treatment for patients with active disease but nucleoside analogues (lamivudine and adefovir) are now available with similar efficacy. Patients with end stage liver disease and hepatocellular carcinoma can be offered transplantation but infection in the graft is commonplace. The combination of hepatitis B immunoglobulin and newer antiviral drugs reduce the incidence and severity of graft infection significantly.?The hepatitis C virus epidemic of the latter half of the 20th century now affects more than 1% of populations worldwide. This RNA virus is spread parenterally and is becoming the leading indication for liver transplantation. The majority of patients develop chronic hepatitis, which may be progressive, evolving to significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20% cases after decades. Treatment with the combination of interferon alfa and ribavirin is successful in up to 40% cases. Liver transplantation is a therapeutic option for some but graft infection is universal and often complicated by progressive liver fibrosis. A vaccine remains a remote prospect so that prevention is crucial.?Hepatitis D virus infection occurs on a background of hepatitis B virus infection and can also cause liver damage. The response to antiviral therapy is poor.?The newer "hepatitis" viruses G and TT do not cause significant liver injury.???Keywords: hepatitis

Walsh, K; Alexander, G

2001-01-01

259

Serum Apoptosis Markers Related to Liver Damage in Chronic Hepatitis C: sFas as a Marker of Advanced Fibrosis in Children and Adults While M30 of Severe Steatosis Only in Children  

PubMed Central

Background Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC. Methods Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured. Results sFas was associated with fibrosis severity in pediatric (significant fibrosis p?=?0.03, advanced fibrosis p?=?0.01) and adult patients (advanced fibrosis p?=?0.02). M30 levels were elevated in pediatric patients with severe steatosis (p?=?0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p?=?0.03) and they were associated with hepatitis severity (p?=?0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833). Conclusions Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children.

Valva, Pamela; Casciato, Paola; Lezama, Carol; Galoppo, Marcela; Gadano, Adrian; Galdame, Omar; Galoppo, Maria Cristina; Mullen, Eduardo; De Matteo, Elena; Preciado, Maria Victoria

2013-01-01

260

Hepatic mRNA, microRNA, and miR-34a-Target responses in mice after 28 days exposure to doses of benzo(a)pyrene that elicit DNA damage and mutation  

PubMed Central

Benzo(a)pyrene (BaP) is a mutagenic carcinogen that is ubiquitous in our environment. To better understand the toxic effects of BaP and to explore the relationship between toxicity and toxicogenomics profiles, we assessed global mRNA and microRNA (miRNA) expression in Muta™Mouse. Adult male mice were exposed by oral gavage to 25, 50, and 75 mg/kg/day BaP for 28 days. Liver tissue was collected 3 days following the last treatment. Initially, we established that exposure to BaP led to the formation of hepatic DNA adducts and mutations in the lacZ transgene of the Muta™Mouse. We then analyzed hepatic gene expression profiles. Microarray analysis of liver samples revealed 134 differentially expressed transcripts (adjusted P < 0.05; fold changes > 1.5). The mRNAs most affected were involved in xenobiotic metabolism, immune response, and the downstream targets of p53. In this study, we found a significant 2.0 and 3.6-fold increase following exposure to 50 and 75 mg/kg/day BaP, respectively, relative to controls for miR-34a. This miRNA is involved in p53 response. No other significant changes in miRNAs were observed. The protein levels of five experimentally confirmed miR-34a targets were examined, and no major down-regulation was present. The results suggest that liver miRNAs are largely unresponsive to BaP doses that cause both DNA adducts and mutations. In summary, the validated miRNA and mRNA expression profiles following 28 day BaP exposure reflect a DNA damage response and effects on the cell cycle, consistent with the observed increases in DNA adducts and mutations. Environ. Mol. Mutagen., 2012. © 2011 Crown in the right of Canada

Malik, Amal I; Williams, Andrew; Lemieux, Christine L; White, Paul A; Yauk, Carole L

2012-01-01

261

Evaluation of the antioxidant effects of Ziziphus mauritiana Lam. Leaf extracts against chronic ethanol-induced hepatotoxicity in rat liver.  

PubMed

Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1 ml/100 g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pre-treatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation. PMID:20162053

Dahiru, D; Obidoa, O

2007-01-01

262

Chronic hepatitis induced by Jin Bu Huan  

Microsoft Academic Search

Background\\/Aimds: Jin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne

Antonino Picciotto; Nadia Campo; Renata Brizzolara; Rosella Giusto; Gianluca Guido; Nicoletta Sinelli; Gabriella Lapertosa; Guido Celle

1998-01-01

263

Hepatitis B: Progress in the last 15 years  

Microsoft Academic Search

1. Patients undergoing orthotopic liver transplantation (OLT) for hepatitis B without effective prophylaxis have a high risk for recurrent infection and severe graft damage, leading to death or re-OLT. 2. Long-term prophylaxis with hepatitis B immune globulin (HBIg) significantly reduces the risk for hepatitis B virus (HBV) recurrence and increases survival. Patients with detectable HBV DNA at the time of

Federico G. Villamil

2002-01-01

264

Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance  

PubMed Central

Insulin resistance is a major risk factor for type 2 diabetes mellitus. The protein encoded by the sirtuin 1 (Sirt1) gene, which is a mouse homolog of yeast Sir2, is implicated in the regulation of glucose metabolism and insulin sensitivity; however, the underlying mechanism remains elusive. Here, using mice with a liver-specific null mutation of Sirt1, we have identified a signaling pathway involving Sirt1, Rictor (a component of mTOR complex 2 [mTorc2]), Akt, and Foxo1 that regulates gluconeogenesis. We found that Sirt1 positively regulates transcription of the gene encoding Rictor, triggering a cascade of phosphorylation of Akt at S473 and Foxo1 at S253 and resulting in decreased transcription of the gluconeogenic genes glucose-6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (Pepck). Liver-specific Sirt1 deficiency caused hepatic glucose overproduction, chronic hyperglycemia, and increased ROS production. This oxidative stress disrupted mTorc2 and impaired mTorc2/Akt signaling in other insulin-sensitive organs, leading to insulin resistance that could be largely reversed with antioxidant treatment. These data delineate a pathway through which Sirt1 maintains insulin sensitivity and suggest that treatment with antioxidants might provide protection against progressive insulin resistance in older human populations.

Wang, Rui-Hong; Kim, Hyun-Seok; Xiao, Cuiying; Xu, Xiaoling; Gavrilova, Oksana; Deng, Chu-Xia

2011-01-01

265

Hepatitis B Vaccine  

MedlinePLUS

... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

266

Hepatic incidentalomas.  

PubMed

Recent advances in multidetector-row computed tomography, magnetic resonance imaging, and ultrasonography have led to the detection of incidental hepatic lesions in both the oncology and nononcology patient population that in the past remained undiscovered. These incidental hepatic lesions have created a management dilemma for both clinicians and radiologists. In this review, guidelines concerning the diagnosis and management of some of the more common hepatic incidentalomas are presented. PMID:21333779

Gore, Richard M; Newmark, Geraldine M; Thakrar, Kiran H; Mehta, Uday K; Berlin, Jonathan W

2011-03-01

267

Hepatic ischemia  

MedlinePLUS

... ischemia. Such conditions may include: Abnormal heart rhythms Dehydration Heart failure Infection Severe bleeding Other causes may include: Blood clots in the main artery to the liver (hepatic ...

268

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

PubMed Central

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.

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

269

Hepatic cavitation  

Microsoft Academic Search

Sonographically visible microbubbles attributable to cavitation effects have been observed in bile (within the gallbladder), in hepatic vessels, and within the liver of patients undergoing biliary lithotripsy. Cavitation effects are believed to contribute to stone fragmentation and possibly tissue injury during lithotripsy. To study the latter, the relationship between intraparenchymal hepatic cavitation and serum transaminase activity and clinical follow-up was

Leslie E. Forer; William J. Davros; Joanne Goldberg; Firas Al-Kawas; Brian S. Garra; Wendelin Hayes; Robert K. Zeman

1992-01-01

270

Hepatitis B  

MedlinePLUS

By 1970, the hepatitis B virus had been identified and shown to be a major cause of acute and chronic liver disease. Reliable but ... insensitive tests for the virus were newly available. Hepatitis B was the most common cause of acute liver ...

271

Hepatitis in Dengue Shock Syndrome  

Microsoft Academic Search

Dengue fever is the most frequent arbovirus disease in the world and the most important one in terms of morbidity and mortality. Atypical manifestations of dengue have become commonplace during the last few years, including hepatic damage, which manifests mainly by pain in the right hypochondrium and an increase in the levels of aminotransferases. We describe a case of acute

Luiz José de Souza; Helder Gonçalves Carneiro; Joăo Tadeu Damian Souto Filho; Thiago Ferreira de Souza; Vitor Azevedo Côrtes; Carlos Gicovate Neto; Diogo Assed Bastos; Edno Wallace da Silva Siqueira

2002-01-01

272

Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model  

PubMed Central

Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for ?-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-?1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-?1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.

Noh, Dong-Hyung; Lee, Eun-Joo; Kim, Ah-Young; Lee, Eun-Mi; Min, Chang-Woo; Kang, Kyung-Ku; Lee, Myeong-Mi; Kim, Sang-Hyeob; Sung, Soo-Eun; Hwang, Meeyul; Yu, Dae-Yeul; Jeong, Kyu-Shik

2014-01-01

273

Alcohol induced hepatic degeneration in a hepatitis C virus core protein transgenic mouse model.  

PubMed

Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for ?-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-?1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-?1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection. PMID:24608925

Noh, Dong-Hyung; Lee, Eun-Joo; Kim, Ah-Young; Lee, Eun-Mi; Min, Chang-Woo; Kang, Kyung-Ku; Lee, Myeong-Mi; Kim, Sang-Hyeob; Sung, Soo-Eun; Hwang, Meeyul; Yu, Dae-Yeul; Jeong, Kyu-Shik

2014-01-01

274

Organ damage and hepatic lipid accumulation in carp (Cyprinus carpio L.) after feed-borne exposure to the mycotoxin, deoxynivalenol (DON).  

PubMed

Deoxynivalenol (DON) frequently contaminates animal feed, including fish feed used in aquaculture. This study intends to further investigate the effects of DON on carp (Cyprinus carpio L.) at concentrations representative for commercial fish feeds. Experimental feeding with 352, 619 or 953 ?g DON kg(-1) feed resulted in unaltered growth performance of fish during six weeks of experimentation, but increased lipid peroxidation was observed in liver, head kidney and spleen after feeding of fish with the highest DON concentration. These effects of DON were mostly reversible by two weeks of feeding the uncontaminated control diet. Histopathological scoring revealed increased liver damage in DON-treated fish, which persisted even after the recovery phase. At the highest DON concentration, significantly more fat, and consequently, increased energy content, was found in whole fish body homogenates. This suggests that DON affects nutrient metabolism in carp. Changes of lactate dehydrogenase (LDH) activity in kidneys and muscle and high lactate levels in serum indicate an effect of DON on anaerobic metabolism. Serum albumin was reduced by feeding the medium and a high dosage of DON, probably due to the ribotoxic action of DON. Thus, the present study provides evidence of the effects of DON on liver function and metabolism. PMID:24566729

Pietsch, Constanze; Schulz, Carsten; Rovira, Pere; Kloas, Werner; Burkhardt-Holm, Patricia

2014-02-01

275

The influence of 1800 MHz GSM-like signals on hepatic oxidative DNA and lipid damage in nonpregnant, pregnant, and newly born rabbits.  

PubMed

The aim of our study is to evaluate the possible biological effects of whole-body 1800 MHz GSM-like radiofrequency (RF) radiation exposure on liver oxidative DNA damage and lipid peroxidation levels in nonpregnant, pregnant New Zealand White rabbits, and in their newly borns. Eighteen nonpregnant and pregnant rabbits were used and randomly divided into four groups which were composed of nine rabbits: (i) Group I (nonpregnant control), (ii) Group II (nonpregnant-RF exposed), (iii) Group III (pregnant control), (iv) Group IV (pregnant-RF exposed). Newborns of the pregnant rabbits were also divided into two groups: (v) Group V (newborns of Group III) and (vi) Group VI (newborns of Group III). 1800 MHz GSM-like RF radiation whole-body exposure (15 min/day for a week) was applied to Group II and Group IV. No significant differences were found in liver 8 OHdG/10(6) dG levels of exposure groups (Group II and Group IV) compared to controls (Group I and Group III). However, in Group II and Group IV malondialdehyde (MDA) and ferrous oxidation in xylenol orange (FOX) levels were increased compared to Group I (P < 0.05, Mann-Whitney). No significant differences were found in liver tissue of 8 OHdG/10(6) dG and MDA levels between Group VI and Group V (P > 0.05, Mann-Whitney) while liver FOX levels were found significantly increased in Group VI with respect to Group V (P < 0.05, Mann-Whitney). Consequently, the whole-body 1800 MHz GSM-like RF radiation exposure may lead to oxidative destruction as being indicators of subsequent reactions that occur to form oxygen toxicity in tissues. PMID:19851891

Tomruk, Arin; Guler, Goknur; Dincel, Aylin Sepici

2010-01-01

276

Hepatic encephalopathy.  

PubMed

Hepatic encephalopathy is a serious and potentially fatal complication of both acute and chronic liver disease, arising as a result of hepatocellular failure, cirrhosis and/or portal-systemic shunting (Ferenci et al, 2002). It reflects a broad spectrum of neuropsychiatric abnormalities, encompassing a range of defects in psychomotor, locomotive, cognitive, emotional and behavioural functions (Prakash and Mullen, 2010). Hepatic encephalopathy is either overt or minimal. While overt hepatic encephalopathy can be diagnosed using bedside clinical tests, minimal hepatic encephalopathy is clinically invisible and requires psychometric testing to diagnose. The rising prevalence of end-stage viral hepatitis-related liver disease, coupled with the growing problem of alcoholic and non-alcoholic fatty liver disease, has significantly increased the burden of disease from cirrhosis (Mooney et al, 2007; Fleming et al, 2008), so recognition and appropriate management of the manifestations of decompensating cirrhosis (including hepatic encephalopathy) is essential. Hepatic encephalopathy has a substantial societal burden because of its impact on survival, quality of life and daily functioning, including an impaired ability to drive, leaving patients especially vulnerable to road traffic accidents (Ferenci et al, 2002; Prakash and Mullen, 2010). PMID:22504749

Patel, D; McPhail, M J W; Cobbold, J F L; Taylor-Robinson, S D

2012-02-01

277

Cytotoxic and DNA-damaging effects of diterpenoid quinones from the roots of Salvia officinalis L. on colonic and hepatic human cells cultured in vitro.  

PubMed

Three diterpenoid quinones (royleanone- SAR 3, horminone- SAR 26, and acetyl horminone- SAR 43) isolated from the roots of Salvia officinalis L. were tested for their cytotoxic and DNA-damaging activity in human colon carcinoma cells Caco-2 and human hepatoma cells HepG2 cultured in vitro. Cytotoxicity was measured by the trypan blue exclusion technique and induction of apoptosis was evaluated by flow immunofluorocytometry after 30-300 min. exposure of HepG2 and Caco-2 cells to diterpenoid quinones and following 24 hr post-incubation in the culture medium. Induction of DNA breaks was measured after 60 min. exposure of cells to different concentrations of the compounds studied by the alkaline elution of DNA and by the Comet assay. Though all the quinones tested decreased the viability of the cells studied proportionally to the concentration and to the time of treatment (cytotoxicity= 30-60%), the increased level of apoptotic nuclei comparable to the level of apoptotic nuclei induced by a topoisomerase I inhibitor was proved only in HepG2 cells treated with 1x10(-4) mol/l SAR 26 or SAR 43. Either no or marginal increase of the level of apoptotic nuclei was observed in SAR 3-treated HepG2 cells and in SAR 3-, SAR 26- or SAR 43-treated Caco-2 cells. All compounds tested induced creation of DNA strand breaks in both cell types at concentrations >1x10(-7)-1x10(-6) mol/l. The occurrence of DNA strand breaks at different pH values as well as the kinetics of DNA breaks rejoining were evaluated only in colonic cells Caco-2. The Comet assay processed in parallel at pH 13.0 and pH 12.1 showed that strand breaks detected in SARs-treated colonic Caco-2 cells originated from alkali-labile sites, as induced DNA lesions were converted to DNA strand breaks only under strong alkaline conditions. The kinetics of DNA rejoining revealed that SARs-induced DNA breaks were repaired very slowly. PMID:15228500

Slamenová, Darina; Masterová, Irena; Lábaj, Juraj; Horváthová, Eva; Kubala, Pavol; Jakubíková, Jana; Wsólová, Ladislava

2004-06-01

278

Hepatic Encephalopathy  

PubMed Central

Chronic liver disease and cirrhosis affect hundreds of millions of patients all over the world. The majority of patients with cirrhosis will eventually develop complications related to portal hypertension. One of these recurrent and difficult to treat complications is hepatic encephalopathy. Studies have indicated that overt hepatic encephalopathy affects 30 to 45% of patients with cirrhosis and a higher percentage may be affected by minimal degree of encephalopathy. All of these factors add to the impact of hepatic encephalopathy on the healthcare system and presents a major challenge to the gastroenterologist, hospitalist and primary care physician.

Bleibel, Wissam; Al-Osaimi, Abdullah M. S.

2012-01-01

279

Greater Ethanol-Induced Locomotor Activation in DBA/2J versus C57BL/6J Mice Is Not Predicted by Presynaptic Striatal Dopamine Dynamics  

PubMed Central

A large body of research has aimed to determine the neurochemical factors driving differential sensitivity to ethanol between individuals in an attempt to find predictors of ethanol abuse vulnerability. Here we find that the locomotor activating effects of ethanol are markedly greater in DBA/2J compared to C57BL/6J mice, although it is unclear as to what neurochemical differences between strains mediate this behavior. Dopamine elevations in the nucleus accumbens and caudate-putamen regulate locomotor behavior for most drugs, including ethanol; thus, we aimed to determine if differences in these regions predict strain differences in ethanol-induced locomotor activity. Previous studies suggest that ethanol interacts with the dopamine transporter, potentially mediating its locomotor activating effects; however, we found that ethanol had no effects on dopamine uptake in either strain. Ex vivo voltammetry allows for the determination of ethanol effects on presynaptic dopamine terminals, independent of drug-induced changes in firing rates of afferent inputs from either dopamine neurons or other neurotransmitter systems. However, differences in striatal dopamine dynamics did not predict the locomotor-activating effects of ethanol, since the inhibitory effects of ethanol on dopamine release were similar between strains. There were differences in presynaptic dopamine function between strains, with faster dopamine clearance in the caudate-putamen of DBA/2J mice; however, it is unclear how this difference relates to locomotor behavior. Because of the role of the dopamine system in reinforcement and reward learning, differences in dopamine signaling between the strains could have implications for addiction-related behaviors that extend beyond ethanol effects in the striatum.

Rose, Jamie H.; Calipari, Erin S.; Mathews, Tiffany A.; Jones, Sara R.

2013-01-01

280

MT-7716, a novel selective nonpeptidergic NOP receptor agonist, effectively blocks ethanol-induced increase in GABAergic transmission in the rat central amygdala.  

PubMed

The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. A large body of evidence shows that Nociceptin/Orphanin FQ (N/OFQ) regulates ethanol intake and anxiety-like behavior. In the rat, ethanol significantly augments CeA GABA release, whereas N/OFQ diminishes it. Using electrophysiological techniques in an in vitro slice preparation, in this study we investigated the effects of a nonpeptidergic NOP receptor agonist, MT-7716 [(R)-2-3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl-N-methylacetamide hydrochloride hydrate], and its interaction with ethanol on GABAergic transmission in CeA slices of naďve rats. We found that MT-7716 dose-dependently (100-1000 nM) diminished evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) and increased paired-pulse facilitation (PPF) ratio of these evoked IPSPs, suggesting a presynaptic site of action of the MT-7716 by decreasing GABA release at CeA synapses. The presynaptic action of MT-7716 was also supported by the significant decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) induced by the nociceptin receptor (NOP) agonist. Interestingly, MT-7716 prevented the ethanol-induced augmentation of evoked IPSPs. A putative selective NOP antagonist, [Nphe1]Nociceptin(1-13)NH2, totally prevented the MT-7716-induced inhibition of IPSP amplitudes indicating that MT-7716 exerts its effect through NOPs. These data provide support for an interaction between the nociceptin and GABAergic systems in the CeA and for the anti-alcohol properties of the NOP activation. The development of a synthetic nonpeptidergic NOP receptor agonist such as MT-7716 may represent a useful therapeutic target for alcoholism. PMID:24600360

Kallupi, Marsida; Oleata, Christopher S; Luu, George; Teshima, Koji; Ciccocioppo, Roberto; Roberto, Marisa

2014-01-01

281

Meconium Fatty Acid Ethyl Esters as Biomarkers of Late Gestational Ethanol Exposure and Indicator of Ethanol-Induced Multi-Organ Injury in Fetal Sheep  

PubMed Central

Background Meconium fatty acid ethyl esters (FAEE) constitute a biomarker of heavy fetal ethanol exposure. Our objective was to measure meconium FAEE in fetal sheep following daily, relatively moderate-dose ethanol exposure in late gestation, and to evaluate their utility in identifying fetal organ-system injury. Methods Pregnant ewes received ethanol (0.75 g/kg; n?=?14) or saline (n?=?8) via 1-h IV infusion daily during the third trimester equivalent, while additional pregnant sheep served as untreated controls (n?=?6). The daily ethanol regimen produced similar maximal maternal and fetal plasma ethanol concentrations of 0.11–0.12 g/dL. Ewes and fetuses were euthanized shortly before term, and meconium was collected and analyzed for FAEE (ethyl palmitate, stearate, linoleate, and oleate). Results Meconium total FAEE concentration was significantly higher in ethanol-exposed fetuses compared with controls, and a positive cut-off of 0.0285 nmol total FAEE/g meconium had 93.3% sensitivity and specificity for detecting fetal ethanol exposure. When the studied animals (ethanol-exposed and controls) were classified according to meconium FAEE concentration, FAEE-positive and FAEE-negative groups frequently differed with respect to previously examined pathological endpoints, including nephron endowment, lung collagen deposition, cardiomyocyte maturation, and tropoelastin gene expression in cerebral vessels. Furthermore, in all studied animals as a group (ethanol-exposed and controls combined), meconium FAEE concentration was correlated with many of these pathological endpoints in fetal organs. Conclusions We conclude that, in fetal sheep, meconium FAEE could serve as a biomarker of daily ethanol exposure in late gestation and could identify fetuses with subtle ethanol-induced toxic effects in various organs. This study illustrates the potential for using meconium FAEE to identify neonates at risk for dysfunction of major organs following in-utero ethanol exposure that does not result in overt physical signs of ethanol teratogenicity.

Zelner, Irene; Kenna, Kelly; Brien, James F.; Bocking, Alan; Harding, Richard; Walker, David; Koren, Gideon

2013-01-01

282

Brain region specific modulation of ethanol-induced depression of GABAergic neurons in the brain reward system by the nicotine receptor antagonist mecamylamine.  

PubMed

The mechanisms underlying ethanol-induced activation of the mesolimbic dopamine system are not fully understood, but increased extracellular dopamine in the nucleus accumbens (nAc) has been shown to involve nicotinic acetylcholine receptors (nAChRs). Basal activity of dopaminergic neurons in the ventral tegmental area (VTA) is under the influence of GABAergic neurotransmission, and the aim of this study was to characterize the involvement of nAChRs in mediating acute ethanol effects on GABAergic activity in subregions of the brain reward system. Multi-electrode in vivo recordings were made in the VTA and nAc of awake and behaving C57BL6/J mice receiving intraperitoneal injections of saline or ethanol (2.0 g/kg), combined with, or without, pre-injection of the non-competitive nAChR antagonist mecamylamine (1.0 mg/kg). Ethanol significantly decreased the activity of quinpirole-insensitive slow-spiking and fast-spiking units in both the VTA and the nAc as compared to saline injection. Pre-treatment with mecamylamine inhibited the rate-inhibiting properties of ethanol in the VTA, but not in the nAc. The data presented here show that ethanol depresses the activity of quinpirole-insensitive, putative GABAergic neurons, in the mesolimbic dopamine system of mice, and that nAChRs contribute to this modulation. This finding, taken together with previous microdialysis studies, supports an involvement of GABAergic neurons and nAChRs in ethanol's interaction with the mesolimbic dopamine system. PMID:24961541

Adermark, Louise; Söderpalm, Bo; Burkhardt, John M

2014-08-01

283

Cerebroprotective effect of isolated harmine alkaloids extracts of seeds of Peganum harmala L. on sodium nitrite-induced hypoxia and ethanol-induced neurodegeneration in young mice.  

PubMed

The aim of the study was to isolate the harmine alkaloids from the seeds of Peganum harmala (TAPH) and its cerebroprotective effect on cognitive deficit mice. The tested doses of TAPH were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models. The TAPH was found to be non-neurotoxic and Psychoactive by preventing the motor impairment and increasing the locomotion activity of animals in Rota rod and Actophotometer respectively. TAPH (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. In Elevated Plus Maze (EPM) and Passive Shock Avoidance paradigm (PSA) the TAPH shown improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transverse Latency Time (TLT) and increasing the Step Down Latency (SDL), respectively in dose dependent manner. The results were well supported by biochemical parameters, by inhibiting the Acetylcholinestrase (p < 0.01) activity, increasing the GSH (p < 0.001) level and decreasing the TBARS (p < 0.001) level of whole brain. Moreover TAPH has shown the significant Monoamine oxidase-A (MAO-A) inhibition action (p < 0.001), hence it reduces the metabolism of epinephrine, 5-HT and other monoamines and enhances the action of these neurotransmitters indirectly; this adrenergic system plays an important role in learning and memory. Further, TAPH (5 mg kg(-1)) protect the DNA fragmentation of frontotemporal cortex of the brain from hypoxic effect induced by Sodium nitrite in Gel Electrophoresis studies. The results were comparable to their respective standards. Hence, harmine alkaloids are potential enough to utilize in the management of Neurodegenerative disorders of the type Alzheimer's diseases. PMID:24506035

Biradar, S M; Joshi, Hanumanthachar; Tarak, K C

2013-12-01

284

Hepatitis C  

MedlinePLUS Videos and Cool Tools

... to prevent Hepatitis C are: 1. Practice safe sex by using condoms, and knowing your partner. 2. ... that risk. Such practices include for example “rough” sex and anal sex. This document is for informational ...

285

[Hepatic granulomatosis].  

PubMed

Granulomatous hepatitis is not a uniform disease entity but a generic histopathologic diagnosis. The present review of aetiology and epidemiology of granulomas in the liver, shows that in the past tuberculosis and sarcoidosis were the most frequent but there remained a large percentage of "undiagnosis" cases; at the present drug-induced granulomatous hepatitis are frequently reported and "undiagnosed cases" are rare. Analysis of the hystological features of the most common granulomas is presented. PMID:6687632

Marcarino, C; Calcamuggi, G; Musorrofiti, A

1983-03-17

286

Mistletoe Hepatitis  

Microsoft Academic Search

A 49-year-old woman presented with nausea, general malaise, and a dull ache in the right hypochondrium. Liver biopsy showed slight inflammatory-cell infiltration, and results of liver function tests suggested hepatitis. Hepatitis B surface antigen was not detected, and a cholecystogram was normal. Two years later she presented with similar symptoms, and both illnesses were found to have occurred after ingestion

John Harvey; D. G. Colin-Jones

1981-01-01

287

Delta agent (Hepatitis D)  

MedlinePLUS

Hepatitis D virus ... Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make a ... B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs ...

288

Hepatitis-Associated Antigen Hepatitis  

PubMed Central

Light and electron microscopic examinations were carried out on liver tissues from 6 renal transplant recipients who developed Australia antigen-associated hepatitis, referred to in this paper as hepatitis-associated antigen (HAA) hepatitis. While under immunosuppressive therapy, the patients showed rapid progression of acute hepatitis to chronic active hepatitis and posthepatitic cirrhosis resulting in liver failure. By electron microscopy, in 5 of 6 patients, characteristic virus-like particles of 230 Ĺ size were observed in massive numbers in the nucleus and occasionally in the cytoplasm of liver cells. No similar particles were found in liver biopsies from other patients. These particles had an appearance of nucleocapsid without an outer coat, and were believed to be the viruses in their natural infective states. The predominantly intranuclear location of the particles and the associated nuclear changes suggested that the nucleus is the primary site of virus replication. The finding of the virus-like particles is believed to be diagnostic for HAA hepatitis. While HAA is implicated in serum hepatitis, the identification of HAA with the virus-like particles of this study is still to be established. In the phagosomes, there were some particles showing an outer membrane and a tail-like structure. Both the coated and the noncoated particles were believed to be the same virus. The phagosomes also contained what appeared to be “degradated” viral material. The lysosomal activity in the infected hepatitic cells seemed to be increased. This study showed nonspecific changes of the liver cell nuclei and organelles, probably related to viral infection. The precise mechanism of cell injury remains to be elucidated. However, the result of this study has provided a reasonable basis for future investigations of HAA hepatitis. ImagesFig 10Fig 1Fig 2Fig 3Fig 4Fig 6Fig 7Fig 8Fig 9Fig 12Fig 5Fig 11Fig 13

Huang, Shao-nan

1971-01-01

289

Hepatitis B Frequently Asked Questions  

MedlinePLUS

... to... Ańadir en... Favorites Delicious Digg Google Bookmarks Hepatitis B FAQs for the Public Index of Questions ± Overview ... C. What is the difference between Hepatitis A, Hepatitis B, and Hepatitis C? Hepatitis A , Hepatitis B , and ...

290

Acute liver damage and ecstasy ingestion  

Microsoft Academic Search

Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted

A J Ellis; J A Wendon; B Portmann; R Williams

1996-01-01

291

Mistletoe hepatitis.  

PubMed Central

A 49-year-old woman presented with nausea, general malaise, and a dull ache in the right hypochondrium. Liver biopsy showed slight inflammatory-cell infiltration, and results of liver function tests suggested hepatitis. Hepatitis B surface antigen was not detected, and a cholecystogram was normal. Two years later she presented with similar symptoms, and both illnesses were found to have occurred after ingestion of a herbal remedy containing kelp, motherwort, skullcap, and mistletoe. A challenge test established this to be the cause of the illness. Mistletoe is the only constituent of the tablets known to contain any potential toxin and thus was probably the cause of the illness. Mistletoe is widely used in herbal remedies, whose ingestion may therefore cause hepatitis. Images FIG 1 FIG 2

Harvey, J; Colin-Jones, D G

1981-01-01

292

Hepatitis C and pregnancy  

PubMed Central

Acute hepatitis C is a rare event in pregnancy. The most common scenario is chronic hepatitis C virus (HCV) infection in pregnancy. During pregnancy in women with chronic HCV infection a significant reduction in mean alanine aminotransferase levels has been reported, with a rebound during the postpartum period. In few cases exacerbation of chronic hepatitis C has been reported in pregnancy. A cofactor that might play a role in the reduction of liver damage is the release of endogenous interferon from the placenta. Observations regarding serum HCV-RNA concentration have been variable. In some women HCV-RNA levels rise toward the end of pregnancy. In general, pregnancy does not have a negative effect on HCV infection. Conversely, chronic hepatitis does not appear to have an adverse effect on the course of pregnancy, or the birth weight of the newborn infant. The role of spontaneous abortion is approximately the same as in the general population. The overall rate of mother-to-child transmission for HCV is 3%-5% if the mother is known to be anti-HCV positive. Co-infection with human immunodeficiency virus (HIV) increases the rate of mother-to-child transmission up to 19.4%. Numerous risk factors for vertical transmission have been studied. In general, high viral load defined as at least 2.5 × 106 viral RNA copies/mL, HIV co-infection, and invasive procedures are the most important factors. Both interferon and ribavirin are contraindicated during pregnancy. Viral clearance prior to pregnancy increases the likelihood that a woman remains non-viremic in pregnancy with a consequent reduced risk of vertical transmission.

Floreani, Annarosa

2013-01-01

293

Hepatic vein obstruction in idiopathic hypereosinophilic syndrome.  

PubMed

We report an association between idiopathic hypereosinophilic syndrome and obstruction of the hepatic veins (Budd-Chiari syndrome). Budd-Chiari syndrome was assessed by liver biopsy and hepatic phlebography and documented by computed tomography. Postmortem examination revealed fibrous occlusion of the hepatic venous tree, as well as fibrosis of the endocardium and of myocardial and pulmonary vessels. To our knowledge, the association between idiopathic hypereosinophilic syndrome and Budd-Chiari syndrome has never previously been reported. Since it has been suggested that hypereosinophilia might cause endothelium damage, a link between these two entities is postulated. PMID:3985740

Elouaer-Blanc, L; Zafrani, E S; Farcet, J P; Saint-Marc Girardin, M F; Mathieu, D; Dhumeaux, D

1985-04-01

294

Neonatale Hepatitis  

Microsoft Academic Search

During the period 1961–1966 12 children (6 males, 6 females) underwent thorough clinical investigations because of neonatal hepatitis. The onset of jaundice varied from the first day of life to the third month; jaundice lasted from between 30 to 150 days. Laboratory tests — including the determination of several serum enzyme activities — did not make possible a definite differentiation

Wulff-Dietrich Beseler; Hans Werner Rotthauwe

1971-01-01

295

Hepatitis C: progress and problems.  

PubMed Central

The hepatitis C virus (HCV), a single-stranded RNA virus, is the major cause of posttransfusion hepatitis. HCV isolates differ in nucleotide and amino acid sequences. Nucleotide changes are concentrated in hypervariable regions and may be related to immune selection. In most immunocompetent persons, HCV infection is diagnosed serologically, using antigens from conserved regions. Amplification of RNA may be necessary to detect infection in immunosuppressed patients. Transmission by known parenteral routes is frequent; other means of spread are less common and may represent inapparent, percutaneous dissemination. Infection can lead to classical acute hepatitis, but most infected persons have no history of acute disease. Once infected, most individuals apparently remain carriers of the virus, with varying degrees of hepatocyte damage and fibrosis ensuing. Chronic hepatitis may lead to cirrhosis and hepatocellular carcinoma. However, disease progression varies widely, from less than 2 years to cirrhosis in some patients to more than 30 years with only chronic hepatitis in others. Determinants important in deciding outcome are unknown. Alpha interferon, which results in sustained remission in selected patients, is the only available therapy. Long-term benefits from such therapy have not been demonstrated. Prevention of HCV infection by vaccination is likely to be challenging if ongoing viral mutation results in escape from neutralization and clearance.

Cuthbert, J A

1994-01-01

296

Quantitative evaluation of rabbit's hepatic function by HEF, DISADA-K, and ICG Rmax methods  

Microsoft Academic Search

The hepatic extraction fraction (HEF), DISIDA-K, and ICG Rmax were obtained to evaluate hepatic function for two normal and four abnormal rabbits with rapidly damaged livers. The correlation coefficients among these three methods were found. The correlation coefficient between the HEF and ICG Rmax which is a standard technique in evaluating hepatic function was found to be 0.93. Therefore the

D. W. Kim; S. C. Kim; S. J. Yoon; J. D. Lee; B. R. Kim

1996-01-01

297

Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis  

PubMed Central

This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracellular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers.

Osna, Natalia A; Thomes, Paul G; Jr, Terrence M Donohue

2011-01-01

298

Diclofenac hepatitis  

Microsoft Academic Search

The characteristics of liver damage associated with the use of diclofenac, a popular nonsteroidal anti-inflammatory drug, were investigated by reviewing adverse drug reaction reports for Australia. Twenty six patients were reported for whom diclofenac was the sole suspected drug cause of their liver damage. The average age of the patients was 64 years (range 37-84 years); 19 (70%) were women.

P Purcell; D Henry; G Melville

1991-01-01

299

What Is Hepatitis?  

MedlinePLUS

... and effective vaccines are available to prevent HAV. Hepatitis B virus (HBV) is transmitted through exposure to infective ... serious disease and worse outcome. Safe and effective hepatitis B vaccines provide protection from HDV infection. Hepatitis E ...

300

Hepatitis B virus (image)  

MedlinePLUS

Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

301

Diabetes and Hepatitis B Vaccination  

MedlinePLUS

Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results ... as liver failure or liver cancer. How is hepatitis B spread? The hepatitis B virus is usually spread ...

302

[Hepatic fascioliasis].  

PubMed

Hepatic fascioliasis is a pathology with an increasing incidence, morbidity and mortality all over the world and most particularly in our country, where endemic spots have been found, particularly in rural areas. Based on a clinical case which is supported by a revision of appropriate literature, the authors have made relevant considerations on bio-ecology, diagnosis, prognostic and treatment of this disease. PMID:9235854

Tavares, C; Freitas, P; Afonso, C

1997-01-01

303

Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis  

Microsoft Academic Search

Background\\/Aims: Little is known about the pathogenesis of liver damage related to hepatitis C virus. The presence of steatosis or increased ferritin levels, and preliminary data on the relevance of iron as a prognostic factor prompted us to ascertain whether hepatitis C virus-related liver damage might be mediated by iron accumulation.Methods: We evaluated the degree of hepatic inflammation and steatosis,

Fabio Farinati; Romilda Cardin; Nicola De Maria; Gianni Della Libera; Cinzia Marafin; Enrico Lecis; Patrizia Burra; Annarosa Floreani; Attilio Cecchetto; Remo Naccarato

1995-01-01

304

Tornado Damage!  

NSDL National Science Digital Library

Students learn about tornadoes, the damage they cause, and how to rate tornadoes. Specifically, students investigate the Enhanced Fujita Damage Scale of tornado intensity, and use it to complete a mock engineering analysis of damage caused by a tornado. Additional consideration is given to tornado warning systems and how these systems can be improved to be safer. Lastly, students learn basic tornado safety procedures.

Integrated Teaching And Learning Program

305

Autophagy by hepatitis B virus and for hepatitis B virus.  

PubMed

Autophagy is a catabolic process by which cells remove unwanted proteins and damaged organelles. It is important for maintaining cellular homeostasis and can also be used by cells to remove intracellular microbial pathogens. As such, some viruses such as herpes simplex virus-1 (HSV-1) have evolved mechanisms to suppress autophagy for their survival. In contrast, other viruses such as poliovirus, hepatitis C virus (HCV) and dengue viruses have instead evolved mechanisms to use this pathway to enhance their replication. Recently, we demonstrated that hepatitis B virus (HBV), a DNA virus that infects hepatocytes, could enhance and use autophagy for its DNA replication. This enhancement of autophagy is mediated by its X protein, which binds to and activates phosphatidylinositol-3-kinase class 3 (PI3KC3), an enzyme important for the initiation of autophagy. The persistent activation of autophagy in hepatocytes by HBV during chronic infection may play an important role in HBV pathogenesis. PMID:20305390

Sir, Donna; Ann, David K; Ou, Jing-Hsiung James

2010-05-01

306

Hepatitis B therapy  

Microsoft Academic Search

The goal of hepatitis B treatment is to prevent cirrhosis, liver decompensation and hepatocellular carcinoma. In clinical practice, treatment response is determined by suppression of serum HBV DNA levels, hepatitis B e antigen seroconversion to hepatitis B e antibody, hepatitis B surface antigen loss, normalization of alanine aminotransferase levels and improvement in liver histology. Patients with life-threatening liver disease, and

Hellan Kwon; Anna S. Lok

2011-01-01

307

Therapy of Viral Hepatitis  

Microsoft Academic Search

Worldwide viral hepatitis is the most common cause of jaundice, chronic liver disease cirrhosis and hepatocellular carcinoma. While important advances have been made in prevention of viral hepatitis, therapy of this disease remains unsatisfactory. There are no specific therapies of proven benefit for acute hepatitis, although use of alpha-interferon during the acute phase of hepatitis C may result in a

Jay H. Hoofnagle

1998-01-01

308

Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity  

PubMed Central

Background Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids, terpenylated dihydrochalcones and benzoic acids and has been reported to possess anti-inflammatory activity. The purpose of this study is to assess the gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive compound from M. kentii, on gastric ulcer models in rats. Methods DES was isolated from the bark of M. kentii. Experimental rats were orally pretreated with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content, gastric acidity and histological gastric lesions were assessed in vivo. The effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH) content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2-associated X (Bax) protein expression and Helicabacter pylori (H pylori) were also investigated. Results DES pre-treatment at the administered doses significantly attenuated ethanol-induced gastric ulcer; this was observed by decreased gastric ulcer area, reduced or absence of edema and leucocytes infiltration compared to the ulcer control group. It was found that DES maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level, increased NP-SH content and NO level and inhibited COX-2 activity. The compound up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein expression in the ulcerated tissue. DES showed interesting anti-H pylori effects. The efficacy of DES was accomplished safely without any signs of toxicity. Conclusions The current study reveals that DES demonstrated gastroprotective effects which could be attributed to its antioxidant effect, activation of HSP-70 protein, intervention with COX-2 inflammatory pathway and potent anti H pylori effect.

2013-01-01

309

Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities  

PubMed Central

1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. `Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis.

Savolainen, Markku J.; Hiltunen, J. Kalervo; Hassinen, Ilmo E.

1977-01-01

310

[Toxic hepatitis induced by Polygonum multiflorum].  

PubMed

Toxic liver injury is a common cause of acute hepatitis. Here we report a case of 33-year old female with toxic hepatitis caused by unusual agent- extract of chinese plant Polygonum multiflorum. The patient presented with clinical signs of nausea and icterus and laboratory signs of hepatocellular damage following 2 months of readministration of Polygonum mulltiflorum pills. All other causes of hepatocellular damage were excluded. The causality between hepatocellular damage and Polygonum multiflorum ingestion was supported by early recovery after discontinuation, by international scoring system of causality between drug and hepatotoxicity as well as by similarities with other reports from the literature. Considering the growing popularity of herbal products as nutrition supplements we appeal to caution in using these preparations. PMID:23691566

Banarova, A; Koller, T; Payer, J

2012-12-01

311

Hepatic hydrothorax.  

PubMed

Hepatic hydrothorax is defined as a pleural effusion in patients with liver cirrhosis in the absence of cardiopulmonary disease. The estimated prevalence among patients with liver cirrhosis is approximately 5-6%. The pathophysiology involves the passage of ascitic fluid from the peritoneal cavity to the pleural space through diaphragmatic defects. The diagnosis is made from clinical presentation and confirmed by diagnostic thoracentesis with pleural fluid analysis. The initial medical management is sodium restriction and diuretics, but liver transplantation provides the only definitive therapy. For patients who are not transplant candidates and those who await organ availability, other therapeutic modalities that are to be considered include transjugular intrahepatic portosystemic shunt placement, videoassisted thoracoscopic surgery repair, pleurodesis, and vasoconstrictors (eg, octreotide and terlipressin). The primary therapeutic goals are to reduce ascitic fluid production and improve symptoms to bridge the time for liver transplantation. PMID:23085762

Baikati, Kiran; Le, Duong L; Jabbour, Ibrahim I; Singhal, Shashideep; Anand, Sury

2014-01-01

312

Hepatitis B  

Microsoft Academic Search

Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a The management of acute HBV infection is supportive.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Specific treatment is not indicated for HBV carriers because they often have no evidence of liver injury, and, further, do\\u000a not respond to currently available therapies.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Interferon monotherapy is best indicated for patients with chronic replicating HBV infection and evidence of chronic hepatitis.\\u000a There is an increased

Tiffany Weakley; K. Rajender Reddy

1999-01-01

313

Impaired plasma lipid profiles in acute hepatitis  

PubMed Central

The present study examined plasma lipid profiles in thirty patients suffered from acute viral hepatitis. Patients' blood samples were collected at both the debut and recovery of diseases. Thirty sex and age matched normal subjects were included as controls. Plasma total triglycerides (TG), total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), lipoprotein (a) (Lp(a)), blood coagulation status including prothrombin complex activity and activated partial tromboplastin time (APTT), and hepatic functions were determined by the automatic biochemical analytical instrument. It demonstrated that plasma levels of total cholesterol, HDL-C and apoAI were significantly lower in the patients at the acute phase of hepatitis than those in normal subjects, whereas plasma levels of TG and LDL-C were obviously higher in the patients than in normal subjects (P < 0.05). Moreover, we demonstrated that patients' plasma levels of total cholesterol, LDL-C, HDL-C and apoAI were lower at the active phase of the diseases than at the recovering phase, which indicating that acute liver damage could significant influence lipid metabolism in vivo. No pathological changes of blood coagulation status occurred in these patients during the study as all selected patients had moderate hepatitis. It may conclude that examinations of plasma lipid profile could be considered as a clinical index to reflect liver damage in the active phase of hepatitis.

2010-01-01

314

Hepatitis D Co-Infection  

MedlinePLUS

... News Calendar of Events Personal Stories HBF Annual Report What is Hepatitis B? ABC's of Viral Hepatitis About Hepatitis B Hepatitis B Co-Infection Your Liver & Its Functions Donating Blood Glossary ...

315

Effect of cimetidine and ranitidine on drug induced damage to gastric epithelial cell monolayers in vitro.  

PubMed Central

The effect of the H2 blockers cimetidine and ranitidine on drug induced damage to gastric cell monolayers has been evaluated in conditions independent of systemic factors and their anti-acid properties. Monolayers of mucous cells from a human cell line MKN 28, obtained from a human gastric adenocarcinoma, have been studied. Cell damage has been assessed qualitatively by trypan blue dye exclusion test and quantitatively by 51Cr release assay. Cimetidine and ranitidine significantly protected cultured cells against damage induced by sodium taurocholate decreasing taurocholate induced 51Cr release by 36% (p less than 0.001) and 28% (p less than 0.01), respectively. Cimetidine was also protective in concentrations lower than ranitidine. This protection was not prevented by the prostaglandin synthesis inhibitor indomethacin nor by the sulph-hydryl blocker N-ethylmaleimide. Incubation with cimetidine and ranitidine did not increase the production of PGE2 by cultured cells nor did it affect the cellular level of sulph-hydryl compounds. Cimetidine and ranitidine did not afford protection against damage induced by indomethacin and ethanol. Cimetidine in a concentration of 10 4M increased ethanol induced damage significantly. In conclusion (1) cimetidine and ranitidine protect gastric cells against taurocholate induced damage in vitro, independently of their anti-acid effect; (2) this protection is not mediated by prostaglandin E2 or sulph-hydryl compounds; (3) cimetidine and ranitidine do not protect gastric cells against damage induced by indomethacin and ethanol. Images Fig. 1

Romano, M; Razandi, M; Ivey, K J

1989-01-01

316

Hepatic wound repair  

PubMed Central

Background Human chronic liver diseases (CLDs) with different aetiologies rely on chronic activation of wound healing that represents the driving force for fibrogenesis progression (throughout defined patterns of fibrosis) to the end stage of cirrhosis and liver failure. Issues Fibrogenesis progression has a major worldwide clinical impact due to the high number of patients affected by CLDs, increasing mortality rate, incidence of hepatocellular carcinoma and shortage of organ donors for liver transplantation. Basic science advances Liver fibrogenesis is sustained by a heterogeneous population of profibrogenic hepatic myofibroblasts (MFs), the majority being positive for ? smooth muscle actin (?SMA), that may originate from hepatic stellate cells and portal fibroblasts following a process of activation or from bone marrow-derived cells recruited to damaged liver and, in a method still disputed, by a process of epithelial to mesenchymal transition (EMT) involving cholangiocytes and hepatocytes. Recent experimental and clinical data have identified, at tissue, cellular and molecular level major profibrogenic mechanisms: (a) chronic activation of the wound-healing reaction, (b) oxidative stress and related reactive intermediates, and (c) derangement of epithelial-mesenchymal interactions. Clinical care relevance Liver fibrosis may regress following specific therapeutic interventions able to downstage or, at least, stabilise fibrosis. In cirrhotic patients, this would lead to a reduction of portal hypertension and of the consequent clinical complications and to an overall improvement of liver function, thus extending the complication-free patient survival time and reducing the need for liver transplantation. Conclusion Emerging mechanisms and concepts related to liver fibrogenesis may significantly contribute to clinical management of patients affected by CLDs.

Parola, Maurizio; Pinzani, Massimo

2009-01-01

317

Hepatitis (For Parents)  

MedlinePLUS

... adults. Most are not approved for use in children but some are used in select circumstances. Not all patients with hepatitis B require medication. The treatment of chronic hepatitis C has improved significantly with the use ...

318

Hepatitis C (image)  

MedlinePLUS

Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs ...

319

Hepatitis B Test  

MedlinePLUS

... IgM; anti-HBe; Hepatitis B e Antibody; HBV DNA Formal name: Hepatitis B Virus Testing Related tests: ... of tests detect or evaluate the genetic material ( DNA ) of the virus. The pattern of test results ...

320

Hepatitis C and Incarceration  

MedlinePLUS

... Hepatitis C from one person to another. Tattoos/Piercing/Scarring: Sex: The Hepatitis C virus can be ... can be spread when tattoo, body art, or piercing equipment has tiny amounts of blood on it. ...

321

Hepatitis B Foundation  

MedlinePLUS

... Other Helpful Links Welcome to the Hepatitis B Foundation Top Stories HBV Therapy May Cut Liver Cancer ... national coalition co-chaired by the Hepatitis B Foundation and the Association of Asian Pacific Community Health ...

322

Viral Hepatitis Therapies  

MedlinePLUS

... brand name for additional information. Approved Treatments for Hepatitis B Brand Name Generic Names Manufacturer Name Indication Baraclude entecavir Bristol-Myers Squibb chronic hepatitis B virus infection with evidence of active viral replication ...

323

Hepatitis B Vaccination Protection  

MedlinePLUS

... of those vaccinated will develop immunity to the hepatitis B virus. The vaccine causes no harm to those ... vaccination. This written opinion is limited to whether hepatitis B vaccination is indicated for the worker and if ...

324

Hepatitis B Symptoms  

MedlinePLUS

... JavaScript on. Read more information on enabling JavaScript. Hepatitis B Skip Content Marketing Share this: Main Content Area Symptoms Hepatitis B does not always cause obvious symptoms. Children are ...

325

Prevention of viral hepatitis  

Microsoft Academic Search

Opinion statement  Despite the availability of vaccines against hepatitis A and B, acute viral hepatitis due to these agents continues to be\\u000a among the most commonly reported notifiable infectious diseases in the United States. Currently available hepatitis A and\\u000a B vaccines are highly immunogenic and well tolerated, but vaccine coverage needs to be expanded. Use of the hepatitis A vaccine\\u000a in

Raymond S. Koff

2002-01-01

326

Right Hemisphere Brain Damage  

MedlinePLUS

Right Hemisphere Brain Damage [ en Espańol ] What is right hemisphere brain damage ? What are some signs or symptoms of right hemisphere ... right hemisphere brain damage ? What is right hemisphere brain damage? Right hemisphere brain damage is damage to ...

327

Diclofenac induced hepatitis  

Microsoft Academic Search

Summary Diclofenac is a frequently prescribed nonsteroidal antiinflammatory drug (NSAID). Significant hepatotoxicity related to diclofenac may be more common than previously recognized, as three patients with diclofenac-associated hepatitis were seen by one clinician in a single year. All patients were ANA positive during the hepatitis and had histologic features of chronic active hepatitis. Two had been inappropriately treated with corticosteroids.

L. J. Scully; D. Clarke; R. J. Barr

1993-01-01

328

Treatment of hepatitis C  

Microsoft Academic Search

Hepatitis C virus is a leading cause of chronic liver disease, with over 170 million people infected worldwide. It is also the leading indication for liver transplantation. Complications from chronic hepatitis C infection include cirrhosis, hepatic decompensation, and hepatocellular carcinoma. As a result, treatment strategies to prevent such complications have been widely researched, although many questions remain unanswered. To date,

Andrew I. Kim; Sammy Saab

2005-01-01

329

Management of hepatic coma complicating viral hepatitis  

Microsoft Academic Search

The treatment is described of 17 patients with presumed viral hepatitis who developed hepatic coma unresponsive to standard conservative measures. Five patients were considered for treatment by exchange transfusion. Four were treated, with transient improvement in two, but all died. Nine patients were considered for treatment by heterologous liver perfusion. Six were treated, with transient improvement in two and complete

R. C. Pirola; J. M. Ham; R. G. Elmslie

1969-01-01

330

Ammonia: Key factor in the pathogenesis of hepatic encephalopathy  

Microsoft Academic Search

There is substantial clinical and experimental evidence to suggest that ammonia toxicity is a major factor in the pathogenesis\\u000a of hepatic encephalopathy associated with subacute and chronic liver disease. Ammonia levels in patients with severe liver\\u000a disease are frequently found to be elevated both in blood and cerebrospinal fluid (csf). Hepatic encephalopathy results in\\u000a neuropathological damage of a similar nature

Roger F. Butterworth; Jean-François Gigučre; Jean Michaud; Joël Lavoie; Gilles Pomier Layrargues

1987-01-01

331

Nimesulide-induced acute hepatitis: evidence from six cases  

Microsoft Academic Search

Background\\/Aims: A number of nonsteroidal anti-inflammatory drugs have been reported to provoke hepatic injury. Nimesulide is a new agent of the sulfonanilide class, and is a more selective inhibitor of cyclooxygenase type 2 than of type 1. Well-documented cases of acute hepatitis have not yet been reported with this drug. We report on six patients who developed acute liver damage

Werner Van Steenbergen; Pascal Peeters; Joris De Bondt; Dirk Staessen; Henri Büscher; Thiery Laporta; Tania Roskams; Valeer Desmet

1998-01-01

332

How Can We Make Decision for Patients With Chronic Hepatitis B According to Hepatitis B Virus (HBV) DNA Level?  

PubMed Central

Background: HBeAg negative hepatitis B infection exerts both inactive carrier state and chronic active hepatitis, which are sometimes difficult to differentiate. Serial hepatitis B virus (HBV) DNA quantification, alanine transaminase (ALT) measurement, and liver histology assessment can help to differentiate these forms of hepatitis B infection. Objectives: We aimed to clarify the clinical and laboratory characteristics of HBeAg negative hepatitis B patients. Patients and Methods: Patients with hepatitis B, referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2013, were included and followed for one year. Laboratory assessments including liver function tests, HBV DNA quantification, and liver biopsy (for some cases) were performed. Results: Two hundred forty-three HBeAg negative hepatitis B patients were stratified into three groups based on to their HBV DNA level including group 1 (G1) with HBV DNA level < 2000 IU/mL, group 2 (G2) with HBV DNA level 2000-20000 IU/mL, and group 3 (G3) with HBV DNA level > 20000 IU/mL. The G2 had more similarity to G1 than G3 regarding their clinical characteristics. Conclusions: It is concluded that most HBeAg negative hepatitis B patients with serum HBV DNA level of 2000-20000 IU/mL, persistent normal ALT concentration, and no or mild liver damage on biopsy can be clinically managed as HBV inactive carriers.

Keshvari, Maryam; Alavian, Seyed Moayed; Sharafi, Heidar

2014-01-01

333

Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis.  

PubMed

Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c+ I-A(low) B220+); however, conventional DC were CD11c+ I-A(high) B220(-). At an early stage (3-6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12-24?h) in parallel with hepatic failure. The hepatic CD11c+ DC population contained many CD11b(-) cells, while the majority of splenic CD11c+ DC were CD11b+. After Con A administration, the proportion of I-A+ and CD11b+ cells within the CD11c+ DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c+ DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function. PMID:21985372

Tomiyama, C; Watanabe, H; Izutsu, Y; Watanabe, M; Abo, T

2011-11-01

334

Pathogenesis of Hepatic Encephalopathy  

PubMed Central

Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

Ciecko-Michalska, Irena; Szczepanek, Malgorzata; Slowik, Agnieszka; Mach, Tomasz

2012-01-01

335

Reversed light-dark cycle and cage enrichment effects on ethanol-induced deficits in motor coordination assessed in inbred mouse strains with a compact battery of refined tests  

PubMed Central

The laboratory environment existing outside the test situation itself can have a substantial influence on results of some behavioral tests with mice, and the extent of these influences sometimes depends on genotype. For alcohol research, the principal issue is whether genotype-related ethanol effects will themselves be altered by common variations in the lab environment or instead will be essentially the same across a wide range of lab environments. Data from 20 inbred strains were used to reduce an original battery of seven tests of alcohol intoxication to a compact battery of four tests: the balance beam and grip strength with a 1.25 g/kg ethanol dose and the accelerating rotarod and open-field activation tests with 1.75 g/kg. The abbreviated battery was then used to study eight inbred strains housed under a normal or reversed light-dark cycle, or a standard or enriched home cage environment. The light-dark cycle had no discernable effects on any measure of behavior or response to alcohol. Cage enrichment markedly improved motor coordination in most strains. Ethanol-induced motor coordination deficits were robust; the well documented strain-dependent effects of ethanol were not altered by cage enrichment.

Munn, Elizabeth; Bunning, Mark; Prada, Sofia; Bohlen, Martin; Crabbe, John C.; Wahlsten, Douglas

2011-01-01

336

Sexually acquired hepatitis  

PubMed Central

Objectives: To assess current knowledge of sexually transmitted viral hepatitis in relation to epidemiology, clinical presentation, management, and diagnosis with particular reference to resource-poor settings. Method: A search of published literature identified through Medline from 1966 to October 2001, the Cochrane Library, and reference lists taken from each article obtained. Textword and MeSH searches for hepatitis A, B, C, D, E, G, delta, GB virus, GBV-C, and TT virus were linked to searches under the textword terms sex$, prevent$, and MeSH subheadings, microbiology, complications, drug therapy, therapy, diagnosis, epidemiology, transmission, and prevention and control. Conclusions: In heterosexual relationships, hepatitis B is readily transmitted sexually and hepatitis C and D less so, with no evidence for sexual transmission of hepatitis A. Hepatitis types A‘D are all transmissible sexually in male homosexual relationships under certain conditions. In resource-poor countries sexual transmission is generally only a significant route of transmission for hepatitis B.

Brook, M

2002-01-01

337

Administration of memantine during ethanol withdrawal in neonatal rats: effects on long-term ethanol-induced motor incoordination and cerebellar Purkinje cell loss  

PubMed Central

Background Alcohol consumption during pregnancy can damage the developing fetus, illustrated by central nervous system dysfunction and deficits in motor and cognitive abilities. Binge drinking has been associated with an increased risk of fetal alcohol spectrum disorders, likely due to increased episodes of ethanol withdrawal. We hypothesized that overactivity of the N-methyl-D-aspartate (NMDA) receptor during ethanol withdrawal leads to excitotoxic cell death in the developing brain. Consistent with this, administration of NMDA receptor antagonists (e.g. MK-801) during withdrawal can attenuate ethanol's teratogenic effects. The aim of this study was to determine if administration of memantine, an NMDA receptor antagonist, during ethanol withdrawal could effectively attenuate ethanol-related deficits, without the adverse side effects associated with other NMDA receptor antagonists. Methods Sprague-Dawley pups were exposed to 6.0 g/kg ethanol or isocaloric maltose solution via intubation on postnatal day 6, a period of brain development equivalent to a portion of the 3rd trimester. Twenty-four and 36 hours after ethanol, subjects were injected with 0, 10 or 15 mg/kg memantine, totaling doses of 0, 20, or 30 mg/kg. Motor coordination was tested on a parallel bar task and the total number of cerebellar Purkinje cells was estimated using unbiased stereology. Results Alcohol exposure induced significant parallel bar motor incoordination and reduced Purkinje cell number. Memantine administration significantly attenuated both ethanol-associated motor deficits and cerebellar cell loss in a dose-dependent manner. Conclusions Memantine was neuroprotective when administered during ethanol withdrawal. These data provide further support that ethanol withdrawal contributes to fetal alcohol spectrum disorders.

Idrus, Nirelia M.; McGough, Nancy N.H.; Riley, Edward P.; Thomas, Jennifer D.

2013-01-01

338

Fulminant hepatic failure in nephrotic syndrome related to withdrawal of immunosuppressive therapy.  

PubMed Central

Two patients with nephrotic syndrome developed fatal fulminant hepatitis B following withdrawal of prednisolone or cyclophosphamide. Immunosuppressive therapy probably enhanced hepatitis B virus (HBV) replication and widespread infection of hepatocytes; its withdrawal permitted a return of immune competence resulting in massive destruction of infected hepatocytes. Prior screening of all patients for hepatitis B surface antigen, gradual withdrawal of immunosuppressive drugs with careful monitoring, and prompt intervention with corticosteroids at the first clinical or biochemical signs of liver cell damage may prevent this complication.

Onwubalili, J. K.

1988-01-01

339

Role of viral factors in the natural course and therapy of chronic hepatitis B  

Microsoft Academic Search

Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute\\u000a or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis\\u000a of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host\\u000a interactions, the natural history of HBV

Jia-Horng Kao

2007-01-01

340

Helenalin attenuates alcohol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and suppressing HSC activation.  

PubMed

A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen ? type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-?1, TNF-?, IL-6 and IL-1? and myeloperoxidase, via down-regulation of NF-?B. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-?, platelet-derived growth factor-? and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of ?-SMA and TGF-? levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima. PMID:24704336

Lin, Xing; Zhang, Shijun; Huang, Renbin; Wei, Ling; Tan, Shimei; Liang, Shuang; Tian, Yuanchun; Wu, Xiaoyan; Lu, Zhongpeng; Huang, Quanfang

2014-06-01

341

Neuronal cell death in hepatic encephalopathy  

Microsoft Academic Search

It is generally assumed that neuronal cell death is minimal in liver failure and is insufficient to account for the neuropsychiatric\\u000a symptoms characteristic of hepatic encephalopathy. However, contrary to this assumption, neuronal cell damage and death are\\u000a well documented in liver failure patients, taking the form of several distinct clinical entities namely acquired (non-Wilsonian)\\u000a hepatocerebral degeneration, cirrhosis-related Parkinsonism, post-shunt myelopathy

Roger F. Butterworth

2007-01-01

342

Hepatic Microcirculatory Changes in Acute and Chronic Carbon Tetrachloride Poisoning in Rats.  

National Technical Information Service (NTIS)

A study of the hepatic microvasculature was carried out in the course of prolonged carbon tetrachloride poisoning, utilizing a silicone rubber perfusion technique. Consistent and rather selective damage was confined to central veins and centrilobular sinu...

T. Hase

1966-01-01

343

Cytotoxic effects of a leukocidin from Fusobacterium necrophorum on bovine hepatic cells  

Microsoft Academic Search

Cytotoxic effects of a leukocidin from Fusobacterium necrophorum were demonstrated on bovine hepatic cells. The cytotoxic response was dose-dependent and could be inhibited by homologous antiserum. Scanning electron microscopy revealed damaged hepatic cell surface. These findings indicated a pathogenic role of the leukocidin in F. necrophorum infections.

T. Ishii; M. Kanoe; T. Inoue; K. Kai; H. Blobel

1987-01-01

344

Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes.  

PubMed

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and putatively also non-Hodgkin's B cell lymphoma. In this study, we demonstrated that PBMCs obtained from HCV-infected patients showed frequent chromosomal aberrations and that HCV infection of B cells in vitro induced enhanced chromosomal breaks and sister chromatid exchanges. HCV infection hypersensitized cells to ionizing radiation and bleomycin and inhibited nonhomologous end-joining repair. The viral core and nonstructural protein 3 proteins were shown to be responsible for the inhibition of DNA repair, mediated by NO and reactive oxygen species. Stable expression of core protein induced frequent chromosome translocations in cultured cells and in transgenic mice. HCV core protein binds to the NBS1 protein and inhibits the formation of the Mre11/NBS1/Rad50 complex, thereby affecting ATM activation and inhibiting DNA binding of repair enzymes. Taken together, these data indicate that HCV infection inhibits multiple DNA repair processes to potentiate chromosome instability in both monocytes and hepatocytes. These effects may explain the oncogenicity and immunological perturbation of HCV infection. PMID:20974981

Machida, Keigo; McNamara, George; Cheng, Kevin T-H; Huang, Jeffrey; Wang, Chun-Hsiang; Comai, Lucio; Ou, Jing-Hsiung James; Lai, Michael M C

2010-12-01

345

Hepatitis C Virus Inhibits DNA Damage-Repair through Reactive Oxygen and Nitrogen Species and by Interfering with the ATM-NBS1/Mre11/Rad50 DNA Repair Pathway in Monocytes and Hepatocytes  

PubMed Central

Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma and putatively also non-Hodgkin’s B cell lymphoma. Here we demonstrated that peripheral blood mononuclear cells (PBMCs) obtained from HCV-infected patients showed frequent chromosomal aberrations and that HCV infection of B cells in vitro induced enhanced chromosomal breaks and sister chromatid exchanges. HCV infection hypersensitized cells to ionizing radiation and bleomycin and inhibited nonhomologous end-joining repair. The viral core and NS3 proteins were shown to be responsible for the inhibition of DNA repair, mediated by nitric oxide and reactive oxygen species. Stable expression of core protein induced frequent chromosome translocations in cultured cells and in transgenic mice. HCV core protein binds to the NBS1 protein and inhibits the formation of the Mre11-NBS1-Rad50 complex and thereby affecting ATM activation and inhibiting DNA binding of repair enzymes. Taken together, these data indicate that HCV infection inhibits multiple DNA repair processes to potentiate chromosome instability in both monocytes and hepatocytes. These effects may explain the oncogenicity and immunological perturbation of HCV infection.

Machida, Keigo; McNamara, George; Cheng, Kevin T.-H.; Huang, Jeffrey; Wang, Chun-Hsiang; Comai, Lucio; Ou, Jing-Hsiung James; Lai, Michael M.C.

2011-01-01

346

Protective Effect of Essential Oil from Zingiber Officinale (Zingiberaceae) on Acute Alcohol-Induced Liver Injury in Mice  

Microsoft Academic Search

Oxidative stress and lipid abnormalities after ethanol consumption are suggested to play a key role in the development of alcoholic liver injury. We investigated the induction of oxidative damage in association with triglyceride abnormalities in hepatic concentrations mice challenged with ethanol administration. Also the protective effect of ginger essential oil (GEO) extracted with supercritical carbon dioxide against ethanol-induced liver injury

Ping Liu; Jingming Li; Liyan Ma; Shuyan Li; Yuanying Ni

2011-01-01

347

Hepatic uroporphyrinogen decarboxylase activity in porphyria cutanea tarda patients: the influence of virus C infection.  

PubMed

Porphyria cutanea tarda (PCT) is caused by a decreased activity of the hepatic enzyme uroporphyrinogen decarboxylase (URO-D). This deficiency causes overproduction, hepatic deposition, and increased excretion of uroporphyrin. Iron overload and hepatic viral infections are considered aggravating factors of the disease. Two forms of PCT have been described, as follows: a familial one with an inherited decrease of URO-D activity in all tissues and a sporadic one with a decreased activity of URO-D restricted to the liver. To assess whether the hepatic URO-D returns to normal during a remission of the disease, this activity was measured in liver biopsy samples in 24 sporadic PCT patients. The hepatic and urinary porphyrin concentrations were also measured. Viral status and histopathological findings were analyzed to assess their involvement in PCT. Six patients treated by phlebotomy to reduce hepatic iron and who were considered to be in clinical remission, characterized by a disappearance of cutaneous lesions, showed higher hepatic URO-D activities and lower hepatic porphyrin concentrations than did patients with overt PCT. The medians of these variables, however, did not achieve normal values. The hepatic URO-D activity showed a significant inverse relationship with both hepatic porphyrins and urinary uroporphyrin excretion. Hepatic URO-D activity was not reduced by hepatitis C virus (HCV) infection and liver damage. We conclude that the achievement of remission in PCT largely depends on the transient normalization of hepatic URO-D activity. A small increase in hepatic coproporphyrin in nonporphyric patients could reflect hepatic injury/iron/alcohol-induced oxidative stress oxidizing the accumulated heme precursors rather than a direct effect on hepatic URO-D enzyme. PMID:9462661

Moran, M J; Fontanellas, A; Brudieux, E; Hombrados, I; de Ledinghen, V; Couzigou, P; de Verneuil, H; De Salamanca, R E

1998-02-01

348

[Viral hepatitis--trends].  

PubMed

Viral hepatitis is a serious health problem all over the world. The aim of the study is to present the actual achievements in the therapeutically field and the general knowledge concerning the subject. Are presented the etiological agents of the acute and chronic hepatitis with the focus on hepatitis B and C, which has become a priority of WHO, with an incidence of the diseases of 360 billion/year for hepatitis B and an sub estimated level for C hepatitis. The most used drugs are presented and the therapeutical combination meant to decrease biological and virusological markers (ALAT, viral load) and to ameliorate the histological aspects of the liver. In conclusion, acute and chronic viral hepatitis represents a challenge for epidemiologists who try to stop the spread of the disease, but also for the infectious diseases specialists and gastroenterologists. PMID:20700962

Manciuc, Carmen; Dorob??, Carmen; Filip-Ciubotaru, Florina-Mihaela

2010-01-01

349

Hepatitis C: Information on Testing and Diagnosis  

MedlinePLUS

... on Testing & Diagnosis HEPATITIS C What is Hepatitis C? Hepatitis C is a serious liver disease that ... failure, and even liver cancer. How is Hepatitis C spread? Hepatitis C is spread when blood from ...

350

Viral Hepatitis: A through E and Beyond  

MedlinePLUS

... usually resolves on its own over several weeks. Hepatitis B How is hepatitis B spread? Hepatitis B is spread through contact with ... via cesarean section. Who is at risk for hepatitis B? People most likely to get hepatitis B are • ...

351

Viral Hepatitis: A through E and Beyond  

MedlinePLUS

... resolves on its own over several weeks. [ Top ] Hepatitis B How is hepatitis B spread? Hepatitis B is spread through contact with ... via cesarean section. Who is at risk for hepatitis B? People most likely to get hepatitis B are ...

352

Hepatic telangiectasia and cirrhosis.  

PubMed

In a woman with hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu disease) who died of fulminant hepatitis B, autopsy revealed cirrhosis of the liver and diffuse hepatic telangiectasia. Her daughter and grandson also suffered from the hepatic involvement of HHT. Sufficient laboratory investigations were available to exclude known causes of cirrhosis. We review the relationship between Osler-Weber-Rendu disease and liver cirrhosis or fibrosis. PMID:3356877

Deviere, J; Brohee, D; Hiden, M; Bourgeois, N

1988-02-01

353

Hepatic manifestations of celiac disease  

PubMed Central

Different hepatic and biliary tract disorders may occur with celiac disease. Some have been hypothesized to share genetic or immunopathogenetic factors, such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Other hepatic changes in celiac disease may occur with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma.

Freeman, Hugh James

2010-01-01

354

Liver Damage using Suicide Genes  

PubMed Central

Liver regeneration from the facultative hepatic stem cells, the oval cells, takes place in situations in which liver regeneration from pre-existing hepatocytes is prevented. Different models have been used to stimulate oval cell response. Many of them involve the use of carcinogenic agents with or without partial hepatectomy. In this study we show that adenovirus-mediated gene transfer of the suicide gene thymidine kinase followed by ganciclovir administration caused hepatotoxicity of variable intensity. Rats with moderate elevation in serum transaminases recovered normal liver architecture few weeks after adenovirus injection. In contrast, rats with severe liver damage exhibited a marked and persisting activation of oval cells accompanied by ductular hyperplasia. In some rats, such lesion eventually evolved to cholangiofibrosis and in one rat to cholangiocarcinoma. Deposition of fibronectin and increased number of hepatic stellate cells were found in association with oval cells and cholangiofibrotic lesions. Hepatocyte growth factor was hyperexpressed in the livers with intense oval cell response or ductular proliferation, suggesting a participation of this factor in those lesions. In summary, our data demonstrate activation of oval cell response after gene transfer of thymidine kinase followed by ganciclovir administration. These findings indicate that high doses of this therapy causes liver damage together with an impairment in hepatocellular regeneration.

Bustos, Matilde; Sangro, Bruno; Alzuguren, Pilar; Gil, Ana Gloria; Ruiz, Juan; Beraza, Naiara; Qian, Chen; Garcia-Pardo, Angeles; Prieto, Jesus

2000-01-01

355

[Hepatic artery embolization for primary hepatic carcinoma].  

PubMed

Twenty patients with primary hepatic carcinoma (PHC) treated by hepatic arterial embolization in our department from Dec. 1986 to Mar. 1987 are reported. There were 15 males and 5 females. The ages ranged from 34 to 75 years with an average of 50.7. Preoperative diagnosis and localization of the tumor were done by AFP, B-us, CT and angiography (right lobe 15 cases, left lobe 1 case, both lobes 4 cases). Celiac and superior mesenteric angiography was carried out by femoral artery approach and then highly selective hepatic catheterization was utilized for hepatic arterial embolization. Antitumor agent (5-Fu, adriamycin), iophendylate and foamy gel sponge were used for peripheral and proximal embolization. Manifestations were improved in most of the patients after embolization, such as relief of abdominal pain, improvement of appetite, decrease of tumor size. Total necrosis of the tumor was found in 2 patients who underwent surgery 1 month after embolization. The side effects of the posthepatic embolization such as, nausea, vomiting, abdominal pain and fever could be relieved by symptomatic treatment. No severe complications, such as gangrene of the gall bladder, hepatic failure, liver abscess, intestinal necrosis or pulmonary embolization were found except 3 patients who died of renal failure after the procedure. The liver dys-function returned to normal within 2 weeks. Hepatic arterial embolization provides an alternative treatment for the patients with PHC who has compensated liver function without severe systemic diseases, especially renal endocrine problems and severe portal hypertension. They should have patent portal system as proved by angiography. The authors considered that this therapeutic embolization with hepatic chemotherapy infusion is safe and effective in the management of PHC. It may increase the resectability and provide palliative means for the advanced and terminal cases. PMID:2553366

Ye, W J

1989-03-01

356

Aetiopathogenesis of autoimmune hepatitis  

PubMed Central

The histological hallmark of autoimmune hepatitis (AIH) is a dense portal mononuclear cell infiltrate that invades the surrounding parenchyma and comprises T and B lymphocytes, macrophages, and plasma cells. An unknown but powerful stimulus must be promoting the formation of this massive inflammatory cellular reaction that is likely to initiate and perpetuate liver damage. An autoimmune attack can follow different pathways to inflict damage on hepatocytes. Liver damage is likely to be orchestrated by CD4+ T lymphocytes recognizing an autoantigenic liver peptide. To trigger an autoimmune response, the peptide must be embraced by an HLA class II molecule and presented to naďve CD4+ T helper (Th0) cells by professional antigen presenting cells, with the co-stimulation of ligand-ligand fostering interaction between the two cells. Th0 cells become activated, differentiate into functional phenotypes according to the cytokines prevailing in the microenvironment and the nature of the antigen, and initiate a cascade of immune reactions determined by the cytokines produced by the activated T cells. Th1 cells, arising in the presence of the macrophage-derived interleukin (IL) -12, secrete mainly IL-2 and interferon-gamma (IFN-?), which activate macrophages, enhance expression of HLA classI(increasing liver cell vulnerability to a CD8+ T cell cytotoxic attack), and induce expression of HLA class II molecules on hepatocytes. Th2 cells, which differentiate from Th0 if the microenvironment is rich in IL-4, produce mainly IL-4, IL-10, and IL-13 which favour autoantibody production by B lymphocytes. Physiologically, Th1 and Th2 antagonize each other. Th17 cells, a recently described population, arise in the presence of transforming growth factor beta (TGF-?) and IL-6 and appear to have an important effector role in inflammation and autoimmunity. The process of autoantigen recognition is strictly controlled by regulatory mechanisms, such as those exerted by CD4+CD25+ regulatory T cells, which derive from Th0 in the presence of TGF-?, but in the absence of IL-6. If regulatory mechanisms fail, the autoimmune attack is perpetuated. Over the past three decades different aspects of the above pathogenic scenario have been investigated. In particular, a defect in immunoregulation affecting CD4+CD25+ regulatory T cells (T-regs) has been demonstrated in AIH, particularly at diagnosis or during relapse. Advances in the study of autoreactive T cells have occurred mostly in AIH type 2, since the knowledge that CYP2D6 is the main autoantigen has enabled the characterization of both CD4 and CD8 T cells targeting this cytochrome. CD4 T cells from patients with type 2 AIH positive for the predisposing HLA allele DRB1*0701 recognize seven regions of CYP2D6, five of which are also recognized by CD8 T cells. High numbers of IFN-? producing CD4 T cells and CD8 T cells are associated with biochemical evidence of liver damage, suggesting a combined cellular immune attack.

Vergani, Diego; Mieli-Vergani, Giorgina

2008-01-01

357

[Fascioliasis case in the patient with hepatitis A].  

PubMed

There is some portion of patients with clinically manifested acute viral hepatitis, which are seronegative to hepatitis A markers. They have to be differentiated with other patients with B, C, D hepatitis, mechanical jaundice, etc. Such clinical cases make physician to recall the parasitic diseases, such as fascioliasis, which affects hepatobiliary system, causes prolongation of cholestasis and dystrophic changes in the biliary tract and likely to cause liver cirrhosis. In the presented case the initial diagnosis was severe acute Hepatitis A (anti-HAV IgM+), though the peripheral blood examination showed moderate eosinophilia, ultrasound investigation revealed multiple sites of damage in the liver, which made us to consider fascioliasis, the latter was confirmed by the serological analysis. Appropriate medical treatment was effective and the state of the patient has improved. PMID:15855700

Kvitashvili, M A; Dvali, Sh A; Kokaia, I Zh

2005-03-01

358

Enteric hepatitis viruses  

PubMed Central

Hepatitis viruses are infectious agents that can infect liver and cause inflammation. The infection triggers immune response against infected cells that leads to the destruction of hepatic cells. This destruction has two consequences: leaking ALT and AST liver enzymes which increases during the course of disease and accumulation of bilirubin- a red pigmented compound released from dead red cells- which causes the yellow coloration of eyes and skin. These viruses transmit through diverse routes i.e. blood transfusion, sexual contacts and consuming water or food contaminated by feces. Enteric hepatitis viruses use the latter route for transmission; hence their outbreaks are more common in underdeveloped countries. There are currently two distinguished enteric hepatitis viruses, hepatitis A and hepatitis E. These viruses belong to different family of viruses and their epidemiological characteristics are different. These infections can be diagnosed by an ELISA for IgM antibody. A vaccine has been developed in last decade of twentieth century for hepatitis A virus, which is administered mostly in the developed world i.e. U.S and Japan. Treatment for these infections is mostly supportive; however, in the case of fulminant hepatitis the liver transplantation might be necessary.

Tahaei, Seyed Mohammad Ebrahim; Zali, Mohammad Reza

2012-01-01

359

ALLYLISOPROPYLACETAMIDE INDUCES RAT HEPATIC ORNITHINE DECARBOXYLASE (JOURNAL VERSION)  

EPA Science Inventory

Allylisopropylacetamide (AIA) did not cause DNA damage in rat liver. The porphyrinogenic research drug did strongly induce the activity (25-fold) of rat hepatic enzyme ornithine decarboxylase (ODC). By either the oral or the subcutaneous route AIA produced a long lasting inductio...

360

Hepatitis E in liver biopsies from patients with acute hepatitis of clinically unexplained origin.  

PubMed

Hepatitis E virus (HEV) is a small RNA virus and the infectious agent of hepatitis E that occurs worldwide either as epidemics in Asia caused by genotype 1 and 2 or as sporadic disease in industrialized countries induced by genotype 3 and 4. The frequency might be underestimated in central Europe as a cause of acute hepatitis. Therefore, we analyzed on liver biopsies, if cases of acute hepatitis with clinically unknown or obscure diagnosis were actually caused by the infection with HEV. We included 221 liver biopsies retrieved from the files of the institute of pathology during the years 2000 till 2010 that were taken from patients with acute hepatitis of obscure or doubtful diagnosis. From all biopsies RNA was extracted, prepared, and subjected to RT-PCR with specific primers. Amplified RNA was detected in 7 patients, sequenced and the genotype 3 could be determined in four of the seven of positive specimens from 221 samples. Histopathology of the biopsies revealed a classic acute hepatitis with cholestatic features and in some cases confluent necrosis in zone 3. Histology in a cohort of matched patients was less severe and showed more eosinophils. The analysis of the immune response by subtyping of liver infiltrating lymphocytes showed circumstantial evidence of adaptive immune reaction with CD 8 positive CTLs being the dominant lymphocyte population. In conclusion, in doubtful cases of acute hepatitis of unknown origin, HEV infection should be considered as etiology in central Europe. We demonstrate for the first time that the diagnosis can be made in paraffin-embedded liver biopsies reliably when no serum is available and also the genotype can be determined. The analysis of the immune response by subtyping of liver infiltrating lymphocytes indicates an adaptive mechanism suggesting in analogy with HAV, HBV and HCV that the virus itself is not cytopathic but liver damage is due to immune reaction. PMID:24379784

Drebber, Uta; Odenthal, Margarete; Aberle, Stephan W; Winkel, Nadine; Wedemeyer, Inga; Hemberger, Jutta; Holzmann, Heidemarie; Dienes, Hans-Peter

2013-01-01

361

[Diclofenac-associated acute cholestatis hepatitis].  

PubMed

Diclofenac is an anti-inflammatory analgesic which is widely used in the therapy of inflammatory joint pain. Diclofenac hepatotoxicity ranges from asymptomatic elevation of transaminase activity to significant liver disease. 31 cases of diclofenac-induced hepatitis with five associated deaths have been already reported in the English, French and Spanish literature. We report the case of a 64-year-old patient who was admitted to the hospital with an icteric hepatitis of sudden onset. The only drug that was taken before admission was diclofenac in a daily dose of 150-200 mg because of a spondylodiscitis. Work-up of the patient included ERCP, laparoscopy and liver biopsy and excluded other reasons of a cholestatic hepatitis. Discontinuation of diclofenac resulted in normalization of transaminase activity and bilirubin concentration within four months. The frequent use of diclofenac and the possibility of fatal liver damage highlights the need that diclofenac-toxicity should be considered in the differential diagnosis of acute cholestatic hepatitis. PMID:9654706

Hackstein, H; Mohl, W; Püschel, W; Stallmach, A; Zeitz, M

1998-05-01

362

Ethanol-Induced Changes in Trichloroethylene Toxicity.  

National Technical Information Service (NTIS)

This project was aimed at determining the extent to which the metabolism of trichloroethylene (TCE) to trichloroacetate (TCA) was responsible for its hepatotoxic effects in rodents. Originally ethanol co-administration was to be used to selectively decrea...

R. J. Bull

1988-01-01

363

[Treatment of viral hepatitis].  

PubMed

Chronic forms of viral B,C and D hepatitis and fulminant hepatitis represent a serious healthcare problem. The study deals with the changes in the strategy in treating these diseases. During the chronic active hepatitis caused by the B hepatitis virus, the main aim of treatment is to cease multiplication of viruses, eliminate the clinical symptoms, prevent the development of cirrhosis, or the origin of hepatocellular carcinoma. The authors analyze the possibilities of the application of corticosteroids, viricidal drugs (vidarabin and interferons) and other medicaments (acyclovir, zidovudin, duramin, gancyclovir, chinacrin, and others) besides corticosteroids, interleukin 2 and tymozin from the group of immunomodulators were tested. The testing included the factor stimulating the colonies of granulocytes and myeloblasts and other substances. The therapy of acute protracted B hepatitis by means of interferon still requires controlled studies. Superinfection by D virus in chronic carriers of HBsAG causes chronic hepatitis which quickly leads to the development of cirrhosis. The therapy on basis of alpha interferon decreases the RNA virus D hepatitis serum level and leads to an improvement in the development of chronic hepatitis in half of the patients. Therapy of chronic C hepatitis on basis of corticosteroids is ineffective, and can be dangerous. Acyclovir is proved to be ineffective as well. The open study indicated certain positive results in application of interferon. The fulminant hepatitis can be defined as a development of encephalopathy and a decrease of the prothrombin time to less than 50% in the course of acute hepatitis. The break-point in the therapy of fulminant hepatitis took place in association with the performance of the transplantation of the liver. Impossibility to transplant the liver means that the effect of therapy of fulminant hepatitis is merely of supportive value. Majority of patients die due to neurologic complications, namely unmanageable oedema of the brain. But still, neither the antioedema therapy, e.g. on basis of manitol, as well as by means of corticosteroids, hemodialysis, hemofiltration, plasmapheresis and hemoperfusion, nor the treatment on basis of E1 prostaglandine improved the survival of patients. (Tab. 2, Ref. 82). PMID:8556359

Miguet, J; Hrusovský, S

1995-09-01

364

Ethanol-Induced Increase of Agouti-Related Protein (AgRP) Immunoreactivity in the Arcuate Nucleus of the Hypothalamus of C57BL/6J, but not 129/SvJ, Inbred Mice  

PubMed Central

Background The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor, pro-opiomelanocortin (POMC). Previous research has shown that MC receptor (MCR) agonists reduce, and MCR antagonists increase, ethanol consumption in rats and mice. Consistently, genetic deletion of the endogenous MCR antagonist, agouti-related protein (AgRP), causes reductions of ethanol-reinforced lever pressing and binge-like ethanol drinking in C57BL/6J mice. Ethanol also has direct effects on the central MC system, as chronic exposure to an ethanol-containing diet causes significant reductions of ?-melanocyte stimulating hormone (?-MSH) immunoreactivity in specific brain regions of Sprague-Dawley rats. Together, these observations suggest that the central MC system modulates neurobiological responses to ethanol. To further characterize the role of the MC system in responses to ethanol, here we compared AgRP and ?-MSH immunoreactivity in response to an acute injection of saline or ethanol between high ethanol drinking C57BL/6J mice and moderate ethanol drinking 129/SvJ mice. Methods Mice received an intraperitoneal (i.p.) injection of ethanol (1.5 g/kg or 3.5 g/kg; mixed in 0.9% saline) or an equivolume of 0.9% saline. Two hours after injection, animals were sacrificed and their brains were processed for AgRP and ?-MSH immunoreactivity. Results Results indicated that acute ethanol administration triggered a dose-dependent increase in AgRP immunoreactivity in the arcuate (ARC) of C57BL/6J mice, an effect that was not evident in the 129/SvJ strain. Although acute administration of ethanol did not influence ?-MSH immunoreactivity, C57BL/6J mice had significantly greater overall ?-MSH immunoreactivity in the ARC, dorsomedial, and lateral regions of the hypothalamus relative to the 129/SvJ strain. In contrast, C57BL/6J mice displayed significantly lower ?-MSH immunoreactivity in the medial amygdala. Conclusions The results show that acute ethanol exposure has direct effects on endogenous AgRP activity in ethanol preferring C57BL/6J mice. It is suggested that ethanol-induced increases in AgRP may be part of a positive feedback system that stimulates excessive binge-like ethanol drinking in C57BL/6J mice. Inherent differences in ?-MSH immunoreactivity may contribute to differences in neurobiological responses to ethanol that are characteristically observed between the C57BL/6J and 129/SvJ inbred strains of mice.

Cubero, Inmaculada; Navarro, Montserrat; Carvajal, Francisca; Lerma-Cabrera, Jose Manuel; Thiele, Todd E.

2011-01-01

365

Changes in the proteome of Huh7 cells induced by transient expression of hepatitis D virus RNA and antigens  

Microsoft Academic Search

Hepatitis delta virus (HDV) infection of human hepatocytes infected with the hepatitis B virus (HBV) is associated with increased liver damage and risk of fulminant disease. Although considerable progress has been made towards the elucidation of the mechanisms of HDV replication and pathogenesis, little is still known about the host factors involved in the different steps of the replication cycle.

Sérgio Mota; Marta Mendes; Deborah Penque; Ana V. Coelho; Celso Cunha

2008-01-01

366

Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy  

Microsoft Academic Search

Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). Liver injury is believed to occur following free radical damage to endothelial cells of the sinusoids and small hepatic veins. Glutathione the main antioxidant of the cytosol becomes depleted following chemotherapy. Animal studies have shown that glutamine infusions can maintain

AP Goringe; S Brown; U O’Callaghan; J Rees; S Jebb; M Elia; CH Poynton

1998-01-01

367

Hepatitis Foundation International  

MedlinePLUS

... nutrients in the food you eat into muscles, energy, hormones, blood clotting factors and immune factors. ImageT4 ... GIVES Amazon will donate 0.5% of the price of your eligible AmazonSmile purchases to Hepatitis Foundation ...

368

Hepatitis C: Mental Health  

MedlinePLUS

... National Observances Veterans Day Memorial Day Celebrating America's Freedoms Special Events Adaptive Sports Program Creative Arts Festival ... and behavior.) Having hepatitis C can have an impact on several areas of your life. Many people ...

369

Chemoembolization of hepatic malignancy  

Microsoft Academic Search

Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization (TACE) represents an essential\\u000a component of interventional oncology. This article discusses patient selection, procedure technique, results, and complications\\u000a associated with TACE.

Carin F. Gonsalves; Daniel B. Brown

370

Chemoembolization of hepatic malignancy  

Microsoft Academic Search

Treatment of primary and secondary hepatic malignancies with transarterial chemoembolization represents an essential component\\u000a of interventional oncology. This article discusses patient selection, procedure technique, results, and complications associated\\u000a with transarterial chemoembolization.

Carin F. Gonsalves; Daniel B. Brown

2009-01-01

371

Living with Hepatitis B  

MedlinePLUS

... for anyone with hepatitis B because of the risk of eating contaminated shellfish. Raw or undercooked shellfish can contain a bacteria called Vibrio vulnificus, which is very toxic to the liver. Talk to your doctor about ...

372

Protective Effect of Brazilian Propolis against Liver Damage with Cholestasis in Rats Treated with ?-Naphthylisothiocyanate  

PubMed Central

We examined the protective effect of Brazilian propolis against liver damage with cholestasis in rats treated with ?-naphthylisothiocyanate (ANIT) in comparison with that of vitamin E (VE). Rats orally received Brazilian propolis ethanol extract (BPEE) (25, 50, or 100?mg/kg), VE (250?mg/kg) or vehicle at 12?h after intraperitoneal injection of ANIT (75?mg/kg) and were killed 24?h after the injection. Vehicle-treated rats showed liver cell damage and cholestasis, judging from the levels of serum marker enzymes and components. The vehicle group had increased serum total cholesterol, triglyceride, phospholipid, and lipid peroxide levels, increased hepatic lipid peroxide, reduced glutathione, and ascorbic acid levels and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. BPEE (50?mg/kg) administered to ANIT-treated rats prevented liver cell damage and cholestasis and attenuated these serum and hepatic biochemical changes except hepatic ascorbic acid, although administered BPEE (25 or 100?mg/kg) was less effective. VE administered to ANIT-treated rats prevented liver cell damage, but not cholestasis, and attenuated increased serum lipid peroxide level, increased hepatic lipid peroxide level and myeloperoxidase activity, and decreased hepatic superoxide dismutase activity. These results indicate that BPEE protects against ANIT-induced liver damage with cholestasis in rats more effectively than VE.

Nakamura, Tadashi; Ohta, Yoshiji; Ohashi, Koji; Ikeno, Kumiko; Watanabe, Rie; Tokunaga, Kenji; Harada, Nobuhiro

2013-01-01

373

Children with hepatitis C  

Microsoft Academic Search

Hepatitis C affects thousands of children throughout the world. Most children acquire the virus through vertical transmission,\\u000a although parenteral routes of acquisition are also common. Hepatitis C progresses slowly, with mild biopsy findings and no\\u000a symptoms in most children and in many adults. However, significant liver inflammation and fibrosis can occur in childhood.\\u000a Trials of antiviral therapy with interferon and

Girish Subba Rao; Jean Pappas Molleston

2005-01-01

374

Hepatitis B: Approved Drugs for Children  

MedlinePLUS

... Children Clinical Trials HBF Drug Watch Prevention and Vaccination Prevention Measures Hepatitis B Vaccine Hepatitis A Vaccine ... Series Frequently Asked Questions General Information Prevention and Vaccination Hepatitis B Blood Tests Living with Hepatitis B ...

375

Hepatitis B Guidelines for Pregnant Women  

MedlinePLUS

Hepatitis B Foundation Cause for a Cure www.hepb.org Hepatitis B Foundation · 3805 Old Easton Road, Doylestown PA 18902 · 215-489-4900 · info@hepb.org Hepatitis B Guidelines for Pregnant Women What is hepatitis B? ...

376

Mechanisms of hepatic fibrogenesis.  

PubMed

Substantial improvements in the treatment of chronic liver disease have accelerated interest in uncovering the mechanisms underlying hepatic fibrosis and its resolution. Activation of resident hepatic stellate cells into proliferative, contractile, and fibrogenic cells in liver injury remains a dominant theme driving the field. However, several new areas of rapid progress in the past 5-10 years also have taken root, including: (1) identification of different fibrogenic populations apart from resident stellate cells, for example, portal fibroblasts, fibrocytes, and bone-marrow-derived cells, as well as cells derived from epithelial mesenchymal transition; (2) emergence of stellate cells as finely regulated determinants of hepatic inflammation and immunity; (3) elucidation of multiple pathways controlling gene expression during stellate cell activation including transcriptional, post-transcriptional, and epigenetic mechanisms; (4) recognition of disease-specific pathways of fibrogenesis; (5) re-emergence of hepatic macrophages as determinants of matrix degradation in fibrosis resolution and the importance of matrix cross-linking and scar maturation in determining reversibility; and (6) hints that hepatic stellate cells may contribute to hepatic stem cell behavior, cancer, and regeneration. Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease. PMID:18471545

Friedman, Scott L

2008-05-01

377

Hepatitis E virus.  

PubMed

Hepatitis E virus (HEV) is responsible for major outbreaks of acute hepatitis in developing countries where it was first described as a waterborne disease, transmitted by drinking water contaminated with feces. Attention was focused on HEV in developed countries and its associated diseases in recent years as a result of increasing reports of autochthonous infections. Hepatitis E is the zoonotic cause of these acute infections, and mainly in men over 50 years of age. The clinical manifestations and laboratory abnormalities of hepatitis E infections in immunocompetent patients cannot be distinguished from those caused by other hepatitis viruses. HEV is a major public health concern in immunocompromised patients because their infections can become chronic. The specific etiology of cases of hepatitis E infection can be diagnosed by serological testing and detecting viral RNA. Ribavirin is currently the reference treatment for HEV infections in immunocompromised patients. Several vaccines have proved safe and effective in clinical trials, but none have been approved for use in Europe yet. PMID:23608595

Abravanel, F; Lhomme, S; Dubois, M; Peron, J-M; Alric, L; Kamar, N; Izopet, J

2013-07-01

378

Mangafodipir Protects against Hepatic Ischemia-Reperfusion Injury in Mice  

PubMed Central

Introduction and Aim Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. Methods Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. Results Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. Conclusions Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.

Coriat, Romain; Leconte, Mahaut; Kavian, Niloufar; Bedda, Sassia; Nicco, Carole; Chereau, Christiane; Goulvestre, Claire; Weill, Bernard

2011-01-01

379

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease.  

PubMed

Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients. PMID:24269813

Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

2014-01-01

380

Bronchobiliary fistula after radiofrequency thermal ablation of hepatic tumor.  

PubMed

A broad spectrum of complications can occur after radiofrequency (RF) ablation of hepatic tumors, even though it has been accepted as a safe and effective technique for unresectable hepatic tumors. Recently, the rare complication of brochobiliary fistula was encountered after RF ablation in a patient with a metastatic tumor from stomach cancer. It was assumed to have developed from collateral damage to the adjacent diaphragm and lung base as well as biloma formation at the ablation zone. Symptomatic improvement was achieved by conservative management with an external drainage catheter, but the fistula was still persistent on a 2-month follow-up image. PMID:15758140

Kim, Young-Sun; Rhim, Hyunchul; Sung, Jung Hwan; Kim, Sung Kyu; Kim, Yongsoo; Koh, Byung Hee; Cho, On Koo; Kwon, Sung-Joon

2005-03-01

381

Psychological presentations without hepatic involvement in Wilson disease.  

PubMed

Wilson disease is an autosomal recessive inborn error of copper metabolism that leads to neurologic symptoms and variable degrees of hepatic damage. The most common characteristic signs clinically are liver disease, psychiatric disease, neurologic disease, or a combination of these. Early recognition by means of clinical signs and an early initiation of therapy using chelators or zinc-salts are essential for a good outcome and prognosis. This report describes a male suffering from Wilson disease who exhibited an unusual presentation that included psychological manifestations without hepatic involvement. He was initially treated for attention-deficit hyperactivity disorder and a seizure disorder until brain imaging established the diagnosis of Wilson disease. PMID:16996405

Lin, Jainn-Jim; Lin, Kuang-Lin; Wang, Huei-Shyong; Wong, Mun-Ching

2006-10-01

382

Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows  

PubMed Central

Background Hepatic lipidosis or fatty liver disease is a major metabolic disorder of high-producing dairy cows that compromises animal performance and, hence, causes heavy economic losses worldwide. This syndrome, occurring during the critical transition from gestation to early lactation, leads to an impaired health status, decreased milk yield, reduced fertility and shortened lifetime. Because the prevailing clinical chemistry parameters indicate advanced liver damage independently of the underlying disease, currently, hepatic lipidosis can only be ascertained by liver biopsy. We hypothesized that the condition of fatty liver disease may be accompanied by an altered profile of endogenous metabolites in the blood of affected animals. Results To identify potential small-molecule biomarkers as a novel diagnostic alternative, the serum samples of diseased dairy cows were subjected to a targeted metabolomics screen by triple quadrupole mass spectrometry. A subsequent multivariate test involving principal component and linear discriminant analyses yielded 29 metabolites (amino acids, phosphatidylcholines and sphingomyelines) that, in conjunction, were able to distinguish between dairy cows with no hepatic lipidosis and those displaying different stages of the disorder. Conclusions This proof-of-concept study indicates that metabolomic profiles, including both amino acids and lipids, distinguish hepatic lipidosis from other peripartal disorders and, hence, provide a promising new tool for the diagnosis of hepatic lipidosis. By generating insights into the molecular pathogenesis of hepatic lipidosis, metabolomics studies may also facilitate the prevention of this syndrome.

2014-01-01

383

Classical and Modern Approaches Used for Viral Hepatitis Diagnosis  

PubMed Central

Context: Viral hepatitis diagnosis is an important issue in the treatment procedure of this infection. Late diagnosis and delayed treatment of viral hepatitis infections can lead to irreversible liver damages and occurrence of liver cirrhosis and hepatocellular carcinoma. A variety of laboratory methods including old and new technologies are being applied to detect hepatitis viruses. Here we have tried to review, categorize, compare and illustrate the classical and modern approaches used for diagnosis of viral hepatitis. Evidence Acquisition: In order to achieve a comprehensive aspect in viral hepatitis detection methods, an extensive search using related keywords was done in major medical library and data were collected, categorized and summarized in different sections. Results: Analyzing of collected data resulted in the wrapping up the hepatitis virus detection methods in separate sections including 1) immunological methods such as enzyme immunoassay (EIA), radio-immunoassay (RIA) immuno-chromatographic assay (ICA), and immuno-chemiluminescence 2) molecular approaches including non-amplification and amplification based methods, and finally 3) advanced biosensors such as mass-sensitive, electrical, electrochemical and optical based biosensors and also new generation of detection methods. Conclusions: Detection procedures in the clinical laboratories possess a large diversity; each has their individual advantages and facilities' differences.

Heiat, Mohammad; Ranjbar, Reza; Alavian, Seyed Moayed

2014-01-01

384

Acute liver damage and ecstasy ingestion.  

PubMed Central

Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery. Images Figure 1 Figure 2 Figure 3

Ellis, A J; Wendon, J A; Portmann, B; Williams, R

1996-01-01

385

Detection of Hepatitis in Blood.  

National Technical Information Service (NTIS)

To evaluate new hepatitis B antigen (HBAg) assay techniques and their influence on acute and chronic post transfusion hepatitis, recipients of blood units found to be positive by reverse passive hemagglutination (RPHA) and radioimmunoassay (RIA) were pros...

G. L. Gitnick

1975-01-01

386

Preventing hepatitis B or C  

MedlinePLUS

Hepatitis B and C virus infection cause irritation and swelling of the liver. Since both of these infections ... children should receive their first dose of the hepatitis B vaccine at birth, and complete the series of ...

387

Acute hepatic failure in children.  

PubMed Central

Many diseases may present as acute hepatic failure in the pediatric age group, including viral hepatitis A and B, adverse drug reactions, both toxic and "hepatitic," and inherited metabolic disorders such as tyrosinemia, alpha 1 antitrypsin deficiency, and Wilson's disease. Management is primarily supportive, with care taken to anticipate the known complications of hepatic failure. Few "curative" therapies are known, although attempts at stimulating hepatic regeneration may be helpful. Images FIG. 1 FIG. 3 FIG. 4

Riely, C. A.

1984-01-01

388

Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol.  

PubMed

Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH(-)) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH(-) and hepatic ADH-normal (ADH(+)) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ?1.5-fold greater in ADH(-) vs. ADH(+) deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH(-) deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis. PMID:20478324

Kaphalia, Bhupendra S; Bhopale, Kamlesh K; Kondraganti, Shakuntala; Wu, Hai; Boor, Paul J; Ansari, G A Shakeel

2010-08-01

389

Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol  

PubMed Central

Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH?) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH? and hepatic ADH-normal (ADH+) deer mice fed 1, 2 or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ~1.5-fold greater in ADH? vs. ADH+ deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH? deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu, Hai; Boor, Paul J.; Ansari, G.A. Shakeel

2010-01-01

390

[Effects of hepatitis B virus X protein on chronic hepatitis B pathophysiology].  

PubMed

The infection by hepatitis B virus often promotes chronic liver inflammation which progresses to cirrhosis and hepatocellular carcinoma in a high percentage of patients. The persistent activation of the immune system causes an incessant liver damage, which fosters a disorganized stimulation of tissue repair and remodelling phenomena. In turn, the viral protein X (HBx) is essential for virus replication and therefore for the maintenance of chronic infection. However, the important oncogenic potential of HBx seems to reside, on one hand, in its ability to integrate into cellular DNA and, additionally, in the transactivation of different cellular signaling pathways involved in cell growth regulation, apoptosis and DNA repair. HBx also interacts with proteasome subunits and notably affects mitochondrial electric potential, thus altering cellular calcium homeostasis. Finally, this review discusses the pathogenic role of HBx in the progression of chronic hepatitis B through its effects on angiogenic, fibrogenic and oncogenic processes. PMID:23245531

Martín-Vílchez, Samuel; Moreno-Otero, Ricardo; Sanz-Cameno, Paloma

2013-06-01

391

Screening of subclinical hepatic encephalopathy  

Microsoft Academic Search

Background\\/Aims: Subclinical hepatic encephalopathy adversely affects daily functioning. The aim of this study was to determine which elements of daily life have predictive value for subclinical hepatic encephalopathy.Methods: The study was performed in 179 outpatients with liver cirrhosis. Subclinical hepatic encephalopathy was diagnosed using psychometric tests with normal values corrected for age (Number Connection Test A and the Digit Symbol

Michael Groeneweg; Wendy Moerland; Juan C Quero; Wim C. J Hop; Paul F Krabbe; Solko W Schalm

2000-01-01

392

Management of Chronic Hepatitis B  

Microsoft Academic Search

Chronic hepatitis B affects 400 million people worldwide. The criteria for initiating and stopping treatment are still under debate in spite of well-established agents for its treatment. Hepatitis B virus (HBV) DNA level has been shown to be a major determinant for disease progression, and the development of complications of cirrhosis and hepatocellular carcinoma, which often occur after hepatitis B

Ching-Lung Lai; Man-Fung Yuen

2011-01-01

393

Rifaximin Treatment in Hepatic Encephalopathy  

Microsoft Academic Search

Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrho- sis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent

Nathan M. Bass; Kevin D. Mullen; Arun Sanyal; Fred Poordad; Guy Neff; Carroll B. Leevy; Samuel Sigal; Muhammad Y. Sheikh; Kimberly Beavers; Todd Frederick; Lewis Teperman; Donald Hillebrand; Shirley Huang; Kunal Merchant; Audrey Shaw; Enoch Bortey; William P. Forbes

2010-01-01

394

Hepatic antigen-presenting cells and regulation of liver transplant outcome  

Microsoft Academic Search

In the steady state, hepatic antigen (Ag)-presenting cells (APC) generally dampen systemic inflammatory responses to gut-derived\\u000a Ags. Our studies focus on the role of specific liver APC populations, both non-parenchymal cells (dendritic cells [DC], Kupffer\\u000a cells, and hepatic stellate cells [HSC]) and parenchymal cells, in the molecular regulation of tissue damage (ischemia and\\u000a reperfusion [I\\/R] injury) and immunity following liver

Angus W. ThomsonDavid; David A. Geller; Chandrashekhar Gandhi; Noriko Murase; A. Jake Demetris; Donna Beer-Stolz

2011-01-01

395

Reduced Mobilisation of Hematopoietic Stem Cells After Hepatic Resection for Malignant Liver Disease  

Microsoft Academic Search

Recent studies have demonstrated that hematopoietic stem cells (HSCs) can mobilize following liver resection, thus contributing\\u000a to the repair of hepatic damage. Aim of this study has been to determine whether the nature of the hepatic lesion (benign\\u000a vs. malignant disease) can give rise to a different degree of mobilisation of HSCs. Two groups of patients were selected:\\u000a the first

Marinella Menegazzo; Paola Bagatella; Piero Marson; Carla Donadel; Giustina De Silvestro; Augusto Corsini

2008-01-01

396

Proteomic Analysis of Hepatic Tissue in Adult Female Zebrafish ( Danio rerio ) Exposed to Atrazine  

Microsoft Academic Search

Atrazine (ATZ), the most common herbicide, is a frequently observed contaminant in freshwater ecosystems. In the present study,\\u000a two-dimensional gel electrophoresis and matrix-assisted laser desorption\\/ionization tandem time-of-flight-mass spectrometry,\\u000a combined with histopathological analysis, were used to detect the hepatic damage in adult female zebrafish (Danio rerio) exposed to ATZ. More than 600 hepatic protein spots were detected in each gel with

Yuanxiang Jin; Xiangxiang Zhang; Dezhao Lu; Zhengwei Fu

397

Primary hepatic pregnancy.  

PubMed

A 25-year-old G2P1L1 woman with 18-week pregnancy presented with right hypochondriac pain and vomiting for the past 1 week. She had borderline vitals and a diffusely tender abdomen. Ultrasound revealed a live 18-week fetus attached to the undersurface of the liver with moderate ascites. Laparotomy was carried out which revealed 500 cc of hemoperitoneum with a primary hepatic pregnancy of the right lobe of liver and bleeding from the placental site. After extracting the fetus, the placenta was left inn situ and the abdomen was packed to control the bleeding as other hemostatic measures failed. Hepatic artery embolization was done after surgery followed by relaparotomy but the abdomen had to be repacked again as the patient was unstable with uncontrollable bleeding. The patient succumbed to DIC despite adequate replacement. In retrospect, the authors conclude that embolization could have been done before surgery and partial hepatic resection attempted in the first instance. PMID:23248513

Yadav, Reena; Raghunandan, Chitra; Agarwal, Swati; Dhingra, Shilpa; Chowdhary, Sarita

2012-10-01

398

Juvenile autoimmune hepatitis: Spectrum of the disease  

PubMed Central

Juvenile autoimmune hepatitis (JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific and organ-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoantibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.

Maggiore, Giuseppe; Nastasio, Silvia; Sciveres, Marco

2014-01-01

399

Characterization of a precipitating antigen detected in the serum of patients with viral hepatitis.  

PubMed

During a search for the aetiological agent of non-A non-B hepatitis, a precipitating antigen was detected in the sera of some patients during the acute phase of their illness. The antigen was detected by agar gel diffusion using antibody from convalescent sera obtained from patients with non-A non-B hepatitis, and from haemophiliac sera. The antigen was usually detected early in the patient's illness, disappearing as liver function tests returned to normal. In some patients specific antibody appeared during the convalescent phase of the disease. The antigen does not appear to be specific for non-A non-B hepatitis, as it could be detected with similar frequency in patients with hepatitis A or hepatitis B and some patients with other liver disorders. Biochemical and biophysical studies suggest that the antigen is probably an abnormal lipoprotein produced as a result of acute liver damage. PMID:6409994

Zhuang, H; Coulepis, A G; Locarnini, S A; Kaldor, J; Marshall, J A; Gust, I D

1983-01-01

400

Chronic ecstasy (3,4-methylenedioxymetamphetamine) abuse: a recurrent and unpredictable cause of severe acute hepatitis.  

PubMed

Fifteen reports of hepatitis induced by ecstasy (MDMA, 3,4-methylenedioxymetamphetamine) have been published over the last 3 years. With the increasing enthusiasm for "Rave" parties, the incidence appears to be increasing, and is an important and often concealed cause of acute hepatitis in young people. We report two cases of recurrent ecstasy-associated hepatitis where the interval between drug consumption and jaundice was variable and the link therefore initially obscured. Liver biopsies of both patients showed acute hepatitis. One was of relatively mild degree, and the other was severe, with features suggesting auto-immune hepatitis. Both cases resolved spontaneously. A high index of suspicion and careful specific enquiry are necessary to make the diagnosis and warn the patient to abstain in future, since subsequent attacks may be fatal and insidious chronic damage may occur. PMID:8912157

Fidler, H; Dhillon, A; Gertner, D; Burroughs, A

1996-10-01

401

Maintaining Hepatic Stem Cell Gene Expression on Biological and Synthetic Substrata  

PubMed Central

Abstract The liver is a highly resilient organ that possesses enormous regenerative capacity. This is mediated mainly through the most abundant cell type found in the liver, the hepatocyte. When the regenerative capacity of the hepatocyte is compromised, during chronic or acute liver injury, hepatic progenitor cells (HPCs) are activated to replace the damaged tissue. The HPC resides in a laminin-rich environment; as HPCs differentiate toward a hepatic or biliary fate, the extracellular matrix (ECM) composition changes, influencing cell behavior. To assess the impact that the biological ECM and the synthetic ECM have on the maintenance of hepatic stem cell gene expression, a murine hepatic stem cell line was employed. We demonstrate that hepatic stem cell gene expression could be maintained using a biological or synthetic substratum, but not on plastic alone.

Lucendo-Villarin, Baltasar; Khan, Ferdous; Pernagallo, Salvatore; Bradley, Mark; Iredale, John P.

2012-01-01

402

Hepatic stem cell niches  

PubMed Central

Stem cell niches are special microenvironments that maintain stem cells and control their behavior to ensure tissue homeostasis and regeneration throughout life. The liver has a high regenerative capacity that involves stem/progenitor cells when the proliferation of hepatocytes is impaired. In recent years progress has been made in the identification of potential hepatic stem cell niches. There is evidence that hepatic progenitor cells can originate from niches in the canals of Hering; in addition, the space of Disse may also serve as a stem cell niche during fetal hematopoiesis and co