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1

Antioxidant and hepatoprotective effect of Garcinia indica fruit rind in ethanol-induced hepatic damage in rodents  

PubMed Central

The protective effects of aqueous extracts of the fruit rind of Garcinia indica (GIE) on ethanol-induced hepatotoxicity and the probable mechanisms involved in this protection were investigated in rats. Liver damage was induced in rats by administering ethanol (5 g/kg, 20% w/v p.o.) once daily for 21 days. GIE at 400 mg/kg and 800 mg/kg and the reference drug silymarin (200 mg/kg) were administered orally for 28 days to ethanol treated rats, this treatment beginning 7 days prior to the commencement of ethanol administration. Levels of marker enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), triglyceride (sTG), albumin (Alb) and total protein (TP) were evaluated in serum. Antioxidant parameters (reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)), hepatic triglycerides (hTG) and the lipid peroxidation marker malondialdehyde (MDA) were determined in liver. GIE and silymarin elicited significant hepatoprotective activity by attenuating the ethanol–elevated levels of AST, ALT, ALP, sTG, hTG and MDA and restored the ethanol-depleted levels of GSH, SOD, CAT, GPx, GR, Alb and TP. GIE 800 mg/kg demonstrated greater hepatoprotection than GIE 400 mg/kg. The present findings indicate that hepatoprotective effects of GIE in ethanol-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation in liver. PMID:23554565

Ashar, Hardik; Srinath, Sudhamani

2012-01-01

2

BHT blocks NfkB activation and Ethanol-Induced Brain Damage  

Technology Transfer Automated Retrieval System (TEKTRAN)

Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol induced degeneration is unknown, but is not glutamate neurotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol ...

3

Possible role of oxygen free radicals in ethanol-induced gastric mucosal damage in rats  

Microsoft Academic Search

The involvement of oxygen free radicals in the development of the ethanol-induced gastric mucosal damage has been investigated. We found that oral administration of superoxide dismutase reduced the incidence of ethanol-induced mucosal lesions. Reduction of superoxide dismutase activity by diethyldithiocarbamate led to a pronounced aggravation of mucosal damage. Inhibition of the chloride-bicarbonate channel by a stilbene derivative also aggravated the

Istvan Szelenyi; Kay Brune

1988-01-01

4

Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in rats  

PubMed Central

Chronic ethanol feeding decreases expression of adiponectin by adipocytes and circulating adiponectin. Adiponectin treatment during chronic ethanol feeding prevents liver injury in mice. Chronic ethanol feeding also increases oxidative and endoplasmic reticulum (ER) stress in adipose tissue. Here we tested the hypothesis that supplemental taurine, an amino acid that functions as a chemical chaperone/osmolyte and enhances cellular anti-oxidant activity, would prevent ethanol-induced decreases in adiponectin expression and attenuate liver injury. Serum adiponectin concentrations decreased as early as 4–7 days after feeding rats a 36% ethanol diet. This rapid decrease was associated with increased oxidative, but not ER, stress in subcutaneous adipose tissue. Taurine prevented ethanol-induced oxidative stress and increased inflammatory cytokine expression in adipose tissue. Ethanol feeding also rapidly decreased expression of transcription factors regulating adiponectin expression (C/EBP?, PPAR? and PPAR?) in subcutaneous adipose tissue. Taurine prevented the ethanol-induced decrease in C/EBP? and PPAR? normalizing adiponectin mRNA and serum adiponectin concentrations. In the liver, taurine prevented ethanol-induced oxidative stress and attenuated TNF-? expression and steatosis, at least in part, by increasing expression of genes involved in fatty acid oxidation. In conclusion In subcutaneous adipose tissue, taurine decreased ethanol-induced oxidative stress and cytokine expression, as well as normalized expression of adiponectin mRNA. Taurine prevented ethanol-induced decreases in serum adiponectin; normalized adiponectin was associated with a reduction in hepatic oxidative stress, TNF-? expression and steatosis. Taken together, these data demonstrate that taurine has important protective effects against ethanol-induced tissue injury in both adipose and liver. PMID:19296466

Chen, Xiaocong; Sebastian, Becky M.; Tang, Hui; McMullen, Megan M.; Axhemi, Armend; Jacobsen, Donald W.; Nagy, Laura E.

2009-01-01

5

A novel role for GAPDH-MAO B cascade in ethanol-induced cellular damage  

PubMed Central

Background Alcoholism is a major psychiatric condition at least partly associated with ethanol-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and may contribute to ethanol-induced cell damage. Methods Expression of GAPDH and MAO B protein was studied in human glioblastoma and neuroblastoma cell lines exposed to physiological concentrations of ethanol. Expression of these proteins was also examined in the prefrontal cortex from human subjects with alcohol dependence and in rats fed with an ethanol diet. Co-immunoprecipitation, subcellular fractionation, and luciferase assay were used to address nuclear GAPDH-mediated MAO B activation. To test the effects of inactivation, RNAi and pharmacological intervention were used, and cell damage was assessed by TUNEL and H2O2 measurements. Results Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-beta-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to ethanol. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (Deprenyl) and rasagiline (Azilect) can block this cascade. Conclusions Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which may play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies. PMID:20022592

Ou, Xiao-Ming; Stockmeier, Craig A.; Meltzer, Herbert Y.; Overholser, James C.; Jurjus, George J.; Dieter, Lesa; Chen, Kevin; Lu, Deyin; Johnson, Chandra; Youdim, Moussa B.H.; Austin, Mark C.; Luo, Jia; Sawa, Akira; May, Warren; Shih, Jean C.

2009-01-01

6

PPAR?/? modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity.  

PubMed

Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Toward this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-?/? (PPAR?/?) has been shown to inhibit steatosis, the present study examined the role of PPAR?/? in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Ppar?/?-null mice were fed either a control or 4% ethanol diet and examined after 4-7 months of treatment. Ethanol fed Ppar?/?-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Ppar?/?-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPAR?/? in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Ppar?/?-null mice. Evidence suggests that PPAR?/? modulates pyridoxal kinase activity by altering Km, consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPAR?/? prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity. PMID:23851158

Goudarzi, Maryam; Koga, Takayuki; Khozoie, Combiz; Mak, Tytus D; Kang, Boo-Hyon; Fornace, Albert J; Peters, Jeffrey M

2013-09-15

7

The effect of thalidomide on ethanol-induced gastric mucosal damage in mice: involvement of inflammatory cytokines and nitric oxide.  

PubMed

Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue. PMID:25478868

Amirshahrokhi, Keyvan; Khalili, Ali-Reza

2015-01-01

8

The protective effects of the combination of sodium ferulate and oxymatrine on ethanol-induced liver damage in mice.  

PubMed

The aim of this study was to investigate the effects of the combination of SF and OMT on ethanol-induced liver damage in mice. The animal liver wet/dry weight (W/D) ratio and liver tissue histopathology, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA), superoxidase dismutase (SOD), C-reactive protein (CRP), interleukin-6 (IL-6), and nuclear factor ?B (NF-?B) levels were measured. The data indicated that the levels of ALT, AST, TG, CRP, IL-6, NF-?B and MDA significantly decreased and that SOD activity improved after treatment with the combination of SF and OMT; the same effects were not observed with the same dose of SF or OMT when used alone. These results indicated that the combination of SF and OMT had a protective effect on ethanol-induced liver damage in mice and that antioxidation and anti-inflammatory effects might be involved in this protective mechanism. PMID:24441025

Pei, Xiaokun; Wang, Wei; Miao, Ningshu; Xu, Mengxin; Zhang, Chunlei; Sun, Mengmeng; Xu, Mingbo; Liu, Zhifeng

2014-01-01

9

Physicochemical properties, antioxidant activities and protective effect against acute ethanol-induced hepatic injury in mice of foxtail millet (Setaria italica) bran oil.  

PubMed

This study was designed to investigate physicochemical characterization of the oil extracted from foxtail millet bran (FMBO), and the antioxidant and hepatoprotective effects against acute ethanol-induced hepatic injury in mice. GC-MS analysis revealed that unsaturated fatty acids (UFAs) account for 83.76% of the total fatty acids; in particular, the linoleic acid (C18:2) is the predominant polyunsaturated fatty acid (PUFA), and the compounds of squalene and six phytosterols (or phytostanols) were identified in unsaponifiable matter of FMBO. The antioxidant activity examination of FMBO in vitro showed highly ferric-reducing antioxidant power and scavenging effects against DPPH· and HO· radicals. Furthermore, the protective effect of FMBO against acute hepatic injuries induced by ethanol was verified in mice. In this, intragastric administration with different dosages of FMBO in mice ahead of acute ethanol administration could observably antagonize the ethanol-induced increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and the hepatic malondialdehyde (MDA) levels, respectively, along with enhanced hepatic superoxide dismutase (SOD) levels relative to the control. Hepatic histological changes were also observed and confirmed that FMBO is capable of attenuating ethanol-induced hepatic injury. PMID:24909671

Pang, Min; He, Shujian; Wang, Lu; Cao, Xinmin; Cao, Lili; Jiang, Shaotong

2014-08-01

10

Solanesol protects human hepatic L02 cells from ethanol-induced oxidative injury via upregulation of HO-1 and Hsp70.  

PubMed

In present study, we showed that the mRNA and protein levels of HO-1 and Hsp70 in solanesol-treated L02 cells were significantly increased. The induction of the HO-1 by solanesol is majorly achieved via enhancing the nuclear translocation and transactivity of Nrf2 through enhancement of Hsp90-Keap1 interaction, while solanesol-elevated Hsp70 is related with promoting the nuclear translocation of HSF1 through the involvement of chaperones interaction. Furthermore, the induction of HO-1 and Hsp70 by solanesol could protect against ethanol-induced liver injury, including significantly suppressing the elevation of the activities of LDH and AST, attenuating ethanol-induced increase of the MDA, ROS level and decrease of the GSH level. Moreover, solanesol also suppressed ethanol-induced apoptosis of L02 cells by inhibition of nuclear morphological damage, procaspase 3 and cleavage of caspase 3 and PARP, suggesting solanesol may be beneficial against ALD. Solanesol also promoted tBHQ-mediated protective effects. However, treatment cells with SnPP or PES markedly abrogated the protective effects of solanesol on ethanol-induced cell injury. These results strongly suggested that solanesol could protect ethanol-induced L02 cell damage, which might be attributed to the activation of HO-1 and Hsp70. PMID:25645596

Yao, Xiangyang; Bai, Qin; Yan, Dazhong; Li, Guilan; Lü, Chaotian; Xu, Hui

2015-04-01

11

Expression of Heat Shock Proteins and Cytokines in Response to Ethanol Induced Damage in the Small Intestine of ICR Mice  

PubMed Central

Background/Aims Ethanol administration causes intestinal epithelial cell damage by increasing intestinal permeability and the translocation of endotoxins from intestinal bacterial flora. Heat shock proteins (HSPs) are associated with recovery and protection from cell damage. The aim of the current study was to investigate differences in the expression of HSPs in the small intestine and the biochemical changes attributable to ethanol-induced intestinal damage. Methods Ethanol (20%) was injected intraperitoneally (2.75 g/kg, 5.5 g/kg, 8.25 g/kg) in ICR mice and the same volume of saline was administered to controls. After 1 hour, the proximal, middle, and distal segments were taken from the small intestine and the degree of damage was analyzed. In each segment, the expression of HSPs was analyzed by western blotting. The expression of inflammatory mediators including interleukin-1? (IL-1?), tumor necrosis factor-? (TNF-?), cyclooxygenase-2 (COX-2), and antioxidant enzyme such as glutathione-S-transferase were compared using real-time polymerase chain reaction assays. Results In the control group, HSP70 increased in all segments of small intestine. Additionally, increases in the expression of HSP40 and HSP90 in the distal regions and an increase in HSP32 in the middle regions were observed. After ethanol treatment, greater histological damage was observed in the distal small intestine and significant decreases in HSPs were observed generally. Increased expression of IL-1?, TNF-?, and COX-2 was observed in small intestinal tissues exposed to ethanol-induced damage. However, there was no significant difference in the expression of an antioxidant enzyme. Conclusions Significant differences in the expression of HSPs in different intestinal regions were observed. These differences may have been attributable to the distribution of intestinal bacteria. PMID:25349594

Lee, Sung Won; Choi, Dong Wook; Kim, Hee Jung; Nam, Yang Hoon; Choi, Dae Hee; Kang, Chang Don; Lee, Sung Joon; Chun, Wan Joo; Ryu, Young-Joon

2014-01-01

12

Ethanol-induced damage to mucosal capillaries of rat stomach. Ultrastructural features and effects of prostaglandin F2 beta and cysteamine  

SciTech Connect

Impairment of the mucosal microcirculation may contribute to ethanol-induced gastric mucosal damage. In this report, we describe diffuse and severe ultrastructural damage to the capillaries of the gastric glandular mucosa of the rat that occurred within 1 min after intragastric instillation of 100% ethanol. There was a gradient of damage in that endothelial cell structure was most severely disrupted in profiles of capillaries located close to the luminal surface but some morphologic evidence of damage was evident in the wall of capillary profiles to a mean depth of 256 micron. Capillary structure was generally normal in the deeper regions of the mucosa. Pretreatment with intragastric cysteamine, 30 mg/100 g, or intragastric prostaglandin F2 beta, 0.5 mg/100 g, significantly reduced the depth in the mucosa to which damage to capillaries extended. Pretreatment with intragastric prostaglandin F2 beta, 0.2 mg/100 g, afforded no significant protection. We conclude that a 1-min exposure to 100% ethanol induces striking damage to the microcirculation of glandular mucosa of the rat stomach with severe damage to capillary profiles near the lumen and sparing of capillary profiles near the muscularis mucosa, and pretreatment with the sulfhydryl agent, cysteamine, or with a large dose of prostaglandin F2 beta reduces the extent of but does not abolish ethanol-induced damage to gastric mucosal capillaries.

Trier, J.S.; Szabo, S.; Allan, C.H.

1987-01-01

13

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

14

Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity  

PubMed Central

In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin–proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, we describe the history and the importance of cellular hydrolytic systems, followed by a description of each catabolic pathway and the differential modulation of each by ethanol exposure. Overall, the evidence for an involvement of these catabolic systems in the pathogenesis of alcoholic liver disease is quite strong. It underscores their importance, not only as effective means of cellular recycling and eventual energy generation, but also as essential components of cellular defense. PMID:25462063

Donohue, Jr., Terrence M.; Thomes, Paul G.

2014-01-01

15

Ginseng, the Root of Panax ginseng C.A. Meyer, Protects Ethanol-Induced Gastric Damages in Rat through the Induction of Cytoprotective Heat-Shock Protein 27  

Microsoft Academic Search

Ginseng, the root of Panax ginseng C.A. Meyer, has been reported to exert preventive effects on gastropathy via anti-oxidative and anti-inflammatory actions.\\u000a In this study, we investigated the protective effects of ginseng against ethanol-induced gastric damages in rat. To examine\\u000a the preventive effect of ginseng, rats received two different ginseng extracts, A and B, 1 h prior to the administration of

Marie Yeo; Dong-Kyu Kim; Sung Won Cho; Hee Do Hong

2008-01-01

16

Dietary Zinc Deficiency Exaggerates Ethanol-Induced Liver Injury in Mice: Involvement of Intrahepatic and Extrahepatic Factors  

PubMed Central

Clinical studies have demonstrated that alcoholics have a lower dietary zinc intake compared to health controls. The present study was undertaken to determine the interaction between dietary zinc deficiency and ethanol consumption in the pathogenesis of alcoholic liver disease. C57BL/6N mice were subjected to 8-week feeding of 4 experimental liquid diets: (1) zinc adequate diet, (2) zinc adequate diet plus ethanol, (3) zinc deficient diet, and (4) zinc deficient diet plus ethanol. Ethanol exposure with adequate dietary zinc resulted in liver damage as indicated by elevated plasma alanine aminotransferase level and increased hepatic lipid accumulation and inflammatory cell infiltration. Dietary zinc deficiency alone increased hepatic lipid contents, but did not induce hepatic inflammation. Dietary zinc deficiency showed synergistic effects on ethanol-induced liver damage. Dietary zinc deficiency exaggerated ethanol effects on hepatic genes related to lipid metabolism and inflammatory response. Dietary zinc deficiency worsened ethanol-induced imbalance between hepatic pro-oxidant and antioxidant enzymes and hepatic expression of cell death receptors. Dietary zinc deficiency exaggerated ethanol-induced reduction of plasma leptin, although it did not affect ethanol-induced reduction of white adipose tissue mass. Dietary zinc deficiency also deteriorated ethanol-induced gut permeability increase and plasma endotoxin elevation. These results demonstrate, for the first time, that dietary zinc deficiency is a risk factor in alcoholic liver disease, and multiple intrahepatic and extrahepatic factors may mediate the detrimental effects of zinc deficiency. PMID:24155903

Sun, Xinguo; Song, Zhenyuan; McClain, Craig J.; Zhou, Zhanxiang

2013-01-01

17

Carbon monoxide alleviates ethanol-induced oxidative damage and inflammatory stress through activating p38 MAPK pathway  

SciTech Connect

Stress-inducible protein heme oxygenase-1(HO-1) is well-appreciative to counteract oxidative damage and inflammatory stress involving the pathogenesis of alcoholic liver diseases (ALD). The potential role and signaling pathways of HO-1 metabolite carbon monoxide (CO), however, still remained unclear. To explore the precise mechanisms, ethanol-dosed adult male Balb/c mice (5.0 g/kg.bw.) or ethanol-incubated primary rat hepatocytes (100 mmol/L) were pretreated by tricarbonyldichlororuthenium (II) dimmer (CORM-2, 8 mg/kg for mice or 20 ?mol/L for hepatocytes), as well as other pharmacological reagents. Our data showed that CO released from HO-1 induction by quercetin prevented ethanol-derived oxidative injury, which was abolished by CO scavenger hemoglobin. The protection was mimicked by CORM-2 with the attenuation of GSH depletion, SOD inactivation, MDA overproduction, and the leakage of AST, ALT or LDH in serum and culture medium induced by ethanol. Moreover, CORM-2 injection or incubation stimulated p38 phosphorylation and suppressed abnormal Tnfa and IL-6, accompanying the alleviation of redox imbalance induced by ethanol and aggravated by inflammatory factors. The protective role of CORM-2 was abolished by SB203580 (p38 inhibitor) but not by PD98059 (ERK inhibitor) or SP600125 (JNK inhibitor). Thus, HO-1 released CO prevented ethanol-elicited hepatic oxidative damage and inflammatory stress through activating p38 MAPK pathway, suggesting a potential therapeutic role of gaseous signal molecule on ALD induced by naturally occurring phytochemicals. - Highlights: • CO alleviated ethanol-derived liver oxidative and inflammatory stress in mice. • CO eased ethanol and inflammatory factor-induced oxidative damage in hepatocytes. • The p38 MAPK is a key signaling mechanism for the protective function of CO in ALD.

Li, Yanyan; Gao, Chao; Shi, Yanru; Tang, Yuhan; Liu, Liang; Xiong, Ting; Du, Min [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Xing, Mingyou [Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Liu, Liegang [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Yao, Ping, E-mail: yaoping@mails.tjmu.edu.cn [Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Ministry of Education Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China); Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030 (China)

2013-11-15

18

Binge Ethanol-Induced HDAC3 Down-Regulates Cpt1? Expression Leading to Hepatic Steatosis and Injury  

PubMed Central

Background Recently, we have demonstrated that acute alcohol exposure due to binge drinking leads to hepatic steatosis with the deregulation of hepatic histone deacetylase (HDAC) expression. Various class I, II, and IV HDACs were down-regulated, whereas expression of HDAC3 was solely up-regulated. Hence, in the present work, we specifically examined the mechanistic role of HDAC3 in the development of hepatic steatosis occurring in response to binge alcohol administration. Methods C57BL/6 mice were gavaged 3 times with ethanol (EtOH) at a dose of 4.5 g/kg. HDAC inhibitor, Trichostatin A (TSA) was simultaneously injected intraperitoneally at a dose of 1 mg/kg. Hepatic steatosis, injury, expression of HDAC3 and carnitine palmitoyltransferase 1? (CPT1?) were evaluated. HDAC3 and histone H3 acetylation levels at the Cpt1? promoter were analyzed by chromatin immunoprecipitation (ChIP). Results The binge EtOH-mediated increase in HDAC3 was prevented by simultaneous administration of HDAC inhibitor, TSA, which markedly attenuated hepatic steatosis and injury. Importantly, HDAC3 inhibition was able to normalize the down-regulation of Cpt1? expression. Causal role of HDAC3 in the transcriptional repression of Cpt1? was demonstrated by increased HDAC3 binding at the thyroid receptor element site in the Cpt1? distal promoter region. Further, a resultant decrease in the transcriptionally permissive histone H3 lysine 9 acetylation in the proximal promoter region near the transcriptional start site was observed. Notably, TSA treatment reduced HDAC3 binding and increased H3K9 acetylation at Cpt1? promoter leading to increased Cpt1? expression. These molecular events resulted in attenuation of binge alcohol-induced hepatic steatosis. Conclusions These findings provide insights into potential epigenetic mechanisms underlying transcriptional regulation of Cpt1? in the hepatic steatosis occurring in response to binge EtOH administration. PMID:23905631

Kirpich, Irina; Zhang, Jingwen; Gobejishvili, Leila; Kharebava, Giorgi; Barker, David; Ghare, Smita; Joshi-Barve, Swati; McClain, Craig J.; Barve, Shirish

2014-01-01

19

Protective effect of Opuntia ficus indica f. inermis prickly pear juice upon ethanol-induced damages in rat erythrocytes.  

PubMed

Juice from the fruit of the cactus Opuntia ficus indica is claimed to possess several health-beneficial properties. The present study was carried out to determine whether O. ficus indica f. inermis fruit extract might have a protective effect upon physiological and morphological damages inflicted to erythrocytes membrane by chronic ethanol poisoning, per os, in rat. Chemical analysis of the extract revealed the presence of polyphenols, flavonoids, ascorbic acid, carotenoids, and betalains. Ethanol administration (3 g/kg b.w, per day for 90 days) induced an increase of malondialdehyde (MDA) and carbonylated proteins levels and a decrease of glutathione (GSH) level in erythrocyte. Ethanol administration also reduced the scavenging activity in plasma and enhanced erythrocytes hemolysis, as compared to control rats. In addition, ethanol intake increased the erythrocyte shape index by +895.5% and decreased the erythrocyte diameter by -61.53% as compared to controls. In animals also given prickly pear juice during the same experimental period, the studied parameters were much less shifted. This protective effect was found to be dose-dependent. It is likely that the beneficial effect of the extract is due to the high content of antioxidant compounds. PMID:22445806

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

2012-05-01

20

Interleukin-32? attenuates ethanol-induced liver injury by the inhibition of cytochrome P450 2E1 expression and inflammatory responses.  

PubMed

Alcohol abuse and alcoholism lead to alcoholic liver disease (ALD), which is a major type of chronic liver disease worldwide. Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. However, the role of IL-32 in chronic liver disease has not been reported. In the present paper, we tested the effect of IL-32? on ethanol-induced liver injury in IL-32?-overexpressing transgenic mice (IL-32? mice) after chronic ethanol feeding. Male C57BL/6 and IL-32? mice (10-12 weeks old) were fed on a Lieber-DeCarli diet containing 6.6% ethanol for 6 weeks. IL-32?-transfected HepG2 and Huh7 cells, as well as primary hepatocytes from IL-32? mice, were treated with or without ethanol. The hepatic steatosis and damage induced by ethanol administration were attenuated in IL-32? mice. Ethanol-induced cytochrome P450 2E1 expression and hydrogen peroxide levels were decreased in the livers of IL-32? mice, primary hepatocytes from IL-32? mice and IL-32?-overexpressing human hepatic cells. The ethanol-induced expression levels of cyclo-oxygenase-2 (COX-2) and IL-6 were reduced in the livers of IL-32? mice. Because nuclear transcription factor ?B (NF-?B) is a key redox transcription factor of inflammatory responses, we examined NF-?B activity. Ethanol-induced NF-?B activities were significantly lower in the livers of IL-32? mice than in wild-type (WT) mice. Furthermore, reduced infiltration of natural killer cells, cytotoxic T-cells and macrophages in the liver after ethanol administration was observed in IL-32? mice. These data suggest that IL-32? prevents ethanol-induced hepatic injury via the inhibition of oxidative damage and inflammatory responses. PMID:25583360

Lee, Dong Hun; Kim, Dae Hwan; Hwang, Chul Ju; Song, Sukgil; Han, Sang Bae; Kim, Youngsoo; Yoo, Hwan Soo; Jung, Young Suk; Kim, Soo Hyun; Yoon, Do Young; Hong, Jin Tae

2015-05-01

21

Subcellular location of secretory proteins retained in the liver during the ethanol-induced inhibition of hepatic protein secretion in the rat  

SciTech Connect

Ethanol administration inhibits the secretion of proteins by the liver, resulting in their hepatocellular retention. Experiments were designed in this study to determine the subcellular location of the retained secretory proteins. Ethanol was administered acutely to nonfasted rats by gastric intubation, whereas control animals received an isocaloric dose of glucose. Two hours after intubation, when maximum blood ethanol levels (45 mM) were observed, (/sup 3/H)leucine and (/sup 14/C)fucose were injected simultaneously into the dorsal vein of the penis. The labelling of secretory proteins was determined in the liver and plasma at various time periods after label injection. Ethanol treatment decreased the secretion of both leucine- and fucose-labeled proteins into the plasma. This inhibition of secretion was accompanied by a corresponding increase in the hepatic retention of both leucine- and fucose-labeled immunoprecipitable secretory proteins. At the time of maximum inhibition of secretion, leucine labeled secretory proteins located in the Golgi apparatus represented about 50% of the accumulated secretory proteins in the livers of the ethanol-treated rats, whereas the remainder was essentially equally divided among the rough and smooth endoplasmic reticulum and cytosol. Because fucose is incorporated into secretory proteins almost exclusively in the Golgi complex, fucose-labeled proteins accumulated in the livers of the ethanol-treated rats mainly in the Golgi apparatus, with the remainder located in the cytosol. These results show that ethanol administration causes an impaired movement of secretory proteins along the secretory pathway, and that secretory proteins accumulate mainly, but not exclusively, in the Golgi apparatus.

Volentine, G.D.; Tuma, D.J.; Sorrell, M.F.

1986-01-01

22

An opium alkaloid-papaverine ameliorates ethanol-induced hepatotoxicity: Diminution of oxidative stress  

Microsoft Academic Search

In this communication, we show the modulatory potential of papaverine, an opium alkaloid and a well known vasodilator agent\\u000a on the ethanol-induced hepatic oxidative stress in male Wistar rats. Ethanol treatment (50% v\\/v) enhanced lipid peroxidation\\u000a significantly accompanied by a decline in the activities of glutathione peroxidase (G-Px), glutathione reductase (GR) and\\u000a depletion in levels of hepatic glutathione (GSH). Ethanol

Ramesh Chandra; Ritu Aneja; Charu Rewal; Rama Konduri; Sujaka K. Dass; Shefali Agarwal

2000-01-01

23

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

24

Protective action of antioxidants on hepatic damage induced by griseofulvin.  

PubMed

Erythropoietic protoporphyria (EPP) is a disease associated with ferrochelatase deficiency and characterized by the accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver, and skin. In some cases, a severe hepatic failure and cholestasis were observed. Griseofulvin (Gris) develops an experimental EPP with hepatic manifestations in mice such as PROTO IX accumulation followed by cellular damage as wells as necrotic and inflammatory processes. The antioxidant defense system was also altered. The aim was to evaluate the possible protective effect of different antioxidant compounds: trolox (Tx), ascorbic acid (Asc), the combination Tx and Asc, melatonin (Mel), and the polyphenols: ellagic acid, quercetin, chlorogenic acid, caffeic acid, gallic acid, and ferulic acid on liver damage and oxidative stress markers in a mouse model of EPP. Coadministration of Gris with Tx, Asc, and its combination, or Mel mainly affected heme biosynthetic pathway, resulting in a decrease in ALA-S activity which was increased by Gris, while the tested polyphenols exerted a protective effect on oxidative stress, decreasing lipid peroxidation and the activity of some antioxidant enzymes. In conclusion, antioxidant compounds can only protect partially against the liver damage induced by Gris, reducing oxidative stress or acting on heme regulation. PMID:24523661

Martinez, M del C; Afonso, S G; Buzaleh, A M; Batlle, A

2014-01-01

25

Protective Action of Antioxidants on Hepatic Damage Induced by Griseofulvin  

PubMed Central

Erythropoietic protoporphyria (EPP) is a disease associated with ferrochelatase deficiency and characterized by the accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver, and skin. In some cases, a severe hepatic failure and cholestasis were observed. Griseofulvin (Gris) develops an experimental EPP with hepatic manifestations in mice such as PROTO IX accumulation followed by cellular damage as wells as necrotic and inflammatory processes. The antioxidant defense system was also altered. The aim was to evaluate the possible protective effect of different antioxidant compounds: trolox (Tx), ascorbic acid (Asc), the combination Tx and Asc, melatonin (Mel), and the polyphenols: ellagic acid, quercetin, chlorogenic acid, caffeic acid, gallic acid, and ferulic acid on liver damage and oxidative stress markers in a mouse model of EPP. Coadministration of Gris with Tx, Asc, and its combination, or Mel mainly affected heme biosynthetic pathway, resulting in a decrease in ALA-S activity which was increased by Gris, while the tested polyphenols exerted a protective effect on oxidative stress, decreasing lipid peroxidation and the activity of some antioxidant enzymes. In conclusion, antioxidant compounds can only protect partially against the liver damage induced by Gris, reducing oxidative stress or acting on heme regulation. PMID:24523661

Martinez, M. del C.; Afonso, S. G.; Buzaleh, A. M.; Batlle, A.

2014-01-01

26

Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice  

SciTech Connect

Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-? and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-?B (NF-?B) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-?B expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-?B expression and MPO accumulation in ethanol-induced gastric tissue.

Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

2013-10-01

27

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

28

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

29

Ethanol-Induced Conditioned Taste Avoidance  

PubMed Central

Background Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, LiCl, are exaggerated in drug sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. Methods In Experiment 1, fluid deprived Lewis and Fischer rats were given 5 min access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically-guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Results Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. Conclusion The results suggest that the suppressive effects of ethanol on CS intake are mediated by both rewarding and aversive consequences, varying as a function of dose. PMID:19120065

Liu, Chuang; Showalter, John; Grigson, Patricia Sue

2009-01-01

30

Ethanol-Induced Upregulation of 10-Formyltetrahydrofolate Dehydrogenase Helps Relieve Ethanol-Induced Oxidative Stress  

PubMed Central

Alcoholism induces folate deficiency and increases the risk for embryonic anomalies. However, the interplay between ethanol exposure and embryonic folate status remains unclear. To investigate how ethanol exposure affects embryonic folate status and one-carbon homeostasis, we incubated zebrafish embryos in ethanol and analyzed embryonic folate content and folate enzyme expression. Exposure to 2% ethanol did not change embryonic total folate content but increased the tetrahydrofolate level approximately 1.5-fold. The expression of 10-formyltetrahydrofolate dehydrogenase (FDH), a potential intracellular tetrahydrofolate reservoir, was increased in both mRNA and protein levels. Overexpressing recombinant FDH in embryos alleviated the ethanol-induced oxidative stress in ethanol-exposed embryos. Further characterization of the zebrafish fdh promoter revealed that the ?124/+40 promoter fragment was the minimal region required for transactivational activity. The results of site-directed mutagenesis and binding analysis revealed that Sp1 is involved in the basal level of expression of fdh but not in ethanol-induced upregulation of fdh. On the other hand, CEBP? was the protein that mediated the ethanol-induced upregulation of fdh, with an approximately 40-fold increase of fdh promoter activity when overexpressed in vitro. We concluded that upregulation of fdh involving CEBP? helps relieve embryonic oxidative stress induced by ethanol exposure. PMID:24277932

Hsiao, Tsun-Hsien; Lin, Chia-Jen; Chung, Yi-Shao; Lee, Gang-Hui; Kao, Tseng-Ting; Chang, Wen-Ni; Chen, Bing-Hung; Hung, Jan-Jong

2014-01-01

31

Autophagy and ethanol-induced liver injury  

PubMed Central

The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism. Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients, endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury. PMID:19291817

Jr, Terrence M Donohue

2009-01-01

32

Diosmin Protects against Ethanol-Induced Gastric Injury in Rats: Novel Anti-Ulcer Actions  

PubMed Central

Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-? (TNF-?) levels along with nuclear factor kappa B (NF-?B) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses. PMID:25821971

Arab, Hany H.; Salama, Samir A.; Omar, Hany A.; Arafa, El-Shaimaa A.; Maghrabi, Ibrahim A.

2015-01-01

33

EFFECTS OF N-ACETYLCYSTEINE ON ETHANOL-INDUCED HEPATOTOXICITY IN RATS FED VIA TOTAL ENTERAL NUTRITION.  

Technology Transfer Automated Retrieval System (TEKTRAN)

It has been suggested that oxidative stress plays a role in the development of alcoholic liver damage but it remains unclear how important that role is and what the relationship is between oxidative stress, ethanol-induced increases in endotoxin derived from increased gut permeability to bacteria; c...

34

Brain growth during ethanol-induced hypoplasia.  

PubMed

The inhibition of fetal brain growth resulting from in utero ethanol exposure may impair central nervous system (CNS) development and thereby result in mental retardation. Studies of ethanol-induced brain hypoplasia using chick embryos have shown that the early development of the chick is significantly growth inhibited by a single dose of ethanol (1.0 g/kg) given at the start of incubation (day 0). However, this level of ethanol exposure has been reported to have no effect on chick weight measured at hatching, suggesting that the weights of ethanol-treated chicks were regained during their development. The present experiments were undertaken to determine the biochemical changes associated with the varying growth rates believed to occur in the alcohol-treated embryos. The results indicated that between days 5 and 8 of development, the rates of DNA and protein synthesis (measured as radioactive thymidine and leucine incorporation, respectively) were inhibited by ethanol. The growth inhibition was highly correlated with blood alcohol content and there were associated increases in brain prostaglandin E (PGE) levels relative to vehicle-treated embryos. Further, there was a significant, inverse correlation between brain cyclic AMP content and individual brain weight. By day 10, the ethanol-treated embryos remained smaller than controls but their rates of DNA and protein synthesis were comparable to those of control animals. The normal rates of synthesis observed on day 10 appeared to correlate with clearance of the ethanol dose and with restoration of normal brain levels of PGE relative to 10-day vehicle-dosed embryos. PMID:2830089

Pennington, S; Kalmus, G

1987-11-30

35

Protective Effects of the Traditional Herbal Formula Oryeongsan Water Extract on Ethanol-Induced Acute Gastric Mucosal Injury in Rats  

PubMed Central

This study was performed to evaluate the protective effect and safety of Oryeongsan water extract (OSWE) on ethanol-induced acute gastric mucosal injury and an acute toxicity study in rats. Acute gastric lesions were induced via intragastric oral administration of absolute ethanol at a dose of 5?mL/kg. OSWE (100 and 200?mg/kg) was administered to rats 2?h prior to the oral administration of absolute ethanol. The stomach of animal models was opened and gastric mucosal lesions were examined. Gastric mucosal injuries were evaluated by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and the activity of antioxidant enzymes. In the acute toxicity study, no adverse effects of OSWE were observed at doses up to 2000?mg/kg/day. Administration of OSWE reduced the damage by conditioning the gastric mucosa against ethanol-induced acute gastric injury, which included hemorrhage, hyperemia, and loss of epithelial cells. The level of MDA was reduced in OSWE-treated groups compared with the ethanol-induced group. Moreover, the level of GSH and the activity of antioxidant enzymes were significantly increased in the OSWE-treated groups. Our findings suggest that OSWE has a protective effect on the gastric mucosa against ethanol-induced acute gastric injury via the upregulation of antioxidant enzymes. PMID:23118790

Jeon, Woo-Young; Lee, Mee-Young; Shin, In-Sik; Lim, Hye-Sun; Shin, Hyeun-Kyoo

2012-01-01

36

Vanillyl nonanoate protects rat gastric mucosa from ethanol-induced injury through a mechanism involving calcitonin gene-related peptide.  

PubMed

Previous studies have demonstrated that capsaicin-sensitive sensory nerves are involved in the protection of gastric mucosa against damage by various stimuli and calcitoin gene-related peptide (CGRP) is a potential mediator in this process. This study was performed to explore the effect of vanillyl nonanoate, a capsaicin analog, on ethanol-induced gastric mucosal injury and the possible underlying mechanisms. A rat model of gastric mucosal injury was induced by oral administration of acidified ethanol and gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, the activities of caspase-3, catalase and superoxide dismutase (SOD), levels of CGRP, TNF-? and malondialdehyde (MDA). The results showed that acute administration of ethanol significantly increased gastric ulcer index concomitantly with increased cellular apoptosis, caspase-3 activity, TNF-? and MDA levels as well as decreased activities of catalase and SOD. Pretreatment with 1mg/kg vanillyl nonanoate significantly attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by increase of CGRP expression, and SOD activity and decrease of caspase-3 activity, TNF-? and MDA levels. The effects of vanillyl nonanoate were inhibited by capsazepine, an antagonist of capsaicin receptor. Our results suggested that vanillyl nonanoate was able to protect the gastric mucosa against ethanol-induced gastric mucosal injury. The underlying mechanism is related to stimulation of CGRP release and subsequent suppression of ethanol-induced inflammatory reaction, cellular apoptosis and oxidative stress. PMID:21640099

Luo, Xiu-Ju; Li, Nian-Sheng; Zhang, Yi-Shuai; Liu, Bin; Yang, Zhi-Chun; Li, Yuan-Jian; Dong, Xin-Rong; Peng, Jun

2011-09-01

37

Farnesoid X receptor regulates forkhead Box O3a activation in ethanol-induced autophagy and hepatotoxicity  

PubMed Central

Alcoholic liver disease encompasses a wide spectrum of pathogenesis including steatosis, fibrosis, cirrhosis, and alcoholic steatohepatitis. Autophagy is a lysosomal degradation process that degrades cellular proteins and damaged/excess organelles, and serves as a protective mechanism in response to various stresses. Acute alcohol treatment induces autophagy via FoxO3a-mediated autophagy gene expression and protects against alcohol-induced steatosis and liver injury in mice. Farnesoid X Receptor (FXR) is a nuclear receptor that regulates cellular bile acid homeostasis. In the present study, wild type and FXR knockout (KO) mice were treated with acute ethanol for 16 h. We found that ethanol treated-FXR KO mice had exacerbated hepatotoxicity and steatosis compared to wild type mice. Furthermore, we found that ethanol treatment had decreased expression of various essential autophagy genes and several other FoxO3 target genes in FXR KO mice compared with wild type mice. Mechanistically, we did not find a direct interaction between FXR and FoxO3. Ethanol-treated FXR KO mice had increased Akt activation, increased phosphorylation of FoxO3 resulting in decreased FoxO3a nuclear retention and DNA binding. Furthermore, ethanol treatment induced hepatic mitochondrial spheroid formation in FXR KO mice but not in wild type mice, which may serve as a compensatory alternative pathway to remove ethanol-induced damaged mitochondria in FXR KO mice. These results suggest that lack of FXR impaired FoxO3a-mediated autophagy and in turn exacerbated alcohol-induced liver injury. PMID:25460735

Manley, Sharon; Ni, Hong-Min; Williams, Jessica A.; Kong, Bo; DiTacchio, Luciano; Guo, Grace; Ding, Wen-Xing

2014-01-01

38

Farnesoid X receptor regulates forkhead Box O3a activation in ethanol-induced autophagy and hepatotoxicity.  

PubMed

Alcoholic liver disease encompasses a wide spectrum of pathogenesis including steatosis, fibrosis, cirrhosis, and alcoholic steatohepatitis. Autophagy is a lysosomal degradation process that degrades cellular proteins and damaged/excess organelles, and serves as a protective mechanism in response to various stresses. Acute alcohol treatment induces autophagy via FoxO3a-mediated autophagy gene expression and protects against alcohol-induced steatosis and liver injury in mice. Farnesoid X Receptor (FXR) is a nuclear receptor that regulates cellular bile acid homeostasis. In the present study, wild type and FXR knockout (KO) mice were treated with acute ethanol for 16h. We found that ethanol treated-FXR KO mice had exacerbated hepatotoxicity and steatosis compared to wild type mice. Furthermore, we found that ethanol treatment had decreased expression of various essential autophagy genes and several other FoxO3 target genes in FXR KO mice compared with wild type mice. Mechanistically, we did not find a direct interaction between FXR and FoxO3. Ethanol-treated FXR KO mice had increased Akt activation, increased phosphorylation of FoxO3 resulting in decreased FoxO3a nuclear retention and DNA binding. Furthermore, ethanol treatment induced hepatic mitochondrial spheroid formation in FXR KO mice but not in wild type mice, which may serve as a compensatory alternative pathway to remove ethanol-induced damaged mitochondria in FXR KO mice. These results suggest that lack of FXR impaired FoxO3a-mediated autophagy and in turn exacerbated alcohol-induced liver injury. PMID:25460735

Manley, Sharon; Ni, Hong-Min; Williams, Jessica A; Kong, Bo; DiTacchio, Luciano; Guo, Grace; Ding, Wen-Xing

2014-08-28

39

Delayed ethanol elimination and enhanced susceptibility to ethanol-induced hepatosteatosis after liver resection  

PubMed Central

AIM: To investigate ethanol-induced hepatic steatosis after liver resection and the mechanisms behind it. METHODS: First, the preliminary examination was performed on 6 sham-operated (Sham) and 30 partial hepatectomy (PH) male Wistar rats (8-wk-old) to evaluate the recovery of the liver weight and liver function after liver resection. PH rats were sacrificed at the indicated time points (4, 8, and 12 h; 1, 3, and 7 d) after PH. Second, the time point for the beginning of the chronic ethanol exposure (1 wk after sham- or PH-operation) was determined based on the results of the preliminary examination. Finally, pair-feeding was performed with a controlled diet or with a 5-g/dL ethanol liquid diet for 28 d in another 35 age-matched male Wistar rats with a one-week recovery after undergoing a sham- (n = 15) or PH-operation (n = 20) to evaluate the ethanol-induced liver injury after liver resection. Hepatic steatosis, liver function, fatty acid synthase (Fas) gene expression level, the expression of lipid metabolism-associated enzyme regulator genes [sterol regulatory element binding protein (Srebp)-1 and peroxisome proliferator-activated receptor (Ppar)-?], the mediators that alter lipid metabolism [plasminogen activator (Pai)-1 gene expression level and tumor necrosis factor (Tnf)-? production], and hepatic class-1 alcohol dehydrogenase (Adh1)-associated ethanol elimination were investigated in the 4 groups based on histological, immunohistochemical, biochemical, Western blotting, reverse transcriptase chain reaction, and blood ethanol concentration analyses. The relevant gene expression levels, liver weight, and liver function were assessed before and 1 wk after surgery to determine the subject’s recovery from the liver resection using the rats that had been subjected to the preliminary examination. RESULTS: In the PH rats, ethanol induced marked hepatic steatosis with impaired liver functioning, as evidenced by the accumulation of fatty droplets within the hepatocytes, the higher increases in their hepatic triglyceride and blood alanine aminotransferase and blood aspartate aminotransferase levels after the 28-d pair-feeding period. The Sham-ethanol rats, not the PH-ethanol rats, demonstrated the up-regulation of Srebp-1 and the down-regulation of Ppar-? mRNA expression levels after the 28-d pair-feeding period. The 28-d ethanol administration induced the up-regulation of Pai-1 gene expression level and an overproduction of TNF-? in the Sham and the PH rats; however, the effect was more significant in the PH rats. The PH-ethanol rats (n = 4) showed higher residual blood ethanol concentrations than did the Sham-ethanol rats (n = 6) after a 5-h fast (0.66 ± 0.4 mg/mL vs 0.2 ± 0.1 mg/mL, P < 0.05); these effects manifested without up-regulation of Adh1 gene expression, which was present in the Sham-ethanol group after the 28-d pair-feeding period. One week after the liver resection, the liver weight, function, the gene expression levels of Fas, Srebp-1, Ppar-?, Pai-1 and Tnf-? recovered; however, the Adh1 gene expression did not recover in rats. CONCLUSION: Desensitization to post-hepatectomy ethanol treatment and slow recovery from PH in Adh1 gene expression enhanced the susceptibility to ethanol-induced hepatic steatosis after PH in rats. PMID:25561792

Liu, Xu; Hakucho, Ayako; Liu, Jinyao; Fujimiya, Tatsuya

2014-01-01

40

Tumor Induced Hepatic Myeloid Derived Suppressor Cells Can Cause Moderate Liver Damage  

PubMed Central

Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage. PMID:25401795

Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J.; Korangy, Firouzeh; Greten, Tim F.

2014-01-01

41

Influence of gender on ethanol-induced ventricular myocyte contractile depression in transgenic mice with cardiac overexpression of alcohol dehydrogenase  

Microsoft Academic Search

Acute ethanol exposure depresses ventricular contractility and contributes to alcoholic cardiomyopathy in both men and women chronically consuming ethanol. However, a gender-related difference in the severity of myopathy exists with female being more sensitive to ethanol-induced tissue damage. Acetaldehyde (ACA), the major oxidized product of ethanol, has been implicated to play a role in the pathogenesis and gender-related difference of

Jinhong Duan; Lucy B. Esberg; Gang Ye; Anthony J Borgerding; Bonnie H Ren; Nicholas S Aberle; Paul N Epstein; Jun Ren

2003-01-01

42

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. PMID:22592597

Acevedo, María Belén; Nizhnikov, Michael E.; Spear, Norman E.; Molina, Juan C.; Pautassi, Ricardo Marcos

2012-01-01

43

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. PMID:22996800

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

2014-08-01

44

Decreased oxidative DNA damage and accelerated cell turnover in woodchuck hepatitis virus infected liver.  

PubMed

Infection of newborn woodchucks with woodchuck hepatitis virus (WHV) results in hepatocellular carcinoma (HCC). Since oxidative damage may be carcinogenic, we investigated the relationship between WHV infection and oxidative damage to hepatic lipids and DNA. Eastern woodchucks were infected with WHV. Hepatic lipid peroxidation was assessed in vitro in isolated hepatocytes by thiobarbituric acid reactive substances (TBARS). Oxidative DNA damage was assessed in vivo in snap-frozen livers by 8-hydroxy-2'-deoxyguanosine (8-OH-dG). The proliferation index (PI) and apoptotic index (AI) were also determined. WHV infection was associated with increased hepatic lipid peroxidation (0.51+/-0.04 nmols TBARS per mg protein for WHV+ hepatocytes vs. 0.38+/-0.04 for WHV negative controls, P<0.01). In contrast, the WHV+ livers exhibited less oxidative DNA damage than uninfected controls (11+/-5 vs. 38+/-8 8-OH-dG/10(6) dG, P<0.02). In WHV-infected animals PI and AI were increased, by >20-fold. We conclude that WHV infection is associated with increased in vitro lipid peroxidation and decreased in vivo oxidative DNA damage. The increased PI and AI in the WHV+livers suggest that rapid cell turnover dilutes 8-OH-dG concentration. PMID:12697246

O'Gorman, Molly A.; Sharma, Savitri; Groopman, John D.; Tennant, Bud C.; Tochkov, Ilia A.; Schwarz, Kathleen B.

2003-03-01

45

Hepatoprotective Activity of Bi-Herbal Ethanolic Extract on CCl4 Induced Hepatic Damage in Rats  

Microsoft Academic Search

The combined hepatoprotective effect of Bi- herbal ethanolic extract (BHEE) was evaluated against carbon tetra chloride (CCl4) induced hepatic damage in rats. Ethanolic extract from the leaves of Eclipta alba and seeds of Piper longum at a dose level of 50 mg\\/kg body weight was administered orally daily once for 14 days. The substantially elevated serum marker enzymes such as

P. Samudram; Rajeshwari Hari; R. Vasuki; A. Geetha; P. Sathiya Moorthi

2008-01-01

46

Preventive effects of geranylgeranylacetone on rat ethanol-induced gastritis  

PubMed Central

AIM: To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis. METHODS: One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) by gastrogavage; model control group and 2 model therapy groups that underwent gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups, while the same amount of NS, instead of geranylgeranylacetone was used in that model control group. The rats were then sacrificed and stomachs were removed. The injury level of the gastric mucosa was observed by light and electron microscopy, and the levels of prostaglandin 2 (PGE2), endothelin-1 (ET-1) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method. RESULTS: The gastric mucosal epidermal damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group were significantly higher than that of the normal control group (0 and 0 respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than that of the model control group (all P < 0.01). There was no statistically significant difference between the low-dose and high-dose model therapy groups. The expression value of plasma ET-1 of the model control group was higher than that of the normal control group (P < 0.01) and the 2 model therapy groups (all P < 0.01). The expression values of gastric mucosal PGE2 and serum NO of the model control group were lower than those of the normal control group (all P < 0.05) and the 2 model therapy groups (all P < 0.05). The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group (all P < 0.01) and the 2 model therapy groups (all P < 0.05). Scanning and transmission electron microscopy observation showed that in the model control group, the epithelial junctions were vague, the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group. However, in the 2 model therapy groups, damage to the intercellular joints and organelles was ameliorate relative to the model control group. CONCLUSION: Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion. The mechanism could be related to regulation of ET-1, NO and PGE2. PMID:22611321

Ning, Jian-Wen; Lin, Guan-Bin; Ji, Feng; Xu, Jia; Sharify, Najeeb

2012-01-01

47

Recent advances in estimating hepatic functional reserve in patients with chronic liver damage.  

PubMed

Preoperative estimation of liver functional reserve is important in liver surgery to prevent postoperative liver failure. Although the hepatic functional reserve of patients with chronic liver disease is generally evaluated by measuring indocyanine green dye retention at 15?min, no standard method of estimating regional liver function has been established to date. Several recently introduced imaging modalities, such as hepatobiliary scintigraphy and magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid, may be used to evaluate liver function. Here, we review recent advances in estimating hepatic functional reserve, mainly by radiological modalities, in patients with chronic liver damage. PMID:24606181

Imura, Satoru; Shimada, Mitsuo; Utsunomiya, Tohru

2015-01-01

48

Hepatitis  

MedlinePLUS

... to a liver condition called hepatitis . What Is Hepatitis? The liver is one of the body's powerhouses. ... option that is not always available or successful. Hepatitis A The hepatitis A virus (HAV) is transmitted ...

49

Hepatitis  

MedlinePLUS

... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ... the most common types of viral hepatitis. Continue Hepatitis A For kids, hep A is the most ...

50

Increased DNA damage in hepatitis C virus-related hepatocellular carcinoma.  

PubMed

One consequence of hepatitis C virus (HCV) infection is an elevated cancer risk. During chronic viral infection, deoxyribonucleic acid (DNA) damage is being induced by reactive oxygen and nitrogen species, which may play a pathogenic role in HCV-induced carcinogenesis. The study investigated DNA damage in peripheral blood lymphocytes from patients with hepatocellular carcinoma (HCC) and those with HCV infection with and without associated cirrhosis and normal controls. As a measure for genomic damage, the comet assay (single cell gel electrophoresis) was applied, which detects single- and double-strand breaks and alkali-labile sites through electrophoretic mobility of the resulting fragments. The levels of DNA damage were significantly higher in HCC and HCV-associated cirrhosis compared to HCV without cirrhosis and the control group. Patients presenting with DNA damage more than mean+two standard deviation of the controls had a 3.6-fold risk of having HCC more than those with undamaged DNA. HCV disease progression was the only discriminator predicting the extent of DNA damage. The accumulation of DNA damage is important in HCC evolution. DNA damage indicating intracellular oxidative and nitrative stress may lead to mutagenesis and consequently malignant transformation, which emphasizes the need to optimize the therapy for reducing the degree of genomic damage. PMID:25211328

Shawki, Shereen M; Meshaal, Safa S; El Dash, Aliaa S; Zayed, Naglaa A; Hanna, Mariam Onsy F

2014-12-01

51

Comparative Effects of Several Therapatic Agents on Hepatic Damage Induced by Acute Experimental Pancreatitis  

Microsoft Academic Search

Purpose The prognosis of acute pancreatitis (AP) depends upon the degree of pancreatic necrosis and the intensity of multisystem\\u000a organ failure. The liver contributes to the systemic manifestations of AP by releasing some cytokines. This study was undertaken\\u000a to examine comparative effects of melatonin, antioxidant mixture containing L(+)-ascorbic acid and N-acetyl cysteine, pentoxifylline and l-arginine on hepatic damage induced by

Mukaddes E?refo?lu; Mehmet Gül; Fahri Turan

2008-01-01

52

Effect of dried fruits of Solanum nigrum LINN against CCl4-induced hepatic damage in rats.  

PubMed

Ethanol extract of Solanum nigrum LINN was investigated for its hepatoprotective activity against CCl4-induced hepatic damage in rats. The ethanol extract showed remarkable hepatoprotective activity. The activity was evaluated using biochemical parameters such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and total bilirubin. The histopathological changes of liver sample in treated animals were compared with respect to control. PMID:14600413

Raju, Kuppuswamy; Anbuganapathi, Govindaraju; Gokulakrishnan, Velusamy; Rajkapoor, Balasubramanian; Jayakar, Balasundarm; Manian, Sellamuthu

2003-11-01

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. PMID:23964314

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. PMID:19221436

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

Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice  

SciTech Connect

Mice with unilateal striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. 14 references, 2 figures, 1 table.

Silverman, P.B.

1987-03-09

56

Protective effect of Brazilian propolis against hepatic oxidative damage in rats with water-immersion restraint stress.  

PubMed

In the present study we examined the protective effect of Brazilian propolis against hepatic oxidative damage in rats with water-immersion restraint stress (WIRS) in comparison with that of vitamin E (VE). Fasted rats orally received Brazilian green propolis ethanol extract (BPEE; 10, 50 or 100 mg/kg), VE (250 mg/kg) or vehicle at 30 min before the onset of WIRS. Exposure of vehicle-treated rats to 6 h of WIRS caused liver cell damage, judging from the levels of serum alanine aminotransferase and aspartate aminotransferease, increased hepatic lipid peroxide, NO(x) contents and myeloperoxidase activity, and decreased hepatic non-protein SH, ascorbic acid contents and superoxide dismutase activity. Preadministration of BPEE (50 or 100 mg/kg) or VE to the stressed rats protected against the hepatic damage and attenuated the increased hepatic lipid peroxide and NO(x) contents and myeloperoxidase activity and the decreased hepatic non-protein SH and ascorbic acid contents and superoxide dismutase activity. These protective effects of BPEE (50 mg/kg) were greater than those of BPEE (100 mg/kg) and were almost equal to those of VE. These results indicate that BPEE protects against hepatic oxidative damage in rats exposed to WIRS possibly through its antioxidant and antiinflammatory properties such as VE. PMID:22298415

Nakamura, Tadashi; Ohta, Yoshiji; Ohashi, Koji; Ikeno, Kumiko; Watanabe, Rie; Tokunaga, Kenji; Harada, Nobuhiro

2012-10-01

57

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

58

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. PMID:22260211

2012-01-01

59

Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice  

PubMed Central

The aim of the present study was to determine the preventive effect of the traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. (D. candidum), on CCl4-induced hepatic damage in mice. The CCl4-induced hepatic damage mice were treated with D. candidum, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG) and total cholesterol (TC) were determined. In addition, serum cytokine levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-? and interferon (IFN)-? were analyzed with kits, while liver tissues were analyzed using hematoxylin and eosin staining and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were significantly decreased when the mice were treated with 200 and 400 mg/kg D. candidum, as compared with the control mice (P<0.05). The lowest enzymatic activities were exhibited in the 400 mg/kg D. candidum group, which produced similar results to the positive control drug, silymarin. In addition, in the 400 mg/kg D. candidum group, the highest levels of TG and TC were observed among the treated groups. D. candidum-treated groups also demonstrated reduced levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-? and IFN-?. The sections of liver tissue examined during histopathology in the high concentration 400 mg/kg D. candidum group recovered well from CCl4 damage; however, the sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious degree. RT-PCR analysis was conducted on inflammation-associated genes, including nuclear factor (NF)-?B, I?B-?, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum group demonstrated significantly decreased mRNA expression levels of NF-?B, iNOS and COX-2, but an increased expression level of I?B-? when compared with the CCl4-treated control group. Furthermore, using NMR, 11 compounds were identified in the D. candidum leaf, whose functional contents may aid the preventive effect observed in the current study. Therefore, D. candidum may potentially contribute to the prevention of CCl4-induced hepatic damage in vivo. PMID:25120640

LI, GUI-JIE; SUN, PENG; WANG, QIANG; QIAN, YU; ZHU, KAI; ZHAO, XIN

2014-01-01

60

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

E-print Network

Expression of Ethanol-Induced Behavioral Sensitization Is Associated with Alteration of Chromatin), Amiens, France Abstract Background: Ethanol-induced behavioral sensitization (EIBS) is proposed to play in the development and the persistence of ethanol-related behaviors, we explored the involvement of epigenetic

Boyer, Edmond

61

Centrally formed acetaldehyde mediates ethanol-induced brain PKA activation.  

PubMed

Centrally formed acetaldehyde has proven to be responsible for several psychopharmacological effects induced by ethanol. In addition, it has been suggested that the cAMP-PKA signaling transduction pathway plays an important role in the modulation of several ethanol-induced behaviors. Therefore, we hypothesized that acetaldehyde might be ultimately responsible for the activation of this intracellular pathway. We used three pharmacological agents that modify acetaldehyde activity (?-lipoic acid, aminotriazole, and d-penicillamine) to study the role of this metabolite on EtOH-induced PKA activation in mice. Our results show that the injection of ?-lipoic acid, aminotriazole and d-penicillamine prior to acute EtOH administration effectively blocks the PKA-enhanced response to EtOH in the brain. These results strongly support the hypothesis of a selective release of acetaldehyde-dependent Ca(2+) as the mechanism involved in the neurobehavioral effects elicited by EtOH. PMID:25093700

Tarragon, E; Baliño, P; Aragon, C M G

2014-09-19

62

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

63

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

64

Hepatoprotective effect of biherbal ethanolic extract against paracetamol-induced hepatic damage in albino rats  

PubMed Central

Aim: The combined hepatoprotective effect of Bi-herbal ethanolic extract (BHEE) was evaluated against paracetamol induced hepatic damage in albino rats. Materials and Methods: Liver function tests and biochemical parameters were estimated using standard kits. Livers were quickly removed and fixed in 10% formalin and subjected to histopathological studies. Results: Ethanolic extract from the leaves of Aerva lanata and leaves of Achyranthes aspera at a dose level of 200 mg/kg, 400mg/kg body weight was administered orally once for 3 days. Substantially elevated serum marker enzymes such as SGOT, SGPT, ALP, due to paracetamol treatment were restored towards normal. Biochemical parameters like total protein, total bilirubin, total cholesterol, triglycerides, and urea were also restored towards normal levels. In addition, BHEE significantly decreased the liver weight of paracetamol intoxicated rats. Silymarin at a dose level of 25 mg/kg used as a standard reference also exhibited significant hepatoprotective activity against paracetamol induced hepatotoxicity. Conclusion: The results of this study strongly indicate that BHEE has got a potent hepatoprotective action against paracetamol induced hepatic damage in rats. PMID:23326091

Anantha, Krishna Chaitanya D.; Siva, Reddy Challa; Manohar, Reddy A.

2012-01-01

65

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice  

PubMed Central

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-? and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-?, IL-1?, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage. PMID:25866750

Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

2015-01-01

66

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice.  

PubMed

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-? and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-?, IL-1?, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage. PMID:25866750

Yi, Ruo-Kun; Song, Jia-Le; Lim, Yaung-Iee; Kim, Yong-Kyu; Park, Kun-Young

2015-03-01

67

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. PMID:22016781

Alvarez-Suarez, José M.; Dekanski, Dragana; Risti?, Slavica; Radonji?, Nevena V.; Petronijevi?, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

2011-01-01

68

Hepatic stellate cell-expressed endosialin balances fibrogenesis and hepatocyte proliferation during liver damage  

PubMed Central

Liver fibrosis is a reversible wound-healing response to injury reflecting the critical balance between liver repair and scar formation. Chronic damage leads to progressive substitution of liver parenchyma by scar tissue and ultimately results in liver cirrhosis. Stromal cells (hepatic stellate cells [HSC] and endothelial cells) have been proposed to control the balance between liver fibrosis and regeneration. Here, we show that endosialin, a C-type lectin, expressed in the liver exclusively by HSC and portal fibroblasts, is upregulated in liver fibrosis in mouse and man. Chronic chemically induced liver damage resulted in reduced fibrosis and enhanced hepatocyte proliferation in endosialin-deficient (ENKO) mice. Correspondingly, acute-liver-damage-induced hepatocyte proliferation (partial hepatectomy) was increased in ENKO mice. A candidate-based screen of known regulators of hepatocyte proliferation identified insulin-like growth factor 2 (IGF2) as selectively endosialin-dependent hepatocyte mitogen. Collectively, the study establishes a critical role of HSC in the reciprocal regulation of fibrogenesis vs. hepatocyte proliferation and identifies endosialin as a therapeutic target in non-neoplastic settings. PMID:25680861

Mogler, Carolin; Wieland, Matthias; König, Courtney; Hu, Junhao; Runge, Anja; Korn, Claudia; Besemfelder, Eva; Breitkopf-Heinlein, Katja; Komljenovic, Dorde; Dooley, Steven; Schirmacher, Peter; Longerich, Thomas; Augustin, Hellmut G

2015-01-01

69

Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury  

PubMed Central

Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. Methods: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress. PMID:25780705

Jang, Sun-Hee; Cho, Sung-woo; Yoon, Hyun-Min; Jang, Kyung-Jeon; Song, Chun-Ho; Kim, Cheol-Hong

2014-01-01

70

Hepatitis  

MedlinePLUS

... Disease Dementia Hospitalization & Palliative Care Related Topics on AIDS.gov Combating the Silent Epidemic of Viral Hepatitis: ... Adults and Adolescents Last revised: 05/07/2014 AIDS.gov HIV/AIDS Basics • Federal Resources • Using New ...

71

Hepatitis  

MedlinePLUS

... men, hepatitis A can be spread by direct anal/oral contact (rimming) or by contact with fingers, ... to protect yourself include avoiding rimming and other anal and oral contact. While condom use is essential ...

72

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. PMID:23403509

ZHAO, XIN

2013-01-01

73

Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain  

PubMed Central

Fetal alcohol syndrome is a neurological and developmental disorder caused by exposure of developing brain to ethanol. Administration of osmotin to rat pups reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in vivo and in vitro by reducing the protein levels of cleaved caspase-3, intracellular [Ca2+]cyt, and mitochondrial transmembrane potential collapse, and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced the ability of osmotin and adiponectin to protect neurons against ethanol-induced neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by osmotin, adiponectin, and metformin hold promise as a preventive therapy for fetal alcohol syndrome. PMID:24675468

Naseer, M I; Ullah, I; Narasimhan, M L; Lee, H Y; Bressan, R A; Yoon, G H; Yun, D J; Kim, M O

2014-01-01

74

Neuroprotective effect of osmotin against ethanol-induced apoptotic neurodegeneration in the developing rat brain.  

PubMed

Fetal alcohol syndrome is a neurological and developmental disorder caused by exposure of developing brain to ethanol. Administration of osmotin to rat pups reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in vivo and in vitro by reducing the protein levels of cleaved caspase-3, intracellular [Ca(2+)]cyt, and mitochondrial transmembrane potential collapse, and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced the ability of osmotin and adiponectin to protect neurons against ethanol-induced neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate-activated protein kinase), increased whereas Compound C, an inhibitor of AMPK pathway, reduced the ability of osmotin and adiponectin to protect against ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by osmotin, adiponectin, and metformin hold promise as a preventive therapy for fetal alcohol syndrome. PMID:24675468

Naseer, M I; Ullah, I; Narasimhan, M L; Lee, H Y; Bressan, R A; Yoon, G H; Yun, D J; Kim, M O

2014-01-01

75

Investigation of Antioxidant and Hepatoprotective Activity of Standardized Curcuma xanthorrhiza Rhizome in Carbon Tetrachloride-Induced Hepatic Damaged Rats  

PubMed Central

Curcuma xanthorrhiza (CX) has been used for centuries in traditional system of medicine to treat several diseases such as hepatitis, liver complaints, and diabetes. It has been consumed as food supplement and “jamu” as a remedy for hepatitis. Hence, CX was further explored for its potential as a functional food for liver related diseases. As such, initiative was taken to evaluate the antioxidant and hepatoprotective potential of CX rhizome. Antioxidant activity of the standardized CX fractions was determined using in vitro assays. Hepatoprotective assay was conducted against carbon tetrachloride- (CCl4-) induced hepatic damage in rats at doses of 125, 250, and 500?mg/kg of hexane fraction. Highest antioxidant activity was found in hexane fraction. In the case of hepatoprotective activity, CX hexane fraction showed significant improvement in terms of a biochemical liver function, antioxidative liver enzymes, and lipid peroxidation activity. Good recovery was observed in the treated hepatic tissues histologically. Hence, the results concluded that CX hexane fraction possessed prominent hepatoprotective activities which might be due to its in vitro antioxidant activity. These findings also support the use of CX as a functional food for hepatitis remedy in traditional medicinal system. PMID:25133223

Devaraj, Sutha; Ismail, Sabariah; Ramanathan, Surash

2014-01-01

76

Hepatic Stellate Cells Express Thymosin Beta 4 in Chronically Damaged Liver  

PubMed Central

Although the various biological roles of thymosin ?4 (T?4) have been studied widely, the effect of T?4 and T?4-expressing cells in the liver remains unclear. Therefore, we investigated the expression and function of T?4 in chronically damaged livers. CCl4 was injected into male mice to induce a model of chronic liver disease. Mice were sacrificed at 6 and 10 weeks after CCl4 treatment, and the livers were collected for biochemical analysis. The activated LX-2, human hepatic stellate cell (HSC) line, were transfected with T?4-specific siRNA and activation markers of HSCs were examined. Compared to HepG2, higher expression of T?4 in RNA and protein levels was detected in the activated LX-2. In addition, T?4 was up-regulated in human liver with advanced liver fibrosis. The expression of T?4 increased during mouse HSC activation. T?4 was also up-regulated and T?4-positive cells were co-localized with ?-smooth muscle actin (?-SMA) in the livers of CCl4-treated mice, whereas such cells were rarely detected in the livers of corn-oil treated mice. The suppression of T?4 in LX-2 cells by siRNA induced the down-regulation of HSC activation-related genes, tgf-?, ?-sma, collagen, and vimentin, and up-regulation of HSC inactivation markers, ppar-? and gfap. Immunofluorescent staining detected rare co-expressing cells with T?4 and ?-SMA in T?4 siRNA-transfected cells. In addition, cytoplasmic lipid droplets were observed in T?4 siRNA-treated cells. These results demonstrate that activated HSCs expressed T?4 in chronically damaged livers, and this endogenous expression of T?4 influenced HSC activation, indicating that T?4 might contribute to liver fibrosis by regulating HSC activation. PMID:25826335

Kim, Jieun; Wang, Sihyung; Hyun, Jeongeun; Choi, Steve S.; Cha, Heejae; Ock, Meesun; Jung, Youngmi

2015-01-01

77

Binge Ethanol-induced Neurodegeneration in Rat Organotypic Brain Slice Cultures: Effects of PLA2 Inhibitor Mepacrine and Docosahexaenoic Acid (DHA)  

Microsoft Academic Search

Using rat organotypic hippocampal-entorhinal cortical (HEC) slice cultures, we examined whether phospholipase A2 (PLA2) activity\\u000a is involved in binge alcohol (ethanol)-induced neurodegeneration, and whether docosahexaenoic acid (DHA; 22:6n-3), a fish\\u000a oil-enriched fatty acid that is anti-inflammatory in brain damage models, is neuroprotective. Assessed with propidium iodide\\u000a and lactate dehydrogenase (LDH) leakage, neurodamage from ethanol (6 days 100 mM ethanol with four withdrawal

James Brown; Nicholas Achille; Edward J. Neafsey; Michael A. Collins

2009-01-01

78

The antimalarial agent artesunate causes sperm DNA damage and hepatic antioxidant defense in mice.  

PubMed

Artesunate is an artemisinin derivative effective against multidrug resistant malaria. We analyzed the effects of artesunate 40mg/kg b.w. as a single dose (ART1) or 13.3mg/kg b.w. for 3 days at 24h intervals (ART2) on mice spermatozoa at morphological and molecular level, and hepatic antioxidant status following 24h and 35 days following exposures in vivo. Artesunate significantly reduced epididymal sperm count and increased the frequency of sperms with abnormal head morphology following 24h of exposure. Comet assay analysis revealed significant increase in DNA strand breaks in spermatozoa evidenced by about 3-fold increase in comet tail DNA and up to 10-fold increase in Olive tail moment following 35 days of artesunate treatment. The damage index was significantly higher in the treated groups (40.27±6.62 and 37.07±5.35 for ART1 and ART2 respectively) as compared to the control group (16.13±3.21) indicating the genotoxic effect of artesunate. The significant reduction in GSH, SOD and increase in lipid peroxidation indicate involvement of oxidative mechanisms in artesunate induced toxicity in mice. The present study suggests that artesunate has the potential to breach the testis-blood barrier and cause toxicity to male germ cells which may have implications in male reproductive toxicity. PMID:25726169

Singh, Supriya; Giri, Anirudha; Giri, Sarbani

2015-01-01

79

Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice  

PubMed Central

Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 ?g/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions. PMID:25284923

Kang, H.; Koppula, S.

2014-01-01

80

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.  

PubMed

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-? were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-? and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT. PMID:25004996

Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

2014-11-01

81

Early maternal separation affects ethanol-induced conditioning in a nor-BNI insensitive manner, but does not alter ethanol-induced locomotor activity.  

PubMed

Early environmental stress significantly affects the development of offspring. This stress has been modeled in rats through the maternal separation (MS) paradigm, which alters the functioning of the HPA axis and can enhance ethanol intake at adulthood. Infant rats are sensitive to ethanol's reinforcing effects, which modulate ethanol seeking and intake. Little is known about the impact of MS on sensitivity to ethanol's appetitive and aversive effects during infancy. The present study assessed ethanol-induced conditioned place preference established through second-order conditioning (SOC), spontaneous or ethanol-induced locomotor activity and ethanol intake in preweanling rats that experienced normal animal facility rearing (AFR) or daily episodes of maternal separation (MS) during postnatal days 1-13 (PDs 1-13). Low-ethanol dose (0.5 g/kg) induced appetitive conditioned place preference (via SOC) in control rats given conventional rearing but not in rats given maternal separation in early infancy, whereas 2.0 g/kg ethanol induced aversive conditioned place preference in the former but not the latter. The administration of a kappa antagonist at PD 1 or immediately before testing did not alter ethanol-induced reinforcement. High (i.e., 2.5 and 2.0 g/kg) but not low (i.e., 0.5 g/kg) ethanol dose induced reliable motor stimulation, which was independent of early maternal separation. Ethanol intake and blood alcohol levels during conditioning were unaffected by rearing conditions. Pups given early maternal separation had lower body weights than controls and showed an altered pattern of exploration when placed in an open field. These results indicate that, when assessed in infant rats, earlier maternal separation alters the balance between the appetitive and aversive motivational effects of ethanol but has no effect on the motor activating effects of the drug. PMID:22108648

Pautassi, Ricardo Marcos; Nizhnikov, Michael E; Fabio, Ma Carolina; Spear, Norman E

2012-01-01

82

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. PMID:24944771

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

2014-01-01

83

Matcha, a powdered green tea, ameliorates the progression of renal and hepatic damage in type 2 diabetic OLETF rats.  

PubMed

Matcha, a powdered green tea produced by grinding with a stone mill, has been popularly used in the traditional tea ceremony and foods in Japan. Matcha is well known to be richer in some nutritional elements and epigallocatechin 3-O-gallate than other green teas. In our previous study, epigallocatechin 3-O-gallate exhibited protective effects against renal damage in a rat model of diabetic nephropathy. In the present study, we investigated the preventive effects of Matcha (50, 100, or 200 mg/kg/day) on the progression of hepatic and renal damage in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats were orally administered Matcha for 16 weeks, and we assessed biochemical parameters in the serum, liver, and kidney and expression levels of major products of advanced glycation end products (AGEs), N(6)-(carboxylmethyl)lysine (CML) and N(6)-(carboxylethyl)lysine (CEL), receptor for AGE (RAGE), and sterol regulatory element binding proteins (SREBPs)-1 and -2. Serum total protein levels were significantly increased by Matcha administration, whereas the serum albumin and glycosylated protein levels as well as the renal glucose and triglyceride levels were only slightly or not at all affected. However, Matcha treatment significantly lowered the glucose, triglyceride, and total cholesterol levels in the serum and liver, renal AGE levels, and the serum thiobarbituric acid-reactive substances levels. In addition, Matcha supplementation resulted in decreases in the renal CML, CEL, and RAGE expressions as well as an increase in hepatic SREBP-2 expression, but not that of SREBP-1. These results suggest that Matcha protects against hepatic and renal damage through the suppression of renal AGE accumulation, by decreases in hepatic glucose, triglyceride, and total cholesterol levels, and by its antioxidant activities. PMID:19735169

Yamabe, Noriko; Kang, Ki Sung; Hur, Jong Moon; Yokozawa, Takako

2009-08-01

84

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

85

Effect of Ribavirin Alone or Combined with Silymarin on Carbon Tetrachloride Induced Hepatic Damage in Rats  

PubMed Central

The effect of the antiviral agent ribavirin given alone or in combination with silymarin on the development of liver injury induced in rats with carbon tetrachloride (CCl4; 2.8 ml/kg followed by 1.4 ml/kg after one week) was studied. Ribavirin at three dose levels (30, 60 or 90 mg/kg), silymarin (25 mg/kg) or combination of ribavirin (60 mg/kg) and silymarin (25 mg/kg) was administered once daily orally for 14 days, starting at time of administration of CCl4. The administration of ribavirin decreased the elevations in serum alanine aminotransferase (ALT) by 78.5, 82.1, 75.1%, aspartate aminotransferase (AST) 47.5, 37.4, 38.8%, and alkaline phosphatase (ALP) by 23.4, 16, 21.6%, respectively and also pre-vented the development of hepatic necrosis caused by CCl4. In comparison, the elevated serum ALT, AST and ALP levels decreased to 43.3%, 46%, and 37.5% of controls, respectively by silymarin. When silymarin was combined with ribavirin, the serum activities of AST and ALP were further decreased, indicating a beneficial additive effect. Morphometric analysis indicated significant reduction in the area of necrosis and fibrosis on ribavirin treatment and this was further reduced after the addition of silymarin. Metabolic pertuberations caused by CCl4 as reflected in a decrease in intracellular protein content in hepatocytes were improved by ribavirin monotherapy and to higher extent by combined silymarin and ribavirin therapy. Proliferating cell nuclear antigen was reduced in nuclei of hepatocytes by ribavirin montherapy or the combination of ribavirin and silymarin compared with CCl4-control group. The study demonstrates that ribavirin treatment in the model of CCl4-induced liver injury results in less liver damage. Results also indicate that the combined application of ribavirin and sily-marin is likely to be a useful additive in reducing liver injury. PMID:21901059

Salam, Omar M.E. Abdel; Sleem, Amany A.; Omara, Enayat A.; Hassan, Nabila S.

2007-01-01

86

Olea europaea Linn. Fruit Pulp Extract Protects against Carbon Tetrachloride-induced Hepatic Damage in Mice  

PubMed Central

The present study we investigated the hepatoprotective effects of Olea europaea fruit pulp extract against carbon tetrachloride-induced hepatic damage in experimental mice. Further we explored the antioxidant potential of the extract to substantiate the hepatoprotective properties. Biochemical parameters were analyzed in the serum of experimental mice using respective diagnostic kits. Antioxidant activities were measured following alkyl and hydroxyl radical scavenging assays. Compared with control groups, administration of the extract to carbon tetrachloride-treated mice significantly reduced the elevated serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. The carbon tetrachloride-treated morphological changes in hepatocyte architecture were also reversed by extract pretreatment. Further, the carbon tetrachloride-treated increased serum cholesterol levels such as triglyceride and low density/very low-density lipoprotein in the liver were reversed in acute and chronic carbon tetrachloride-treated mice. The extract was also found to significantly increase the serum level of high-density lipoproteins in carbon tetrachloride-treated mice. Furthermore, the extract showed significant in vitro antioxidant actions by scavenging the alkyl and hydroxyl free radicals, substantiating its use in hepatoprotection. The concentration of the extract necessary for 50% inhibition of alkyl and hydroxyl radicals was 72.41 and 52.24 ?g/ml, respectively. In conclusion, data from our study suggest that Olea europaea fruit pulp extract could prevent carbon tetrachloride-treated acute and chronic liver degeneration and attenuated the lipid levels elevated by carbon tetrachloride. The hepatoprotective activity exhibited by Olea europaea extract might possibly be through its antioxidant defense mechanisms. PMID:25284924

Kang, H.; Koppula, S.

2014-01-01

87

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. PMID:22203864

Saoudi, Mongi; El Feki, Abdelfattah

2012-01-01

88

Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1  

PubMed Central

Background and Aims Hepatitis C virus (HCV)-induced chronic inflammation may induce oxidative stress which could compromise the repair of damaged DNA, rendering cells more susceptible to spontaneous or mutagen-induced alterations, the underlying cause of liver cirrhosis and hepatocellular carcinoma. In the current study we examined the induction of reactive oxygen species (ROS) resulting from HCV infection and evaluated its effect on the host DNA damage and repair machinery. Methods HCV infected human hepatoma cells were analyzed to determine (i) ROS, (ii) 8-oxoG and (iii) DNA glycosylases NEIL1, NEIL2, OGG1. Liver biopsies were analyzed for NEIL1. Results Human hepatoma cells infected with HCV JFH-1 showed 30–60-fold increases in ROS levels compared to uninfected cells. Levels of the oxidatively modified guanosine base 8-oxoguanine (8-oxoG) were significantly increased sixfold in the HCV-infected cells. Because DNA glycosylases are the enzymes that remove oxidized nucleotides, their expression in HCV-infected cells was analyzed. NEIL1 but not OGG1 or NEIL2 gene expression was impaired in HCV-infected cells. In accordance, we found reduced glycosylase (NEIL1-specific) activity in HCV-infected cells. The antioxidant N-acetyl cystein (NAC) efficiently reversed the NEIL1 repression by inhibiting ROS induction by HCV. NEIL1 expression was also partly restored when virus-infected cells were treated with interferon (IFN). HCV core and to a lesser extent NS3-4a and NS5A induced ROS, and downregulated NEIL1 expression. Liver biopsy specimens showed significant impairment of NEIL1 levels in HCV-infected patients with advanced liver disease compared to patients with no disease. Conclusion Collectively, the data indicate that HCV induction of ROS and perturbation of NEIL1 expression may be mechanistically involved in progression of liver disease and suggest that antioxidant and antiviral therapies can reverse these deleterious effects of HCV in part by restoring function of the DNA repair enzyme/s. PMID:20074151

Pal, Sampa; Polyak, Stephen J; Bano, Nazneen; Qiu, Wan Chong; Carithers, Robert L; Shuhart, Margaret; Gretch, David R; Das, Aditi

2013-01-01

89

Modification of ethanol-induced motor impairment by diet, diuretic, mineralocorticoid, or prostaglandin synthetase inhibitor  

Microsoft Academic Search

Ethanol-induced motor impairment in rats was measured following a number of different dietary or drug treatments. A low sodium diet combined with injections of the diuretic furosemide, but not a low sodium diet alone, increased motor impairment while a high sodium diet decreased impairment. Blood ethanol measurements indicated that both effects were probably mediated by changes in blood ethanol levels.

L. A. Grupp; J. Elias; E. Perlanski; R. B. Stewart

1985-01-01

90

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

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

Effect of dietary epigallocatechin-3-gallate on cytochrome P450 2E1-dependent alcoholic liver damage: enhancement of fatty acid oxidation.  

PubMed

This study was designed to determine whether dietary epigallocatechin-3-gallate (EGCG), the most abundant catechin polyphenol in green tea, can protect the liver from cytochrome P450 2E1 (CYP2E1)-dependent alcoholic liver damage. Compared with an ethanol group, when EGCG was present in the ethanol diet, the formation of a fatty liver was significantly reduced and the serum aspartate transaminase (AST) and alanine transaminase (ALT) levels were much lower. Ethanol treatment significantly elevated hepatic CYP2E1 expression while simultaneously reducing hepatic phospho-acetyl CoA carboxylase (p-ACC) and carnitine palmitoyl-transferase 1 (CPT-1) levels. While EGCG markedly reversed the effect of ethanol on hepatic p-ACC and CPT-1 levels, it had no effect on the ethanol-induced elevation in CYP2E1 expression. EGCG prevents ethanol-induced hepatotoxicity and inhibits the development of a fatty liver. These effects were associated with improvements in p-ACC and CPT-1 levels. The use of EGCG might be useful in treating patients with an alcoholic fatty liver. PMID:18071271

Yun, Jun-Won; Kim, Young-Kyung; Lee, Byoung-Seok; Kim, Chae-Wook; Hyun, Jin-Sook; Baik, Joo-Hyun; Kim, Jung-Ju; Kim, Bae-Hwan

2007-12-01

93

Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver.  

PubMed

The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats. PMID:17258234

Kasdallah-Grissa, Abir; Mornagui, Bessem; Aouani, Ezzedine; Hammami, Mohamed; El May, Michelle; Gharbi, Najoua; Kamoun, Abdelaziz; El-Fazaâ, Saloua

2007-02-20

94

Aripiprazole an atypical antipsychotic protects against ethanol induced gastric ulcers in rats  

PubMed Central

The present investigation was undertaken, to study the gastro-protective potential of aripiprazole (ARI) an atypical antipsychotic drug in ethanol induced gastric ulcers in rats. ARI (10, 30, 100 mg/kg) was tested for gastric secretion and antiulcer activity in different groups of male Sprague Dawley rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryls (NP-SH), myeloperoxidase (MPO), and serotonin were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ethanol resulted in gastric mucosal injury and a high index of ulcer. Pretreatment with ARI significantly (P < 0.001), reduced the gastric lesions induced by ethanol and also resulted in a significant decrease in the gastric secretion, and total acidity in pylorus ligated rats. ARI also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P < 0.001). The histological changes and the increased MDA and MPO activity were also significantly (P < 0.001) inhibited by ARI. Ethanol induced depletion in the levels of serotonin in the gastric tissue were also significantly restored by pretreatment with ARI (p < 0.001). ARI showed significant antiulcer and gastroprotective activity against ethanol induced gastric ulcers. The gastroprotective effects of ARI may be due to its anti-secretory, antioxidant and anti-inflammatory action and also due to the restoration of the depleted gastric serotonin levels. PMID:25232384

Asmari, Abdulrahman Al; Arshaduddin, Mohammed; Elfaki, Ibrahim; Kadasah, Saeed; Robayan, Abdulrahman Al; Asmary, Saeed Al

2014-01-01

95

Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study  

PubMed Central

Background Peroxisome proliferators-activated receptor alpha (PPAR?) activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPAR? agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis. Methods Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL), III = BDL + vehicle (gum Arabic), IV = BDL + fenofibrate (100 mg/kg/day). All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), gamma-glutamyl transferase, (GGT), tumor necrosis factor alpha (TNF-?), interleukin 1 beta (IL-1 ?), and total bile acid (TBA) in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining. Results Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-?, IL-1 ? levels, and TBA (P < 0.01). Hepatic portal inflammation, hepatic necrosis, number of the bile ducts and apoptosis in rats with BDL were more prominent than the sham-operated animals (P < 0.01). PPAR? induction improved all histopathologic parameters (P < 0.01), except for the number of the bile duct, which was markedly increased by fenofibrate therapy (P < 0.01). Conclusion Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis. PMID:18045488

Cindoruk, Mehmet; Kerem, Mustafa; Karakan, Tarkan; Salman, Bulent; Akin, Okan; Alper, Murat; Erdem, Ozlem; Ünal, Selahattin

2007-01-01

96

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

97

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

98

Role of CYP2E1 in Ethanol-Induced Oxidant Stress, Fatty Liver and Hepatotoxicity  

PubMed Central

Background/Aims Several pathways contribute to mechanisms by which ethanol induces oxidant stress. While some studies support a role for cytochrome P450 2E1 (CYP2E1), others do not. There is a need to develop oral models of significant ethanol-induced liver injury and to evaluate the possible role of CYP2E1 in ethanol actions in such models. Methods We evaluated chronic ethanol-induced liver injury, steatosis and oxidant stress in wild-type (WT) mice, CYP2E1 knockout (KO) mice and in humanized CYP2E1 knockin (KI) mice, where the human 2E1 was added back to mice deficient in the mouse 2E1. WT mice and CYP2E1 KO and KI mice (both provided by Dr. F. Gonzalez, NCI) were fed a high-fat Lieber-DeCarli liquid diet for 3 weeks; pair-fed controls received dextrose. Results Ethanol produced fatty liver and oxidant stress in WT mice, but liver injury (transaminases, histopathology) was minimal. Ethanol-induced steatosis and oxidant stress were blunted in the KO mice (no liver injury) but restored in the KI mice. Significant liver injury was produced in the ethanol-fed KI mice with elevated transaminases and necrosis. This liver injury in the KI mice was associated with elevated oxidant stress and elevated levels of the human CYP2E1 compared to levels of the mouse 2E1 in WT mice. Activation of JNK was observed in the ethanol-fed KI mice compared to the other groups. Fatty liver in WT and KI mice was associated with lower levels of lipolytic PPAR-?. No such changes were found in the ethanol-fed KO mice. Conclusions These results show that CYP2E1 plays a major role in ethanol-induced fatty liver and oxidant stress. Restoring CYP2E1 in the CYP2E1 KO mice restores ethanol-induced fatty liver and oxidant stress. PMID:21525766

Cederbaum, Arthur I.

2011-01-01

99

Genetic differences in ethanol-induced hyperglycemia and conditioned taste aversion  

SciTech Connect

Genetic differences in the hyperglycemic response to acute ethanol exposure and ethanol-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J and DBA/2J mice were injected with ethanol and blood glucose levels determined over 4 h. C57 mice demonstrated greater dose-dependent elevations in blood glucose compared to DBA mice. In a conditioned taste aversion procedure, water deprived mice received ethanol injections immediately after access to a NaCl flavored solution. DBA mice developed aversion to the ethanol-paired flavor at a lower dose than C57 mice. These results provide further support for a possible inverse genetic relationship between sensitivity to ethanol-induced hyperglycemia and sensitivity to conditioned taste aversion.

Risinger, F.O.; Cunningham, C.L. (Oregon Health Science Univ., Portland (United States))

1992-01-01

100

Gastroprotective activity and mechanism of novel dichlorido-zinc(II)-4-(2-(5-methoxybenzylideneamino)ethyl)piperazin-1-iumphenolate complex on ethanol-induced gastric ulceration.  

PubMed

Zinc complexes were reported to have anti-ulcer activity and used as drug for the treatment of gastrointestinal disorders. A novel compound dichlorido-zinc(II)-4-(2-(5-methoxybenzylidene amino)ethyl)piperazin-1-iumphenolate (ZnHMS) was synthesized, characterized and evaluated for its gastroprotective activity against ethanol-induced ulcer in rats. Gross and microscopic lesions, histochemical staining of glycogen storage, biochemical and immunological parameters were taken into consideration. Oral administration of ZnHMS (30 and 60 mg/kg; 14 days) dose-dependently inhibited gastric lesions. It significantly increased the mucus content and total acidity compared to the control group (P<0.01). Serum levels of aspartate (AST), alanine (ALT) transaminases, pro-inflammatory interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?) and anti-inflammatory interleukin-10 (IL-10) in the rats exposed to ethanol induced ulceration have been altered. ZnHMS considerably enhances (P<0.05) the protection of gastric epithelia by modulating the acute alterations of AST, ALT, IL-6, IL-10, TNF-? and stomach glycogen. Interestingly, ZnHMS did interfere with the natural release of nitric oxide. In addition, acute toxicity study revealed no abnormal sign to the rats treated with ZnHMS (2000 mg/kg). These findings suggest that the gastroprotective activity of ZnHMS might contribute in adjusting the inflammatory cytokine-mediated oxidative damage to the gastric mucosa. PMID:22178775

Salga, Muhammad Saleh; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Abdelwahab, Siddig Ibrahim

2012-01-25

101

Evaluation of the gastroprotective effect of Laurus nobilis seeds on ethanol induced gastric ulcer in rats  

Microsoft Academic Search

The possible antiulcerogenic activity of Laurus nobilis seeds was tested on experimentally (ethanol) induced gastric ulcer in rats. The results indicated antiulcerogenic activity for 20 and 40% aqueous extracts as well as for the oily fraction of these seeds. In acute toxicity studies, the aqueous extract was found safe with LD50 compared to oil LD50 0.33 ml\\/kg body weight.

F. U Afifi; E Khalil; S. O Tamimi; A Disi

1997-01-01

102

Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.  

PubMed

Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. PMID:21803053

Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

2011-12-01

103

Ethanol-induced increase in portal blood glow: Role of adenosine  

SciTech Connect

The mechanism by which ethanol induces an increase in portal vein blood flow was studied in rats using radiolabeled microspheres. Ethanol by gavage resulted in an increase of 50-70% in portal vein blood flow. The ethanol-induced increase in portal blood flow was suppressed by the adenosine receptor blocker 8-phenyltheophylline. By itself, 8-phenyltheophylline was without effect on cardiac output or portal blood flow. Adenosine infusion resulted in a dose-dependent increase in portal blood flow. This adenosine-induced increase in portal blood flow was inhibited by 8-phenyltheophylline in a dose-dependent manner. Both alcohol and adenosine significantly reduced preportal vascular resistance by 40% and 60%, respectively. These effects were fully suppressed by 8-phenyltheophylline. It is concluded that adenosine is a likely candidate to mediate the ethanol-induced increase in portal vein blood flow. It is suggested that an increase in circulating acetate and liver hypoxia may mediate the effects of alcohol by increasing tissue and interstitial adenosine levels.

Orrego, H.; Carmichael, F.J.; Saldivia, V.; Giles, H.G.; Sandrin, S.; Israel, Y. (Univ. of Toronto, Ontario (Canada))

1988-04-01

104

Role of neutrophilic elastase in ethanol induced injury to the gastric mucosa  

SciTech Connect

Intragastric administration of ethanol (at concentrations likely to be encountered by the mucosa during acute intoxication) produces gastritis. Recent studies have implicated neutrophils in the gastric mucosal injury induced by luminal ethanol. The objective of the present study was to assess whether neutrophilic elastase contributes to the ethanol-induced gastric mucosal injury. Sprague-Dawley rats were instrumented for perfusion of the gastric lumen with saline or ethanol. Mucosal injury was quantitated by continuously measuring the blood-to-lumen clearance of {sup 51}Cr-EDTA. The experimental protocol consisted of a 40 minute control period (saline perfusion) followed by three successive 40 minute experimental periods (ethanol perfusion). During the three experimental periods the concentration of ethanol was progressively increased to 10, 20, and 30%. The experiments were performed in untreated animals and in animals pretreated with either Eglin c (an inhibitor of elastase and cathepsin G activity) or L 658 (a specific inhibitor of elastase activity). The effects of ethanol on EDTA clearance (x control) in untreated (n = 9) and L658 treated (n = 5) animals are shown in the Table below. Pretreatment with L 658 significantly attenuated the ethanol-induced increases in EDTA clearance. Pretreatment with Eglin c (n = 6) also provided some protection against ethanol-induced injury, but not to the extent as that provided by L658. The results of the authors studies suggest that neutrophilic elastase contributes to a gastric mucosal injury induced by luminal perfusion of the stomach with physiologically relevant concentrations of ethanol.

Kvietys, P.R.; Carter, P.R. (Louisiana State Univ. Medical Center, Shreveport (United States))

1990-02-26

105

Characterization of an ethanol-inducible promoter system in Catharanthus roseus hairy roots.  

PubMed

Efforts to engineer Catharanthus roseus hairy roots to produce commercially significant amounts of valuable compounds, such as the terpenoid indole alkaloids vinblastine and vincristine, require the development of tools to study the effects of overexpressing key metabolic and regulatory genes. The use of inducible promoters allows researchers to control the timing and level of expression of genes of interest. In addition, use of inducible promoters allows researchers to use a single transgenic line as both the control and experimental line, minimizing the problems associated with clonal variation. We have previously characterized the use of a glucocorticoid-inducible promoter system to study the effects of gene overexpression within the terpenoid indole alkaloid pathway on metabolite production. Here the feasibility of using an ethanol-inducible promoter within C. roseus hairy roots is reported. This ethanol-inducible promoter is highly sensitive to ethanol concentration with a concentration of 0.005% ethanol causing a 6-fold increase in CAT reporter activity after 24 h of induction. The ethanol-inducible CAT activity increased 24-fold over a 72-h induction period with 0.5% ethanol. PMID:17715939

Peebles, Christie A M; Gibson, Susan I; Shanks, Jacqueline V; San, Ka-Yiu

2007-01-01

106

Ethanol-induced loss of brain cyclic AMP binding proteins: correlation with growth suppression  

SciTech Connect

Brain hypoplasia secondary to maternal ethanol consumption is a common fetal defect observed in all models of fetal alcohol syndrome. The molecular mechanism by which ethanol inhibits growth is unknown but has been hypothesized to involve ethanol-induced changes in the activity of cyclic-AMP stimulated protein kinase. Acute and chronic alcohol exposure elevate cyclic AMP level in many tissues, including brain. This increase in cyclic AMP should increase the phosphorylating activity of kinase by increasing the amount of dissociated (active) kinase catalytic subunit. In 7-day embryonic chick brains, ethanol-induced growth suppression was correlated with increased brain cyclic AMP content but neither basal nor cyclic AMP stimulated kinase catalytic activity was increased. However, the levels of cyclic AMP binding protein (kinase regulatory subunit) were significantly lowered by ethanol exposure. Measured as either /sup 3/H cyclic AMP binding or as 8-azido cyclic AM/sup 32/P labeling, ethanol-exposed brains had significantly less cyclic AMP binding activity (51 +/- 14 versus 29 +/- 10 units/..mu..g protein for 8-azido cyclic AMP binding). These findings suggest that ethanol's effect on kinase activity may involve more than ethanol-induced activation of adenylate cyclase.

Pennington, S.; Kalmus, G.

1987-05-01

107

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. PMID:23365597

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

2012-01-01

108

Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats  

PubMed Central

The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20?mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500?mg/kg) and the experimental groups (62.5, 125, 250, and 500?mg/kg). After 1?h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1?h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5?g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions. PMID:23781513

Hassandarvish, Pouya; Abdul Majid, Nazia; Hadi, A. Hamid A.; Nordin, Noraziah; Abdulla, Mahmood A.

2013-01-01

109

Resveratrol mitigate structural changes and hepatic stellate cell activation in N'-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage.  

PubMed

Resveratrol, a polyphenol, found in skin of red grapes, peanuts and berries possesses anti-inflammatory, anti-carcinogenic and lipid modulation properties. Here, we demonstrate in vivo antifibrotic activity of resveratrol in a mammalian model, wherein hepatic fibrosis was induced by N'-nitrosodimethylamine (NDMA) administration. Apart from being a potent hepatotoxin, NDMA is a known mutagen and carcinogen, as well. To induce hepatic fibrosis, rats were administered NDMA (i.p.) in 10mg/kgb.wt thrice/week for 21 days. Another group of animals received resveratrol supplement (10mg/kgb.wt) subsequent to NDMA administration and were sacrificed weekly. The changes in selected biomarkers were monitored to compare profibrotic effects of NDMA and antifibrotic activity of resveratrol. The selected biomarkers were: sera transaminases, ALP, bilirubin, liver glycogen, LPO, SOD, protein carbonyl content, ATPases (Ca(2+), Mg(2+), Na(+)/K(+)) and hydroxyproline/collagen content. Alterations in liver architecture were assessed by H&E, Masson's trichrome and reticulin staining of liver biopsies. Immuno-histochemistry and immunoblotting were employed to examine expression of ?-SMA. Our results demonstrate that during NDMA-induced liver fibrosis transaminases, ALP, bilirubin, hydroxyproline and liver collagen increases, while liver glycogen is depleted. The decline in SOD (>65%) and ATPases, which were concomitant with the elevation in MDA and protein carbonyls, strongly indicate oxidative damage. Fibrotic transformation of liver in NDMA-treated rats was verified by histopathology, immuno-histochemistry and immunoblotting data, with the higher expressivity of ?-SMA-positive HSCs being most established diagnostic immuno-histochemical marker of HSCs. Resveratrol-supplement refurbished liver architecture by significantly restoring levels of biomarkers of oxidative damage (MDA, SOD, protein carbonyls and membrane-bound ATPases). Therefore, we conclude that antifibrotic effect of resveratrol is due to restrained oxidative damage and down-regulation of ?-SMA, which inhibits HSC activation to obstruct liver fibrosis. PMID:25064540

Ahmad, Areeba; Ahmad, Riaz

2014-09-25

110

Suramin inhibits hepatic tissue damage in hepatocellular carcinoma through deactivation of heparanase enzyme.  

PubMed

Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapy, and is rarely amenable to radiotherapy. Heparanase, enzyme attacks heparan sulfate proteoglycans (HSPGs), is preferentially expressed in human tumors and its overexpression in low-metastatic tumor confers a highly invasive phenotype in experimental animals. Meanwhile, high doses of suramin dramatically increase tissue glycosaminoglycans due, in part, to inhibition of heparanase enzymes. Therefore, the following study was conducted to evaluate the chemopreventive and hepatoprotective effects of suramin in in-vivo model of HCC. Therefore, HCC was induced in SD rats by thioacetamide (200mg/kg) in presence/absence of suramin (20mg/kg). Liver impairment was assessed by measuring serum ?-fetoprotein and investigating liver sections stained with Hematoxylin/Eosin. Hepatic HSPGs and heparanse were measured by ELISA. Glucosamine and glucuronic acid were measured by chemical methods. Gene expression of fibroblast growth factor (FGF)-2 and caspase-3 was measured. Apoptotic pathway was evaluated by measuring the activity of caspase-3/8/9. Suramin increased the animal survival and decreased serum ?-fetoprotein. In addition, suramin ameliorated fibrosis and massive hepatic tissue breakdown. Suramin restored hepatic HSPGs and reduced the activity of hepatic heparanase leading to decreased hepatic levels of glucosamine and glucuronic acid. Moreover, suramin reduced the gene expression of FGF-2 and caspase-3. Finally, suramin blocked the elevated activity of caspase-3/8/9. In conclusion, surmain showed antitumor activity as well as hepatoprotective effects. Besides its antioxidant activity, other mechanisms are involved including restoration of HSPGs and inhibition of heparanase and FGF-2. Suramin inhibits intrinsic and extrinsic apoptotic pathway. Targeting HSPGs expression is potential therapeutic target for HCC. PMID:24530413

Tayel, Ahmed; Abd El Galil, Khaled H; Ebrahim, Mohamed A; Ibrahim, Ahmed S; El-Gayar, Amal M; Al-Gayyar, Mohammed M H

2014-04-01

111

Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat.  

PubMed

The present study was undertaken to determine whether subacute treatment with aqueous extract of carob (Ceratonia siliqua L.) pods (AECPs) protects against ethanol (EtOH)-induced oxidative stress in rat liver. Animals were divided into four groups: control, carob, EtOH and EtOH + carob. Wistar rats were intraperitoneally pretreated with AECP (600 mg/kg body weight (bw)) during 7 days and intoxicated for 6 h by acute oral administration of EtOH (6 g/kg bw) 24 h after the last injection. We found that acute administration of EtOH leads to hepatotoxicity as monitored by the increase in the levels of hepatic marker aspartate aminotransferase and alanine aminotransferase as well as hepatic tissue injury. EtOH also increased the formation of malondialdehyde in the liver, indicating an increase in lipid peroxidation and depletion of antioxidant enzyme activities as superoxide dismutase, catalase and glutathione peroxidase. Subacute carob pretreatment prevented all the alterations induced by EtOH and returned their levels to near normal. Importantly, we showed that acute alcohol increased hepatic and plasmatic hydrogen peroxide and free iron levels. The carob pretreatment reversed EtOH effects to near control levels. These data suggest that carob could have a beneficial effect in inhibiting the oxidative damage induced by acute EtOH administration and that its mode of action may involve an opposite effect on plasma and tissue-free iron accumulation. Indeed, carob can be offered as a food additive to protect against EtOH-induced oxidative damage. PMID:23363576

Souli, Abdellaziz; Sebai, Hichem; Chehimi, Latifa; Rtibi, Kaïs; Tounsi, Haifa; Boubaker, Samir; Sakly, Mohsen; El-Benna, Jamel; Amri, Mohamed

2013-01-30

112

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. PMID:24363821

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

2013-01-01

113

Tacrine, an Oral Acetylcholinesterase Inhibitor, Induced Hepatic Oxidative Damage, Which Was Blocked by Liquiritigenin through GSK3-beta Inhibition.  

PubMed

Although the cholinesterase inhibitor tacrine has been successfully used for the treatment of Alzheimer's disease, it is known to have hepatotoxic effects. Liquiritigenin (LQ), an active flavonoid in Glycyrrhizae radix, exerts protective effects against liver damage. This study investigated the toxic effect of tacrine on hepatocytes and the beneficial effect of LQ on tacrine intoxication in vivo and in vitro, and the underlying mechanism involved. In hepatocyte cell lines, tacrine induced cell death and oxidative stress, as indicated by decreases in cell viability and glutathione (GSH) contents, which were blocked by pretreatment with LQ. Fluorescent activated cell sorter (FACS) analysis revealed that LQ inhibited cellular H2O2 production and mitochondrial dysfunction induced by tacrine in HepG2 cells. Furthermore, LQ promoted inhibitory phosphorylation of glycogen synthase kinase-3? (GSK3?) and prevented decreases in GSK3? phosphorylation induced by tacrine. In rats treatment with tacrine at 30?mg/kg increased hepatic damage as assessed by blood biochemistry and histopathology. Administration of LQ (10 or 30?mg/kg/d, per os (p.o.)) or the hepatoprotective drug sylimarin (100?mg/kg/d) for 3?d inhibited elevations in alanine aminotransferase, aspartate aminotransferase, and histological changes induced by tacrine. These results show that LQ efficaciously protects the rat liver against tacrine-induced liver damage, and suggest that LQ is a therapeutic candidate for ameliorating the hepatotoxic effects of tacrine. PMID:25747977

Park, Sang Mi; Ki, Sung Hwan; Han, Nu Ri; Cho, Il Je; Ku, Sae Kwang; Kim, Sang Chan; Zhao, Rong Jie; Kim, Young Woo

2015-01-01

114

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

115

[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

116

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

117

Protective effects of friedelin isolated from Azima tetracantha Lam. against ethanol-induced gastric ulcer in rats and possible underlying mechanisms.  

PubMed

The current study was aimed to investigate the gastroprotective effects of friedelin isolated from the hexane extract of leaves of Azima tetracantha. Ethanol-induced gastric ulcer model was used to investigate the gastroprotective effects of friedelin. Antioxidant enzymes, lipid peroxidation, nitric oxide, gastric vascular permeability, pro and anti-inflammatory cytokines and apoptosis level have been investigated. Ethanol caused severe gastric damage and friedelin pretreatment protected against its deleterious role. Antioxidant enzyme activities, anti-inflammatory cytokines, prostaglandin E2 (PGE2), constitutive nitric oxide synthase (cNOS) and mucus weight have been increased significantly. However, the vascular permeability, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), caspase-3 and apoptosis level have significantly been decreased after friedelin ingestion. The present study has clearly demonstrated the anti-ulcer potential of friedelin, these findings suggested that friedelin could be a new useful natural gastroprotective tool against gastric ulcer. PMID:25617794

Antonisamy, Paulrayer; Duraipandiyan, Veeramuthu; Aravinthan, Adithan; Al-Dhabi, Naif Abdullah; Ignacimuthu, Savarimuthu; Choi, Ki Choon; Kim, Jong-Hoon

2015-03-01

118

Gastroprotective effect of crocin in ethanol-induced gastric injury in rats.  

PubMed

The present study investigated the gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Rats were allocated into a normal group, an ulcer group, a crocin-treated group, an ulcer group pretreated with crocin, and an ulcer group pretreated with omeprazole as a reference anti-ulcer drug. Rats were sacrificed 3h after ethanol administration. Prophylactic administration of crocin (50mg/kg/day, i.p.) for 3 consecutive days before the administration of 70% ethanol (10ml/kg, orally) resulted in significant gastroprotection compared to ethanol-ulcerated rats as manifested by significant reduction in the gastric ulcer index. Crocin pretreatment increased ethanol-lowered levels of gastric juice mucin and mucosal prostaglandin E2 (PGE2) and interleukin-6 (IL-6). Moreover, crocin significantly decreased ethanol-elevated tumor necrosis factor-alpha (TNF-?) level, myeloperoxidase activity and heat shock protein 70 mRNA and protein levels. It also restored ethanol-altered mucosal levels of glutathione, malondialdehyde and superoxide dismutase activity. Furthermore, crocin-pretreatment alleviated ethanol-induced mucosal apoptosis as revealed by significant down-regulation of cytochrome c and caspase-3 mRNA expression, significant decrease in caspase-3 activity and mitigated DNA fragmentation as indicated by significant decrements in comet parameters. The protective efficacy of crocin was further supported by histological assessment. No significant difference was observed between crocin and omeprazole (20mg/kg orally 1h before ethanol administration) regarding their mucin-secretagogue and antioxidant effects, as well as their effects on TNF-?, IL-6 and cytochrome c. On the other hand, omeprazole was superior in enhancing PGE2 level and in alleviating neutrophil infiltration, caspase-3 activation and DNA fragmentation. Conclusively, crocin protects rat gastric mucosa against ethanol-induced injury via anti-inflammatory, anti-oxidative, anti-apoptotic and mucin-secretagogue mechanisms that are probably mediated by enhanced PGE2 release. PMID:25637687

El-Maraghy, Shohda A; Rizk, Sherine M; Shahin, Nancy N

2015-03-01

119

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

120

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...

121

A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury.  

PubMed

The multitarget iron chelator, M30, is a novel antioxidant and protective agent against oxidative stress in a spectrum of diseases. However, there is no report regarding its role in liver diseases. Since oxidative stress is one of the major pathological events during the progression of alcoholic liver diseases, the protective effects and mechanisms of M30 on ethanol-induced hepatocyte injury were investigated in this study. Rat hepatocyte line BRL-3A was pretreated with M30 prior to ethanol treatment. Cell death, apoptosis, oxidative stress, and inflammation were examined. Specific antagonists and agonists were applied to determine the involvements of hypoxia inducible factor-1 alpha (HIF-1?) and its upstream adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1?/NOD-like receptor 3 (NLRP3) inflammasome pathway. We found that M30 significantly attenuated ethanol-induced cellular death, apoptosis, production of reactive oxygen species (ROS), and secretion of inflammatory cytokines and inhibited activation of the AC/cAMP/PKA/HIF-1?/NLRP3 inflammasome pathway. Inhibition and activation of the AC/cAMP/PKA/HIF-1? pathway mimicked and abolished the effects of M30, respectively. In conclusion, inhibition of the AC/cAMP/PKA/HIF-1?/NLRP3 inflammasome pathway by M30 partially contributes to its attenuation of hepatocyte injury caused by ethanol exposure. PMID:25722794

Xiao, Jia; Lv, Yi; Lin, Bin; Tipoe, George L; Youdim, Moussa B H; Xing, Feiyue; Liu, Yingxia

2015-01-01

122

The molecular mechanism of fetal alcohol syndrome (FAS). I. Ethanol-induced growth suppression.  

PubMed

Of the birth defects associated with alcohol consumption during pregnancy, in situ growth retardation resulting in neonates that are small for gestational age is the most common observation in both humans and animal models. A variety of alcohol-induced alterations in maternal, placental and/or fetal physiology have been proposed as the basis for this retarded fetal growth. The molecular mechanism(s) of this retardation, however, is obscure; and it remains to be determined whether the growth suppression is the result of the action of ethanol or its metabolites on embryonic, maternal or placental tissue. Using the embryonic chick as a model which circumvents changes in maternal and placental function, we have measured ethanol-induced growth suppression as a function of embryonic age and ethanol dosage. The data suggest that ethanol per se suppresses the rate of cell division in embryonic tissue resulting in fewer cells/embryo for a given time of gestation. The suppression of cell division is proportional to the ethanol dose and appears to be related to ethanol-induced changes in the metabolism of the prostaglandin hormones and resulting changes in the cyclic-AMP levels of the developing embryos. PMID:6306496

Pennington, S N; Boyd, J W; Kalmus, G W; Wilson, R W

1983-01-01

123

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

124

A Novel Antioxidant Multitarget Iron Chelator M30 Protects Hepatocytes against Ethanol-Induced Injury  

PubMed Central

The multitarget iron chelator, M30, is a novel antioxidant and protective agent against oxidative stress in a spectrum of diseases. However, there is no report regarding its role in liver diseases. Since oxidative stress is one of the major pathological events during the progression of alcoholic liver diseases, the protective effects and mechanisms of M30 on ethanol-induced hepatocyte injury were investigated in this study. Rat hepatocyte line BRL-3A was pretreated with M30 prior to ethanol treatment. Cell death, apoptosis, oxidative stress, and inflammation were examined. Specific antagonists and agonists were applied to determine the involvements of hypoxia inducible factor-1 alpha (HIF-1?) and its upstream adenylate cyclase (AC)/cyclic AMP (cAMP)/protein kinase A (PKA)/HIF-1?/NOD-like receptor 3 (NLRP3) inflammasome pathway. We found that M30 significantly attenuated ethanol-induced cellular death, apoptosis, production of reactive oxygen species (ROS), and secretion of inflammatory cytokines and inhibited activation of the AC/cAMP/PKA/HIF-1?/NLRP3 inflammasome pathway. Inhibition and activation of the AC/cAMP/PKA/HIF-1? pathway mimicked and abolished the effects of M30, respectively. In conclusion, inhibition of the AC/cAMP/PKA/HIF-1?/NLRP3 inflammasome pathway by M30 partially contributes to its attenuation of hepatocyte injury caused by ethanol exposure. PMID:25722794

Lv, Yi; Lin, Bin; Tipoe, George L.; Youdim, Moussa B. H.; Xing, Feiyue; Liu, Yingxia

2015-01-01

125

Ethanol induces calcium influx via the Cch1-Mid1 transporter in Saccharomyces cerevisiae.  

PubMed

Yeast suffers from a variety of environmental stresses, such as osmotic pressure and ethanol produced during fermentation. Since calcium ions are protective for high concentrations of ethanol, we investigated whether Ca(2+) flux occurs in response to ethanol stress. We find that exposure of yeast to ethanol induces a rise in the cytoplasmic concentration of Ca(2+). The response is enhanced in cells shifted to high-osmotic media containing proline, galactose, sorbitol, or mannitol. Suspension of cells in proline and galactose-containing media increases the Ca(2+) levels in the cytoplasm independent of ethanol exposure. The enhanced ability for ethanol to induce Ca(2+) flux after the hypertonic shift is transient, decreasing rapidly over a period of seconds to minutes. There is partial recovery of the response after zymolyase treatment, suggesting that cell wall integrity affects the ethanol-induced Ca(2+) flux. Acetate inhibits the Ca(2+) accumulation elicited by the ethanol/osmotic stress. The Ca(2+) flux is primarily via the Cch1 Ca(2+) influx channel because strains carrying deletions of the cch1 and mid1 genes show greater than 90% reduction in Ca(2+) flux. Furthermore, a functional Cch1 channel reduced growth inhibition by ethanol. PMID:21259000

Courchesne, William E; Vlasek, Christopher; Klukovich, Rachel; Coffee, Sara

2011-05-01

126

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

PubMed

Excessive ethanol consumption during pregnancy causes fetal alcohol syndrome. We investigated the effect of [6]-gingerol on ethanol-induced embryotoxicity using a whole embryo culture system. The morphological changes of embryos and the gene expression patterns of the antioxidant enzymes cytosolic glutathione peroxidase (cGPx), cytoplasmic Cu/Zn superoxide dismutase (SOD1), and Mn-SOD (SOD2), and SOD activity were examined in the cultured mouse embryos exposed to ethanol (5 ?L/3 mL) and/or [6]-gingerol (1×10(-8) or 1×10(-7) ?g/mL) for 2 days. In ethanol-exposed embryos, the standard morphological score of embryos was significantly decreased compared with those of the control (vehicle) group. However, cotreatment of embryos with [6]-gingerol and ethanol significantly improved all of the developmental parameters except crownrump length and head length, compared with those of the ethanol alone group. The mRNA expression levels of cGPx and SOD2, not SOD1, were decreased consistently, SOD activity were significantly decreased compared with the control group. However, the decreases in mRNA levels of antioxidant enzymes and SOD activity were significantly restored to the control levels by [6]-gingerol supplement. These results indicate that [6]-gingerol has a protective effect against ethanol-induced teratogenicity during mouse embryogenesis. PMID:22297756

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

2012-01-01

127

Agrimonia eupatoria protects against chronic ethanol-induced liver injury in rats.  

PubMed

This study examined the hepatoprotective effects of Agrimonia eupatoria water extract (AE) against chronic ethanol-induced liver injury. Rats were fed a Lieber-DeCarli liquid diet for 8 weeks. Animals were treated orally with AE at 10, 30, 100, and 300 mg/kg/day. After chronic consumption of ethanol, serum aminotransferase activities and pro-inflammatory cytokines markedly increased, and those increases were attenuated by AE. The cytochrome P450 2E1 activity and lipid peroxidation increased after chronic ethanol consumption, while reduced glutathione concentration decreased. Those changes were attenuated by AE. Chronic ethanol consumption increased the levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expression, inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression, and nuclear translocation of nuclear factor-kappa B, which was attenuated by AE. Our results suggest that AE ameliorates chronic ethanol-induced liver injury, and that protection is likely due to the suppression of oxidative stress and TLR-mediated inflammatory signaling. PMID:22525864

Yoon, Seong-Jin; Koh, Eun-Ji; Kim, Chang-Soo; Zee, Ok-Pyo; Kwak, Jong-Hwan; Jeong, Won-Jin; Kim, Jee-Hyun; Lee, Sun-Mee

2012-07-01

128

Neuroprotective profile of pyruvate against ethanol-induced neurodegeneration in developing mice brain.  

PubMed

Exposure to ethanol during developmental stages leads to several types of neurological disorders. Apoptotic neurodegeneration due to ethanol exposure is a main feature in alcoholism. Exposure of developing animals to alcohol induces apoptotic neuronal death and causes fetal alcohol syndrome. In the present study, we observed the possible protective effect of pyruvate against ethanol-induced neurodegeneration. Exposure of developing mice to ethanol (2.5 g/kg) induces apoptotic neurodegeneration and widespread neuronal cell death in the cortex and thalamus. Co-treatment of pyruvate (500 mg/kg) protects neuronal cell against ethanol by the reduced expression of caspase-3 in these brain regions. Immunohistochemical analysis and TUNNEL at 24 h showed that apoptotic cell death induced by ethanol in the cortex and thalamus is reduced by pyruvate. Histomorphological analysis at 24 h with cresyl violet staining also proved that pyruvate reduced the number of neuronal cell loss in the cortex and thalamus. The results showed that ethanol increased the expression of caspase-3 and thus induced apoptotic neurodegeneration in the developing mice cortex and thalamus, while co-treatment of pyruvate inhibits the induction of caspase-3 and reduced the cell death in these brain regions. These findings, therefore, showed that treatment of pyruvate inhibits ethanol-induced neuronal cell loss in the postnatal seven (P7) developing mice brain and may appear as a safe neuroprotectant for treating neurodegenerative disorders in newborns and infants. PMID:23494720

Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Kim, Tae Hyun; Lee, Hae Young; Kim, Myeong Ok

2013-12-01

129

Electrolyzed-reduced water inhibits acute ethanol-induced hangovers in Sprague-Dawley rats.  

PubMed

Ethanol consumption disturbs the balance between the pro- and anti-oxidant systems of the organism, leading to oxidative stress. Electrolyzed-reduced water (ERW) is widely used by people in East Asia for drinking purposes because of its therapeutic properties including scavenging effect of reactive oxygen species. This study was performed to investigate the effect of ERW on acute ethanol-induced hangovers in Sprague-Dawley rats. Alcohol concentration in serum of ERW-treated rats showed significant difference at 1 h, 3 h and 5 h respectively as compared with the rats treated with distilled water. Both alcohol dehydrogenase type 1 and acetaldehyde dehydrogenase related with oxidation of alcohol were significantly increased in liver tissue while the level of aspartate aminotransferase and alanine aminotransferase in serum was markedly decreased 24 h after pre-oral administration of ERW. Moreover, oral administration of ERW significantly activated non-ezymatic (glutathione) and enzymatic (glutathione peroxidase, glutathione-S-transferase, Cu/Zn-superoxide dismutase and catalase) antioxidants in liver tissues compared with the control group. These results suggest that drinking ERW has an effect of alcohol detoxification by antioxidant mechanism and has potentiality for relief of ethanol-induced hangover symptoms. PMID:19887722

Park, Seung-Kyu; Qi, Xu-Feng; Song, Soon-Bong; Kim, Dong-Heui; Teng, Yung-Chien; Yoon, Yang-Suk; Kim, Kwang-Yong; Li, Jian-Hong; Jin, Dan; Lee, Kyu-Jae

2009-10-01

130

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). PMID:23724090

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

131

Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement.  

PubMed

The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus. PMID:25378912

Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

2014-01-01

132

Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement  

PubMed Central

The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus. PMID:25378912

Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

2014-01-01

133

Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction.  

PubMed

Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globular adiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption. PMID:22842631

Nepal, Saroj; Kim, Mi Jin; Subedi, Amit; Lee, Eung-Seok; Yong, Chul Soon; Kim, Jung-Ae; Kang, WonKu; Kwak, Mi-Kyung; Arya, Dharamvir Singh; Park, Pil-Hoon

2012-10-01

134

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. PMID:24250716

Y?ld?z, Oktay; Can, Zehra; Saral, Özlem; Yulu?, Esin; Öztürk, Ferhat; Aliyaz?c?o?lu, Rezzan; Canpolat, Sinan; Kolayl?, Sevgi

2013-01-01

135

PPAR? agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair  

PubMed Central

Background/Aims Chronic ethanol exposure impairs liver regeneration due to inhibition of insulin signaling and oxidative injury. PPAR agonists function as insulin sensitizers and anti-inflammatory agents. We investigated whether treatment with a PPAR? agonist could restore hepatic insulin sensitivity, survival signaling, and regenerative responses vis-a-vis chronic ethanol feeding. Methods Adult rats were fed isocaloric liquid diets containing 0% or 37% ethanol, and administered a PPAR? agonist by i.p. injection. We used liver tissue to examine histopathology, gene expression, oxidative stress, insulin signaling, and regenerative responses to 2/3 hepatectomy. Results Chronic ethanol feeding caused insulin resistance, increased oxidative stress, lipid peroxidation, DNA damage, and hepatocellular injury in liver. These effects were associated with reduced insulin receptor binding and affinity, impaired survival signaling through PI3K/Akt/GSK3?, and reduced expression of insulin responsive genes mediating energy metabolism and tissue remodeling. PPAR? agonist treatment reduced ethanol-mediated hepatic injury, oxidative stress, lipid peroxidation, and insulin resistance, increased signaling through PI3K/Akt/GSK3?, and enhanced the regenerative response to partial hepatectomy. Conclusions PPAR? agonist administration may attenuate the severity of chronic ethanol-induced liver injury and ethanol’s adverse effects on the hepatic repair by restoring insulin responsiveness, even in the context of continued high-level ethanol consumption. PMID:19398227

Pang, Maoyin; de la Monte, Suzanne M.; Longato, Lisa; Tong, Ming; He, Jiman; Chaudhry, Rajeeve; Duan, Kevin; Ouh, Jiyun; Wands, Jack R.

2009-01-01

136

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

PubMed

Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (?3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial ?-oxidation of fatty acids (Cpt1? and Ppar-? expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage. PMID:25101998

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

2014-01-01

137

Combination of Alcohol and Fructose Exacerbates Metabolic Imbalance in Terms of Hepatic Damage, Dyslipidemia, and Insulin Resistance in Rats  

PubMed Central

Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (?3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial ?-oxidation of fatty acids (Cpt1? and Ppar-? expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage. PMID:25101998

Schultze, Frank Christian; Wilting, Jörg; Mihm, Sabine; Raddatz, Dirk; Ramadori, Giuliano

2014-01-01

138

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

PubMed Central

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

2014-01-01

139

Xanthohumol, a main prenylated chalcone from hops, reduces liver damage and modulates oxidative reaction and apoptosis in hepatitis C virus infected Tupaia belangeri.  

PubMed

Hepatitis C virus (HCV) infection in Tupaia belangeri (Tupaia) represents an important model of HCV infection. Xanthohumol (XN), a major prenylated chalcone from hops, has various biological activities including hepatopreventive and anti-viral activities. In this study, Tupaias infected with HCV RNA positive serum were used to evaluate the effects of XN on liver damage, oxidative reaction, apoptosis and viral protein expression in liver tissues. The Tupaias inoculated with HCV positive serum had elevated serum aminotransferase levels and inflammation, especially hepatic steatosis, and HCV core protein expression in liver tissue. In the animals inoculated with HCV positive serum, XN significantly decreased aminotransferase levels, histological activity index, hepatic steatosis score and transforming growth factor ?1 expression in liver tissue compared with the animals without XN intervention. XN reduced HCV core protein expression in liver tissue compared with those without XN intervention but the difference was not significant. XN significantly decreased malondialdehyde, potentiated superoxide dismutase and glutathione peroxidase, reduced Bax expression, promoted Bcl-xL and inhibited caspase 3 activity in liver tissues compared with the animals without XN intervention. These results indicate that XN may effectively improve hepatic inflammation, steatosis and fibrosis induced by HCV in Tupaias primarily through inhibition of oxidative reaction and regulation of apoptosis and possible suppression of hepatic stellate cell activation. The anti-HCV potential of XN needs further investigation. PMID:23669332

Yang, Mingbo; Li, Na; Li, Fang; Zhu, Qianqian; Liu, Xi; Han, Qunying; Wang, Yawen; Chen, Yanping; Zeng, Xiaoyan; Lv, Yi; Zhang, Pingping; Yang, Cuiling; Liu, Zhengwen

2013-08-01

140

Ethanol-induced tolerance and sex-dependent sensitization in preweanling rats.  

PubMed

According to genetic studies, the acute stimulating effect of ethanol seems to be associated with an increased predisposition to consume large quantities of ethanol. Ethanol-induced stimulation has been rarely reported in adult rats. However, infant rats, particularly during the second postnatal week of life, are highly sensitive to ethanol-induced behavioral activation. They also consume more ethanol than in later ontogenetic stages. In adult mice repeated ethanol experience usually results in sensitization to the stimulating effect of ethanol, while tolerance is the predominant result in rats. The present study was designed to explore in rats whether repeated exposure to ethanol during infancy modifies subjects' sensitivity to the stimulating effect of the drug, either increasing or decreasing its magnitude (i.e. sensitization or tolerance, respectively). Furthermore, we also explored the possible context-modulation of these effects. In two experiments, subjects were trained with water or ethanol (2.5 g/kg) between postnatal days (PDs) 8 and 12 (Experiment 1) or between PDs 14 and 18 (Experiment 2), and tested in response to water or ethanol two days later. In these experiments we identified three variables that critically modulate the effect of the repeated ethanol exposure: sex, context and age. Ethanol exclusively and consistently induced locomotor sensitization in males trained outside of the testing context (Experiments 1a and 1b), while tolerance to the stimulating effect of ethanol was observed in males and females trained in the testing context (Experiment 1a). In Experiment 2 tolerance was detected in females trained outside of the testing context. Finally, experience with the testing context during training strongly attenuated the stimulating effect of ethanol in the older subjects (Experiment 2). These results show that the same ethanol treatment can produce opposite effects (tolerance or sensitization) and demonstrate the involvement of Pavlovian conditioning in the development of tolerance. Furthermore, sex was revealed as an important factor to take into consideration in the analysis of chronic experience with ethanol during infancy. We can conclude that specific ontogenetic stages can be used to study the biological determinants underlying both ethanol-induced tolerance and sensitization, and the environmental modulators of these effects. PMID:25446214

Castello, S; Revillo, D A; Molina, J C; Arias, C

2015-02-01

141

14-Deoxyandrographolide alleviates ethanol-induced hepatosteatosis through stimulation of AMP-activated protein kinase activity in rats.  

PubMed

Andrographis paniculata (AP) is a traditional medicinal plant of Ayurveda. It grows widely in Asia and is prescribed in the treatment of liver diseases. Here we have investigated the beneficial role of 14-deoxyandrographolide (14-DAG), a bioactive diterpenoid from AP, against alcoholic steatosis in rats. 14-DAG was extracted from aerial parts (leaves and stems) of AP. Rats were fed with ethanol for 8 weeks. Animals were treated with 14-DAG during the last 4 weeks of ethanol treatment. In vitro studies were undertaken in a human hepatocellular liver carcinoma cell line culture. Hepatosteatosis was assessed from histopathological studies of liver sections. Acetyl-CoA, malonyl-CoA, and triglyceride contents were determined using commercially available kits. Fatty acid synthesis was evaluated from incorporation of 1-(14)C acetate. Regulation of fatty acid oxidation and lipogenesis were monitored with immunoblotting and immunoprecipitation studies. Ethanol exposure led to hepatotoxicity, as evident from the marked enhancement in the levels of AST and ALT. The values decreased almost to control levels in response to 14-DAG treatment. Results showed that ethanol feeding induced deactivation of AMP-activated protein kinase (AMPK) that led to enhanced lipid synthesis and decreased fatty acid oxidation, culminating in hepatic fat accumulation. Treatment with 14-DAG activated AMPK through induction of cyclic AMP-protein kinase A pathway. Activation of AMPK was followed by down-regulation of sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase, leading to suppression of lipogenesis. This was associated with up-regulation of sirtuin 1 and depletion of malonyl-CoA, in favor of increased fatty acid oxidation. 14-DAG controlled ethanol-induced hepatosteatosis by interfering with dysregulation of lipid metabolism. In conclusion, our results indicated that 14-DAG was capable of preventing the development of fatty liver through AMPK-mediated regulation of lipid metabolism. This finding supported the hepatoprotective role of 14-DAG, which might serve as a therapeutic option to alleviate hepatosteatosis in chronic alcoholism. PMID:24507479

Mandal, Samir; Mukhopadhyay, Sibabrata; Bandhopadhyay, Sukdeb; Sen, Gargi; Biswas, Tuli

2014-03-01

142

Association between Noninvasive Fibrosis Markers and Cardio-Vascular Organ Damage among Adults with Hepatic Steatosis  

PubMed Central

Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm, (OR 3.95, 95% CI 1.12–13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22–10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors. PMID:25111713

Sesti, Giorgio; Sciacqua, Angela; Fiorentino, Teresa Vanessa; Perticone, Maria; Succurro, Elena; Perticone, Francesco

2014-01-01

143

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...

144

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....

145

Protective Effect of Tragopogon Graminifolius DC Against Ethanol Induced Gastric Ulcer  

PubMed Central

Background Gastric ulcer is a serious digestive system problem and affects 5% to 10% of people during their life. Chemical antigastric ulcer drugs have side effect, cannot prevent recurrence of ulcer and also show drug interaction with many other medicaments. Tragopogon graminifolius DC.(TG) is a herb which is widely used in the west of Iran and traditionally consumed for the treatment of gastrointestinal disorders. TG was introduced as one of the most beneficial plants for digestive ulcer in Iranian traditional medicine. Objectives The aim of the present study was to determine the acute toxicity and protective effect of hydroalcoholic extract of TG (HeTG) against ethanol induced gastric ulcer. Materials and Methods Male Wistar rats were divided into five groups (n = 7). HeTG at the doses of 50, 100, and 150 mg/kg were administered orally for 15 days and gastric ulcer was induced by pure ethanol (1 ml/200gr body weight). Ulcer index and protective rate were calculated and histological changes were determined. Results HeTG was nontoxic up to 2000 mg/Kg. Ulcer index decreased in extract groups significantly. Protective rates of HeTG were 48.94%, 46.39%, and 43.99% in 50, 100, and 150 mg/kg extract, respectively. 50 mg/kg HeTG group had higher protective effect. There was relatively normal cellular arrangement in HeTG groups. Conclusions TG showed protective effect against ethanol induced gastric ulcer. This study confirmed traditional medicine claims of TG. PMID:24616792

Farzaei, Mohamad Hosein; Khazaei, Mozafar; Abbasabadei, Zahra; Feyzmahdavi, Maryam; Mohseni, Gholam Reza

2013-01-01

146

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

147

Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma.  

PubMed

In Egypt, hepatocellular carcinoma (HCC) was predicted to continue to rise over the next few decades causing a national problem. Meanwhile, glypican-3 (GPC3), a highly expressed glypican, has emerged as a potential target for HCC immunotherapy. Therefore, we aimed to identify the impact of blocking GPC3 on liver damage in HCC as well as a possible mechanism. Fifty four HCC patients, 20 cirrhotic patients and 10 healthy subjects were recruited. Serum levels of GPC3, sulfatase-2 (SULF-2), heparan sulfate proteoglycan (HSPG), insulin-like growth factor-II (IGF-II) were measured by ELISA. In parallel, HCC was induced in 40 male Sprague-Dawley rats in presence/absence of antiGPC-3. Liver impairment was detected by investigating liver sections stained with hematoxylin/eosin and serum ?-fetoprotein (AFP). Liver homogenates of GPC3, SULF-2, and HSPG were measured by ELISA. Gene expression of caspase-3 and IGF-II were assayed by RT-PCR. HCC patients showed significant elevated serum levels of GPC3, IGF-II and SULF-2 accompanied by decreased HSPG. However, treatment of HCC rats with antiGPC-3 significantly reduced serum AFP and showed nearly normal hepatocytes. In addition, antiGPC-3 significantly reduced elevated liver homogenates protein levels of GPC3 and SULF-2 and gene expression of IGF-II and caspase-3. antiGPC-3 restored the reduced hepatic HSPG. antiGPC-3 showed anti-tumor activity as well as hepatoprotective effects. antiGPC-3-chemoprotective effect can be explained by forced reduction of IGF-II expression, restoration of HSPGs, deactivation of SULF-2 and reduction of gene expression of caspase-3. Targeting GPC3 is a promising therapeutic approach for HCC. PMID:25449037

Zaghloul, Randa A; El-Shishtawy, Mamdouh M; El Galil, Khaled H Abd; Ebrahim, Mohamed A; Metwaly, AbdelHamid A; Al-Gayyar, Mohammed M

2015-01-01

148

Effect of Allyl Alcohol-induced Sublethal Hepatic Damage upon Doxorubicin Metabolism and Toxicity in the Rabbit1  

Microsoft Academic Search

A model of hepatic dysfunction in vivo has been developed in rabbits to determine the effects of sublethal hepatocellular necrosis upon doxo- rubicin pharmacology. Eight New Zealand white rabbits were given 3 mg\\/kg doxorubicin i.v. Plasma doxorubicin and metabolite pharmacoki- netics were determined and toxicity assessed by nadir complete blood counts. Hepatic function was assessed by the pulmonary excretion rate

Dean E. Brenner; Lowell B. Anthony; Susan Halter; N. Lindsay Harris; Jerry C. Collins; Kenneth R. HÃ

149

Relation between ethanol induced changes in plasma catecholines during stress and voluntary ethanol preference  

SciTech Connect

N/NIH rats (N = 10) were implanted with venous catheters to permit stressless chronic, repeated blood withdrawal. Following surgical recovery, the rats were restrained to a lab counter top for 30 min after injection with saline or low dose (0.5 g/kg) ethanol. Blood was repeatedly withdrawn to determine AUC production of NE and E to assess the effect that low dose ethanol has on stress responsiveness. Between saline injection restraint and ethanol injection restraint conditions no differences in NE or E AUC were apparent. A 2- bottle preference test for ethanol was then performed over 21 days. Multiple regression analyses of NE saline restraint and ethanol restraint could predict ethanol consumption to the p = .02 level with R/sup 2/ = .681. Multiple regressions of E saline restraint and E ethanol restraint could predict ethanol consumption to the p = .01 level with R/sup 2/ = .746. These data suggest that ethanol induced increases in plasma NE and E during stress can predict later voluntary ethanol consumption between the ranges of .13 and 1.05 g ethanol/kg/day. This data seems to be more in line with an arousal or withdrawal relationship between ethanol consumption and stress than by a simple tension reduction formulation based on plasma NE or E.

Pashko, S.

1986-03-01

150

Ethanol-induced epigenetic regulations at the Bdnf gene in C57BL/6J mice.  

PubMed

High ethanol intake is well known to induce both anxiolytic and anxiogenic effects, in correlation with chromatin remodeling in the amygdaloid brain region and deficits in cell proliferation and survival in the hippocampus of rodents. Whether only moderate but chronic ethanol intake in C57BL/6J mice could also have an impact on chromatin remodeling and neuroplasticity was addressed here. Chronic ethanol consumption in a free choice paradigm was found to induce marked changes in the expression of genes implicated in neural development and histone post-translational modifications in the mouse hippocampus. Transcripts encoding neural bHLH activators and those from Bdnf exons II, III and VI were upregulated, whereas those from Bdnf exon VIII and Hdacs were downregulated by ethanol compared with water consumption. These ethanol-induced changes were associated with enrichment in both acetylated H3 at Bdnf promoter PVI and trimethylated H3 at PII and PIII. Conversely, acetylated H3 at PIII and PVIII and trimethylated H3 at PVIII were decreased in ethanol-exposed mice. In parallel, hippocampal brain-derived neurotrophic factor (BDNF) levels and TrkB-mediated neurogenesis in the dentate gyrus were significantly enhanced by ethanol consumption. These results suggest that, in C57BL/6J mice, chronic and moderate ethanol intake produces marked epigenetic changes underlying BDNF overexpression and downstream hippocampal neurogenesis. PMID:24776738

Stragier, E; Massart, R; Salery, M; Hamon, M; Geny, D; Martin, V; Boulle, F; Lanfumey, L

2015-03-01

151

Ethanol-Induced Activation of ATP-Dependent Proton Extrusion in Elodea densa Leaves 1  

PubMed Central

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

Marrè, Maria T.; Venegoni, Alberto; Moroni, Anna

1992-01-01

152

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

Marrè, M T; Venegoni, A; Moroni, A

1992-11-01

153

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

154

The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage – A light and electron microscopic study  

Microsoft Academic Search

Summary.  ?The results regarding taurine pretreatment on CCl4-induced hepatic injury are controversial. To assess the therapeutic efficacy of taurine on rat liver injury, hepatic malondialdehyde,\\u000a glutathione, and hydroxyproline levels together with morphologic alterations in the liver following CCl4 administration were investigated. The rats were divided into three groups. Taurine-treated animals received 15?ml\\/kg\\/day\\u000a of a 5% taurine solution by a gastric tube

S. Dinçer; S. Özenirler; E. Öz; G. Akyol; C. Özo?ul

2002-01-01

155

Hepatitis A  

MedlinePLUS

... have to be hospitalized? Will I have permanent liver damage? Source Hepatitis A by SC Brundage M.D., M.P.H. and AN Fitzpatrick, M.P.H. (American Family Physician June 15, 2006, http://www.aafp.org/afp/20060615/2162.html) Written by familydoctor.org editorial ...

156

Central adenosinergic system involvement in ethanol-induced motor incoordination in mice  

SciTech Connect

To clarify if the behavioral interaction between ethanol and adenosine reported previously occur centrally or due to a peripheral hemodynamic change, the effect of i.c.v. adenosine agonists, N6-(R-phenylisopropyl)adenosine (R-PIA), N6-(S-phenylisopropyl)adenosine, 5'-(N-cyclopropyl)-carboxamidoadenosine, antagonists, theophylline and 8-p-(sulfophenyl)theophylline as well as enprofylline on ethanol-(i.p.)-induced motor incoordination was evaluated by rotorod. Adenosine agonists and antagonists dose dependently accentuated and attenuated, respectively, ethanol-induced motor incoordination, thereby suggesting a central mechanism of adenosine modulation of this effect of ethanol and confirmed our previous reports in which adenosine agonists and antagonists were given i.p. Enprofylline, a weak adenosine antagonist but potent inhibitor of cyclic AMP phosphodiesterase, did not alter ethanol's motor incoordination, further supporting involvement of brain adenosine receptor mechanism(s) in ethanol-adenosine interactions. Results from R-PIA and N6-(S-phenylisopropyl)adenosine experiments showed nearly a 40-fold greater potency of R-vs. S-diastereoisomer, suggesting predominance of adenosine A1 subtype. However, 5'-(N-cyclopropyl)-carboxamidoadenosine data indicate complexity of the mechanism(s) and point toward an additional involvement of a yet unknown subtype of adenosine A2. No effect of ethanol on blood or brain levels of (3H)R-PIA was noted and sufficient amount of the latter entered the brain to suggest adenosine receptor activation adequate to produce behavioral interaction with ethanol. There was no escape of i.c.v.-administered (3H)R-PIA from brain to the peripheral circulation ruling out a peripheral and supporting a central mechanism of ethanol-adenosine interaction.

Dar, M.S. (East Carolina Univ., Greenville, NC (USA))

1990-12-01

157

Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats  

PubMed Central

Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP) on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP) and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (??) and ST36 (???) were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX), B-cell lymphoma 2 (Bcl-2) and Transforming growth factor-beta 1 (TGF-?1). Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

Park, Jae-Heung; Jang, Kyung-Jun; Kim, Cheol-Hong; Kim, Jung-Hee; Kim, Young-Kyun; Yoon, Hyun-Min

2015-01-01

158

Molecular Mechanisms of Ethanol-Induced Pathogenesis Revealed by RNA-Sequencing  

PubMed Central

Acinetobacter baumannii is a common pathogen whose recent resistance to drugs has emerged as a major health problem. Ethanol has been found to increase the virulence of A. baumannii in Dictyostelium discoideum and Caenorhabditis elegans models of infection. To better understand the causes of this effect, we examined the transcriptional profile of A. baumannii grown in the presence or absence of ethanol using RNA-Seq. Using the Illumina/Solexa platform, a total of 43,453,960 reads (35 nt) were obtained, of which 3,596,474 mapped uniquely to the genome. Our analysis revealed that ethanol induces the expression of 49 genes that belong to different functional categories. A strong induction was observed for genes encoding metabolic enzymes, indicating that ethanol is efficiently assimilated. In addition, we detected the induction of genes encoding stress proteins, including upsA, hsp90, groEL and lon as well as permeases, efflux pumps and a secreted phospholipase C. In stationary phase, ethanol strongly induced several genes involved with iron assimilation and a high-affinity phosphate transport system, indicating that A. baumannii makes a better use of the iron and phosphate resources in the medium when ethanol is used as a carbon source. To evaluate the role of phospholipase C (Plc1) in virulence, we generated and analyzed a deletion mutant for plc1. This strain exhibits a modest, but reproducible, reduction in the cytotoxic effect caused by A. baumannii on epithelial cells, suggesting that phospholipase C is important for virulence. Overall, our results indicate the power of applying RNA-Seq to identify key modulators of bacterial pathogenesis. We suggest that the effect of ethanol on the virulence of A. baumannii is multifactorial and includes a general stress response and other specific components such as phospholipase C. PMID:20368969

Camarena, Laura; Bruno, Vincent; Euskirchen, Ghia; Poggio, Sebastian; Snyder, Michael

2010-01-01

159

22-S-Hydroxycholesterol protects against ethanol-induced liver injury by blocking the auto/paracrine activation of MCP-1 mediated by LXR?.  

PubMed

Chronic ethanol consumption causes hepatic steatosis and inflammation, which are associated with liver hypoxia. Monocyte chemoattractant protein-1 (MCP-1) is a hypoxia response factor that determines recruitment and activation of monocytes to the site of tissue injury. The level of MCP-1 is elevated in the serum and liver of patients with alcoholic liver disease (ALD); however, the molecular details regarding the regulation of MCP-1 expression are not yet understood completely. Here, we show the role of liver X receptor ? (LXR?) in the regulation of MCP-1 expression during the development of ethanol-induced fatty liver injury, using an antagonist, 22-S-hydroxycholesterol (22-S-HC). First, administration of 22-S-HC attenuated the signs of liver injury with decreased levels of MCP-1 and its receptor CCR2 in ethanol-fed mice. Second, hypoxic conditions or treatment with the LXR? agonist GW3965 significantly induced the expression of MCP-1, which was completely blocked by treatment with 22-S-HC or infection by shLXR? lentivirus in the primary hepatocytes. Third, over-expression of LXR? or GW3965 treatment increased MCP-1 promoter activity by increasing the binding of hypoxia-inducible factor-1? to the hypoxia response elements, together with LXR?. Finally, treatment with recombinant MCP-1 increased the level of expression of LXR? and LXR?-dependent lipid droplet accumulation in both hepatocytes and Kupffer cells. These data show that LXR? and its ligand-induced up-regulation of MCP-1 and MCP-1-induced LXR?-dependent lipogenesis play a key role in the autocrine and paracrine activation of MCP-1 in the pathogenesis of alcoholic fatty liver disease, and that this activation may provide a promising new target for ALD therapy.Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:25557254

Na, Tae-Young; Han, Young-Hyun; Ka, Na-Lee; Park, Han-Su; Kang, Yun Pyo; Kwon, Sung Won; Lee, Byung-Hoon; Lee, Mi-Ock

2015-04-01

160

Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver  

PubMed Central

Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-? activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-? overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-? expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-? overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-? inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease. PMID:25356030

Liu, Jinyao

2014-01-01

161

Nanoscale hepatoprotective herbal decoction attenuates hepatic stellate cell activity and chloroform-induced liver damage in mice  

PubMed Central

Background San-Huang-Xie-Xin-Tang (SHXXT) decoction, a traditional Chinese medicine containing Rhei rhizome, Coptidis rhizome, and Scutellariae radix, is widely used in hepatoprotective therapy. However, preparation of the decoction requires addition of boiling water that causes loss of numerous effective components. Methods To improve the bioavailability of the decoction, nanoscale SHXXT was developed. Chloroform-induced liver injury and hepatic stellate cell activity in mice were used to demonstrate the hepatoprotective characteristics of nanoscale SHXXT decoction. Results Liver/body weight ratio and serum aspartate and alanine aminotranferase levels were recovered by the nanoscale SHXXT. TIMP-1 gene expression was inhibited and MMP-2 gene expression was accelerated in activated hepatic stellate cells. Conclusion Nanoscale SHXXT decoction prepared in room temperature water could have preserved hepatoprotective ability. The results of this study indicate that nanoscale SHXXT could be extracted easily. The simple preparation of this herbal decoction is more convenient and energy-efficient. PMID:21760731

Huang, Sherry; Chang, Shu-Jen; Yang, Miffy; Chen, Justin Jin-Ching; Chang, Walter H

2011-01-01

162

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

163

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

164

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. PMID:24841742

Cunningham, Christopher L

2014-08-01

165

Know More Hepatitis  

MedlinePLUS

... cause serious health problems including liver damage, cirrhosis, liver cancer and even death. In fact, Hepatitis C is a leading cause of liver cancer and the #1 cause of liver transplants. Many ...

166

Hepatitis C  

MedlinePLUS

Hepatitis C is a viral disease that leads to swelling (inflammation) of the liver. Other types of viral hepatitis ... Hepatitis C infection is caused by the hepatitis C virus (HCV). You can catch hepatitis C if the blood ...

167

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

168

A crucial role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling  

Technology Transfer Automated Retrieval System (TEKTRAN)

Female skeletal responses to ethanol may vary depending on the physiologic status (viz. cycling, pregnancy, lactation). Nonetheless, ethanol-induced oxidative stress appears to be the key event leading to skeletal toxicity. In the current study, we chronically infused EtOH-containing liquid diets ...

169

A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling  

Technology Transfer Automated Retrieval System (TEKTRAN)

The mechanisms by which chronic ethanol intake induces bone loss remain unclear. In females, the skeletal response to ethanol varies depending on physiologic status (viz. cycling, pregnancy, lactation). Ethanol-induced oxidative stress appears to be a key event leading to skeletal toxicity. In the c...

170

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...

171

A crucial role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through Inhibition of Wnt / Beta-catenin Signaling  

Technology Transfer Automated Retrieval System (TEKTRAN)

The mechanisms by which chronic ethanol intake induces bone loss remain largely unclear. Especially in females, skeletal response to ethanol may vary depending on the physiologic status (viz. cycling, pregnancy, lactation). Nonetheless, ethanol-induced oxidative stress appears to be the key event le...

172

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

173

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. PMID:24944640

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

2014-01-01

174

Oxytocin prevents ethanol actions at ? subunit-containing GABAA receptors and attenuates ethanol-induced motor impairment in rats.  

PubMed

Even moderate doses of alcohol cause considerable impairment of motor coordination, an effect that substantially involves potentiation of GABAergic activity at ? subunit-containing GABAA receptors (?-GABAARs). Here, we demonstrate that oxytocin selectively attenuates ethanol-induced motor impairment and ethanol-induced increases in GABAergic activity at ?-GABAARs and that this effect does not involve the oxytocin receptor. Specifically, oxytocin (1 µg i.c.v.) given before ethanol (1.5 g/kg i.p.) attenuated the sedation and ataxia induced by ethanol in the open-field locomotor test, wire-hanging test, and righting-reflex test in male rats. Using two-electrode voltage-clamp electrophysiology in Xenopus oocytes, oxytocin was found to completely block ethanol-enhanced activity at ?4?1? and ?4?3? recombinant GABAARs. Conversely, ethanol had no effect when applied to ?4?1 or ?4?3 cells, demonstrating the critical presence of the ? subunit in this effect. Oxytocin had no effect on the motor impairment or in vitro effects induced by the ?-selective GABAAR agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, which binds at a different site on ?-GABAARs than ethanol. Vasopressin, which is a nonapeptide with substantial structural similarity to oxytocin, did not alter ethanol effects at ?-GABAARs. This pattern of results confirms the specificity of the interaction between oxytocin and ethanol at ?-GABAARs. Finally, our in vitro constructs did not express any oxytocin receptors, meaning that the observed interactions occur directly at ?-GABAARs. The profound and direct interaction observed between oxytocin and ethanol at the behavioral and cellular level may have relevance for the development of novel therapeutics for alcohol intoxication and dependence. PMID:25713389

Bowen, Michael T; Peters, Sebastian T; Absalom, Nathan; Chebib, Mary; Neumann, Inga D; McGregor, Iain S

2015-03-10

175

Pyranocycloartobiloxanthone A, a novel gastroprotective compound from Artocarpus obtusus Jarret, against ethanol-induced acute gastric ulcer in vivo.  

PubMed

Pyranocycloartobiloxanthone A (PA), a xanthone derived from the Artocarpus obtusus Jarret, belongs to the Moraceae family which is native to the tropical forest of Malaysia. In this study, the efficacy of PA as a gastroprotective compound was examined against ethanol-induced ulcer model in rats. The rats were pretreated with PA and subsequently exposed to acute gastric lesions induced by absolute ethanol. The ulcer index, gastric juice acidity, mucus content, histological analysis, glutathione (GSH) levels, malondialdehyde level (MDA), nitric oxide (NO) and non-protein sulfhydryl group (NP-SH) contents were evaluated in vivo. The activities of PA as anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitor and free radical scavenger were also investigated in vitro. The results showed that the oral administration of PA protects gastric mucosa from ethanol-induced gastric lesions. PA pretreatment significantly (p<0.05) restored the depleted GSH, NP-SH and NO levels in the gastric homogenate. Moreover, PA significantly (p<0.05) reduced the elevated MDA level due to ethanol administration. The gastroprotective effect of PA was associated with an over expression of HSP70 and suppression of Bax proteins in the ulcerated tissue. In addition, PA exhibited a potent FRAP value and significant COX-2 inhibition. It also showed a significant minimum inhibitory concentration (MIC) against H. pylori bacterium. The efficacy of PA was accomplished safely without the presence of any toxicological parameters. The results of the present study indicate that the gastroprotective effect of PA might contribute to the antioxidant and anti-inflammatory properties as well as the anti-apoptotic mechanism and antibacterial action against Helicobacter pylori. PMID:23570997

Sidahmed, Heyam M A; Hashim, Najihah Mohd; Amir, Junaidah; Abdulla, Mahmood Ameen; Hadi, A Hamid A; Abdelwahab, Siddig Ibrahim; Taha, Manal Mohamed Elhassan; Hassandarvish, Pouya; Teh, Xinsheng; Loke, Mun Fai; Vadivelu, Jamuna; Rahmani, Mawardi; Mohan, Syam

2013-07-15

176

Alterations in Ethanol-Induced Behaviors and Consumption in Knock-In Mice Expressing Ethanol-Resistant NMDA Receptors  

PubMed Central

Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ?0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75–2.0 g/kg; IP) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol. PMID:24244696

den Hartog, Carolina R.; Beckley, Jacob T.; Smothers, Thetford C.; Lench, Daniel H.; Holseberg, Zack L.; Fedarovich, Hleb; Gilstrap, Meghin J.; Homanics, Gregg E.; Woodward, John J.

2013-01-01

177

Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats.  

PubMed

The hepatoprotective activities of Lycium chinense Miller (LC) fruit extract and its component betaine were investigated under carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. The treatment of LC fruit extract significantly suppressed the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera of CCl4 injured rats, and restored the decreased levels of anti-oxidant enzymes such as total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and suppressed the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and -2. To visualize the potential activity of betaine, a component of LC fruit, betaine was substituted for LC extract in CCl4 injured rats. The biochemical profile in CCl4 injured rats co-treated with betaine matched those of LC fruit treated CCl4 injured rats. The ameliorative effects of LC extract, as well as betaine, were also confirmed by histopathological examination. Collectively, the present findings imply that LC fruit, via its component betaine, mitigate CCl4-induced hepatic injury by increasing antioxidative activity and decreasing inflammatory mediators including iNOS and COX-1/COX-2. PMID:24998029

Ahn, Meejung; Park, Jong Sang; Chae, Sungwook; Kim, Seungjoon; Moon, Changjong; Hyun, Jin Won; Shin, Taekyun

2014-07-01

178

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

179

Hepatitis C  

MedlinePLUS

... may include: Fatigue Nausea Vomiting Loss of appetite Jaundice (yellowing of the skin and the whites of ... vaccine for hepatitis C. (There are vaccines for hepatitis A and hepatitis B.) If you have hepatitis C, ...

180

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.  

PubMed

Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent. PMID:24113767

Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei; Zhou, Zhanxiang

2013-12-01

181

Nicotine improves ethanol-induced impairment of memory: possible involvement of nitric oxide in the dorsal hippocampus of mice.  

PubMed

In the present study, the possible involvement of nitric oxide (NO) systems in the dorsal hippocampus in nicotine's effect on ethanol-induced amnesia and ethanol state-dependent memory was investigated. Adult male mice were cannulated in the CA1 regions of the dorsal hippocampus and trained on a passive avoidance learning task for memory assessment. We found that pre-training intraperitoneal (i.p.) administration of ethanol (1 g/kg) decreased inhibitory avoidance memory when tested 24 h later. The response induced by pre-training ethanol was significantly reversed by pre-test administration of the drug. Similar to ethanol, pre-test administration of nicotine (0.4 and 0.8 ?g/mouse, intra-CA1) alone and nicotine (0.2, 0.4 and 0.8 ?g/mouse) plus an ineffective dose of ethanol also significantly reversed the amnesia induced by ethanol. Ethanol amnesia was also prevented by pre-test administration of L-arginine (1.2 ?g/mouse, intra-CA1), a NO precursor. Interestingly, an ineffective dose of nicotine (0.2 ?g/mouse) in combination with a low dose of L-arginine (0.8 ?g/mouse) synergistically improved memory performance impaired by ethanol given before training. In contrast, pre-test intra-CA1 microinjection of L-NAME (NG-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (0.4 and 0.8 ?g/mouse), which reduced memory retrieval in inhibitory avoidance task by itself, in combination with an effective dose of nicotine (0.4 ?g/mouse) prevented the improving effect of nicotine on memory impaired by pre-training ethanol. Moreover, intra-CA1 microinjection of L-NAME reversed the L-arginine-induced potentiation of the nicotine response. The results suggest the importance of NO system(s) in the CA1 regions of the dorsal hippocampus for improving the effect of nicotine on the ethanol-induced amnesia. PMID:22698687

Raoufi, N; Piri, M; Moshfegh, A; Shahin, M-S

2012-09-01

182

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

183

Comparative study of the efficacy of ascorbic acid, quercetin, and thiamine for reversing ethanol-induced toxicity.  

PubMed

This study compares the curative effect of three antioxidants-ascorbic acid, quercetin, and thiamine-on ethanol-induced toxicity in rats. Administration of ethanol at a dose of 4 g/kg of body weight/day for 90 days initiated chronic alcohol-induced oxidative stress as shown by increased malondialdehyde level and DNA fragmentation in liver and brain. Ethanol administration also led to a decrease in DNA content. Activities of toxicity marker enzymes-alanine aminotransferase, aspartate aminotransferase, and ?-glutamyltranspeptidase-in liver and serum increased progressively upon ethanol administration. After ethanol administration for 90 days, the efficacy of antioxidant treatment of the alcohol-induced toxicity was studied by supplementing ascorbic acid (200 mg/100 g of body weight/day), quercetin (50 mg/kg of body weight/day), and thiamine (25 mg/kg of body weight/day) for 30 days. These groups were compared with the abstention group (not treated with ethanol). All the alterations induced by alcohol were reduced significantly by the supplementation of antioxidants and also with abstention. The regression by antioxidants was greater that of abstention. Antioxidants significantly reduced the oxidative stress induced by ethanol intoxication, increased membrane integrity, and also increased organ regeneration. Ascorbic acid was shown to be more effective than quercetin and thiamine in treating both hepatotoxicity and neurotoxicity induced by alcohol administration. This may be due to the higher antioxidant potential of ascorbic acid in physiological conditions. PMID:20946019

Ambadath, Vidhya; Venu, Renju Gopal; Madambath, Indira

2010-12-01

184

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. PMID:23697887

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

2013-01-01

185

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. PMID:21367571

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

2011-01-01

186

Hepatitis B  

MedlinePLUS

... sheet on hepatitis A, B, and C. Hepatitis Risk Assessment 5-minute assessment developed by the federal Centers for Disease Control and Prevention that gives you a personalized report of your hepatitis risk NATAP: Hepatitis Recogizing that coinfection with viral hepatitis ...

187

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

188

Biochanin A Gastroprotective Effects in Ethanol-Induced Gastric Mucosal Ulceration in Rats  

PubMed Central

Background Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs. Methodology The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. Conclusions This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level. PMID:25811625

Hajrezaie, Maryam; Salehen, NurAin; Karimian, Hamed; Zahedifard, Maryam; Shams, Keivan; Batran, Rami Al; Majid, Nazia Abdul; Khalifa, Shaden A. M.; Ali, Hapipah Mohd; El-Seedi, Hesham; Abdulla, Mahmood Ameen

2015-01-01

189

Acute toxicity and gastroprotective effect of the Schiff base ligand ¹H-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

190

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

191

Anthocyanins protect against ethanol-induced neuronal apoptosis via GABAB1 receptors intracellular signaling in prenatal rat hippocampal neurons.  

PubMed

Here, we investigated the possible involvement of gamma-aminobutyric acid B1 receptor (GABAB1R) in mediating the protective effects of black soybean anthocyanins against ethanol-induced apoptosis in prenatal hippocampal neurons because GABARs are known to play an important role in the development of central nervous system. Treatments were performed on primary cultures of prenatal rat hippocampal neurons transfected with or without GABAB1R small interfering RNA (siRNA). The results showed that, when ethanol treatment was followed by anthocyanins treatment, cellular levels of proapoptotic proteins such as Bax, activated caspase-3, and cleaved poly (ADP-ribose) polymerase 1 (PARP-1) were decreased, and the cellular level of the antiapoptotic protein Bcl-2 was increased compared to treatment with ethanol alone. Furthermore, the effects of ethanol on cellular levels of GABAB1R and its downstream signaling molecules such as protein kinase A, calcium/calmodulin-dependent protein kinase II (CaMKII), and phosphorylated cAMP response element binding protein were diminished or reversed by anthocyanins treatment. The ability of anthocyanins to reverse the effects of ethanol on cellular levels of Bax, Bcl-2, active caspase-3, cleaved PARP-1, GABAB1R, and CaMKII were abrogated in cells transfected with GABAB1R siRNA. In a GABAB1R-dependent manner, anthocyanins also inhibited the ability of ethanol to elevate intracellular free Ca(2+) level and increase the proportion of cells with low mitochondrial membrane potential in the population. Cell apoptosis assay and morphological studies also confirmed the neuroprotective effect of anthocyanins against ethanol via GABAB1R. Our data suggest that GABAB1R plays an important role in the neuroprotective effects of anthocyanins against ethanol. PMID:23645118

Ali Shah, Shahid; Ullah, Ikram; Lee, Hae Young; Kim, Myeong Ok

2013-08-01

192

Anandamide-CB1 receptor signaling contributes to postnatal ethanol-induced neonatal neurodegeneration, adult synaptic, and memory deficits.  

PubMed

The transient exposure of immature rodents to ethanol during postnatal day 7 (P7), which is comparable with the third trimester in 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 CB1R 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 before ethanol treatment at P7 relieved ERK1/2 but not AKT phosphorylation and prevented neurodegeneration. CB1R knock-out 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. PMID:23575834

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

2013-04-10

193

Unilateral whisker clipping exacerbates ethanol-induced social and somatosensory behavioral deficits in a sex- and age-dependent manner.  

PubMed

Prenatal exposure to ethanol results in sensory deficits and altered social interactions in animal and clinical populations. Sensory stimuli serve as important cues and shape sensory development; developmental exposure to ethanol or sensory impoverishment can impair somatosensory development, but their combined effects on behavioral outcomes are unknown. We hypothesized 1) that chronic prenatal ethanol exposure would disrupt social interaction and somatosensory performance during adolescence, 2) that a mild sensory impoverishment (neonatal unilateral whisker clipping; WC) would have a mildly impairing to sub-threshold effect on these behavioral outcomes, and 3) that the effect of ethanol would be exacerbated by WC. Long-Evans dams were fed a liquid diet containing ethanol or pair-fed with a non-ethanol diet on gestational days (G) 6-G21. Chow-fed control animals were also included. One male and female pup per litter underwent WC on postnatal day (P)1, P3, and P5. Controls were unclipped. Offspring underwent social interaction on P28 or P42, and gap-crossing (GC) on P31 or P42. Ethanol-exposed pups played less and crossed shorter gaps than control pups regardless of age or sex. WC further exacerbated ethanol-induced play fighting and GC deficits in all males but only in 28-day-old females. WC alone reduced sniffing in all males and in younger females. Thus, prenatal ethanol exposure induced deficits in social interaction and somatosensory performance during adolescence. Sensory impoverishment exacerbates ethanol's effect in 28-day-old male and female animals and in 42-day-old males, suggesting sex- and age-dependent changes in outcomes in ethanol-exposed offspring. PMID:25283794

Wellmann, Kristen A; Mooney, Sandra M

2014-10-01

194

Presynaptic BK Channels Modulate Ethanol-Induced Enhancement of GABAergic Transmission in the Rat Central Amygdala Nucleus  

PubMed Central

Large-conductance calcium-activated potassium BK channels are widely expressed in the brain and are involved in the regulation of neuronal functions such as neurotransmitter release. However, their possible role in mediating ethanol-induced GABA release is still unknown. We assessed the role of BK channels in modulating the action of ethanol on inhibitory synaptic transmission mediated via GABAA receptors in the rat central nucleus of the amygdala (CeA). Evoked IPSCs (eIPSCs) mediated by GABAA receptors were isolated from CeA neurons under whole-cell voltage clamp, and their response to selective BK channel antagonists, channel activators, or ethanol was analyzed. Blocking BK channels with the specific BK channel antagonist paxilline significantly increased the mean amplitude of eIPSCs, whereas the activation of BK channels with the channel opener NS1619 reversibly attenuated the mean amplitude of eIPSCs. Ethanol (50 mm) alone enhanced the amplitude of eIPSCs but failed to further enhance eIPSCs in the slices pretreated with paxilline. Bath application of either BK channel blockers significantly increased the frequency of miniature IPSCs (mIPSCs). Similarly, 50 mm ethanol alone also enhanced mIPSC frequency. Increases in mIPSC frequency by either selective BK channel antagonists or ethanol were not accompanied with changes in the amplitude of mIPSCs. Furthermore, following bath application of BK channel blockers for 10 min, ethanol failed to further increase mIPSC frequency. Together, these results suggest that blocking BK channels mimics the effects of ethanol on GABA release and that presynaptic BK channels could serve as a target for ethanol effects in CeA. PMID:25297098

Li, Qiang; Madison, Roger

2014-01-01

195

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

PubMed Central

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

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

2014-01-01

196

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 are ... illness. What extra risks are caused by hepatitis B and hepatitis C infections during pregnancy? Not only ...

197

Autoimmune hepatitis.  

PubMed

Autoimmune hepatitis (AIH) is an inflammatory liver disease that mainly affects females. It is characterized histologically by interface hepatitis, biochemically by increased aspartate and alanine aminotransferase levels, and serologically by the presence of autoantibodies and increased levels of immunoglobulin G. AIH affects both adults and children, and is particularly aggressive in the latter group. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. With appropriate treatment 80% of patients achieve remission and long-term survival. Those patients who progress to end-stage liver disease because they are unresponsive or nonadherent to treatment, and those with fulminant liver failure (encephalopathy grade II-IV) at diagnosis, require liver transplantation. Seropositivity for smooth muscle and/or antinuclear antibodies defines type 1 AIH, while positivity for liver kidney microsomal type 1 antibodies defines type 2 AIH. The primary cause of AIH is unknown; however, considerable knowledge about the mechanisms of liver damage involved has been gathered over the past 30 years, which is likely to provide the basis for specific modes of treatment and a possible cure. PMID:21537351

Mieli-Vergani, Giorgina; Vergani, Diego

2011-06-01

198

Influence of hepatitis G virus coinfection on the clinical course of chronic hepatitis C.  

PubMed

Hepatitis G virus (HGV) is a parenterally transmitted virus, frequently associated with hepatitis C virus infection. Hepatitis G virus RNA was detected by reverse transcription-polymerase chain reaction in the serum of 40 patients with chronic hepatitis C. Nine (22.5%) patients had evidence of hepatitis G virus viraemia. No significant epidemiological or virological differences could be demonstrated between subjects infected with both hepatitis G virus and hepatitis C virus and subjects infected with hepatitis C virus alone. Aminotransferase values were comparable between the two groups, whereas higher levels of cholestatic enzymes (P< 0.001) were reported in the hepatitis G virus/hepatitis C virus-positive patients. A liver biopsy was performed on all 40 patients no later than 6 months before recruitment. The mean histological activity index did not differ between hepatitis G virus-positive and hepatitis G virus-negative patients, whereas specific histological features such as macrovesicular steatosis, portal granulomas, and bile duct damage were more commonly observed among the coinfected patients. The results indicate that coinfection with hepatitis G virus probably does not have a significant effect on hepatitis C virus-induced hepatic damage. PMID:9865984

Cacopardo, B; Berger, A; Cosentino, S; Boscia, V; Vinci, G; Restivo, R; Brancati, G; Russo, R A; Celesia, B M; Patamia, I; Nunnari, A; Doerr, H W

1998-10-01

199

Ethanol-induced analgesia  

SciTech Connect

The effect of ethanol (ET) on nociceptive sensitivity was evaluated using a new tail deflection response (TDR) method. The IP injection of ET (0.5 - 1.5 g/kg) produced raid dose-dependent analgesia. Near maximal effect (97% decrease in TDR) was produced with the 1.5 g/kg dose of ET ten minutes after injection. At ninety minutes post-injection there was still significant analgesia. Depression of ET-induced nociceptive sensitivity was partially reversed by a 1 mg/kg dose of naloxone. On the other hand, morphine (0.5 or 5.0 mg/kg IP) did not modify ET-induced analgesia, while 3.0 minutes of cold water swim (known to produce non-opioid mediated analgesia) potentiated ET-induced analgesic effect. The 0.5 g/kg dose of ET by itself did not depress motor activity in an open field test, but prevented partially the depression in motor activity produced by cold water swim (CWS). Thus, the potentiation by ET of the depression of the TDR produced by CWS cannot be ascribed to the depressant effects of ET on motor activity. 21 references, 4 figures, 1 table.

Pohorecky, L.A.; Shah, P.

1987-09-07

200

Protective role of ellagitannins from Eucalyptus citriodora against ethanol-induced gastric ulcer in rats: impact on oxidative stress, inflammation and calcitonin-gene related peptide.  

PubMed

The gastroprotective activity of an ellagitannin-rich fraction obtained from Eucalyptus citriodora (ECF) was investigated against ethanol-induced gastric ulceration in rats. The rats were pretreated with ECF (25, 50 and 100mg/kg) 1h before the administration of absolute ethanol to induce acute gastric ulceration. The gastric lesions were significantly reduced by all doses of ECF. Notably, pre-treatment with ECF (100mg/kg) conferred 99.6% gastroprotection, which is significantly higher than that produced by omeprazole. Moreover, ECF administration markedly increased the mucin content in a dose-dependent manner. The potent gastroprotective effect of ECF could be partly mediated by attenuating ethanol-induced oxidative stress. ECF-pre-treatment markedly increased the depleted GSH and SOD levels in a dose-dependent manner. Moreover, ECF significantly decreased the elevated MDA tissue levels induced by ethanol administration. The results demonstrated that ECF administration exerted a powerful anti-inflammatory activity as evidenced by the reduction in the pro-inflammatory markers; IL-1?, TNF-?, 5-LO and COX-2. Additionally, the caspase-3 tissue levels were significantly reduced in the groups pre-treated with ECF. These results suggest that ECF could exert a beneficial gastroprotective effect through their antioxidant, anti-inflammatory and anti-apoptotic properties. Furthermore, ECF pre-treatment significantly attenuated the ethanol-induced decrease in CGRP expression, which has a protective role against gastric ulceration. Histopathological examination revealed intact mucosal layer, absence of hemorrhage and necrosis in groups treated with ECF. Ellagitannins were identified as the major active constituents responsible for the marked antioxidant and gastroprotective properties of ECF. The HPLC-PDA-ESI/MS/MS technique was employed to identify the ellagitannins of E. citriodora. PMID:25636864

Al-Sayed, Eman; El-Naga, Reem N

2015-01-15

201

Hepatitis B Vaccine: What You Need to Know  

MedlinePLUS

... die in the United States from cirrhosis or liver cancer caused by hepatitis B. Hepatitis B can cause: ... serious, and can lead to: • liver damage (cirrhosis) • liver cancer • death Chronic infection is more common among infants ...

202

Effect of glyprolines PGP, GP, and PG on homeostasis of gastric mucosa in rats with experimental ethanol-induced gastric ulcers.  

PubMed

The decrease in the severity of erosions and ulcer lesions after preventive treatment with PGP or PG correlated with a decrease in the content of lipid peroxidation products to a control level. Activities of SOD and catalase also returned to control values. GP produced the weakest effect on pro- and antioxidant state of the gastric mucosa. We concluded that the pronounced preventive effect of PGP and PG on the development of ethanol-induced erosions and ulcer lesions is largely determined by their antioxidant properties. Glyprolines can be considered as a promising means for prevention and treatment of stomach and duodenal ulcers. PMID:21165422

Falalyeyeva, T M; Samonina, G E; Beregovaya, T V; Andreeva, L A; Dvorshchenko, E A

2010-11-01

203

miR-497 and miR-302b Regulate Ethanol-induced Neuronal Cell Death through BCL2 Protein and Cyclin D2*  

PubMed Central

In chronic alcoholism, brain shrinkage and cognitive defects because of neuronal death are well established, although the sequence of molecular events has not been fully explored yet. We explored the role of microRNAs (miRNAs) in ethanol-induced apoptosis of neuronal cells. Ethanol-sensitive miRNAs in SH-SY5Y, a human neuroblastoma cell line, were identified using real-time PCR-based TaqMan low-density arrays. Long-term exposure to ethanol (0.5% v/v for 72 h) produced a maximum increase in expression of miR-497 (474-fold) and miR-302b (322-fold). Similar to SH-SY5Y, long-term exposure to ethanol induced miR-497 and miR-302b in IMR-32, another human neuroblastoma cell line. Using in silico approaches, BCL2 and cyclin D2 (CCND2) were identified as probable target genes of these miRNAs. Cotransfection studies with 3?-UTR of these genes and miRNA mimics have demonstrated that BCL2 is a direct target of miR-497 and that CCND2 is regulated negatively by either miR-302b or miR-497. Overexpression of either miR-497 or miR-302b reduced expression of their identified target genes and increased caspase 3-mediated apoptosis of SH-SY5Y cells. However, overexpression of only miR-497 increased reactive oxygen species formation, disrupted mitochondrial membrane potential, and induced cytochrome c release (mitochondria-related events of apoptosis). Moreover, ethanol induced changes in miRNAs, and their target genes were substantially prevented by pre-exposure to GSK-3B inhibitors. In conclusion, our studies have shown that ethanol-induced neuronal apoptosis follows both the mitochondria-mediated (miR-497- and BCL2-mediated) and non-mitochondria-mediated (miR-302b- and CCND2-mediated) pathway. PMID:21878650

Yadav, Sanjay; Pandey, Ankita; Shukla, Aruna; Talwelkar, Sarang S.; Kumar, Ashutosh; Pant, Aditya B.; Parmar, Devendra

2011-01-01

204

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

PubMed Central

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

205

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

206

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. PMID:24302966

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

2013-01-01

207

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

208

ETHANOL INDUCES RAT HEPATIC ALCOHOL DEHYDROGENASE (ADH) CLASS I BY INTERFERING WITH POST-TRANSLATIONAL REGULATION OF STEROL REGULATORY ELEMENT BINDING PROTEIN-1 (SREBP-1)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Continuous infusion of ethanol into the stomach of nutritionally supported rats results in pulses of blood and urine ethanol with a 6-7 day cycle rather than the steady-state normally observed with chronically infused drugs. The cycle is driven by cyclical changes in transcription of liver ADH Class...

209

Hepatitis C  

MedlinePLUS

... 2014 Select a Language: Fact Sheet 507 Hepatitis C WHAT IS HEPATITIS C? HOW IS IT DIAGNOSED? ... treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure ...

210

Hepatitis E  

MedlinePLUS

... non-enveloped, positive-sense, single-stranded ribonucleic acid (RNA) virus. The hepatitis E virus is transmitted mainly ... RT-PCR) to detect the hepatitis E virus RNA in blood and/or stool, but this assay ...

211

Autoimmune hepatitis  

MedlinePLUS

Autoimmune hepatitis is inflammation of the liver that occurs when immune cells mistake the liver's normal cells ... This form of hepatitis is an autoimmune disease . The body's immune ... body tissue and harmful, outside substances. The result is an ...

212

Hepatitis C  

MedlinePLUS

... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

213

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. PMID:23451106

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

2013-01-01

214

[Acute hepatitis in infectious diseases].  

PubMed

Hepatitis A, B, C, D, E, G are the most common causes of acute hepatitis, however, there are many infectious diseases affecting liver and with fever, early diagnostics of which is very important for the clinic of internal diseases. This review presents infections, causing fever and hepatitis, but not necessarily accompanied by jaundice. Leptospirosis, yellow fever have been considered, in which liver damage determines the clinic and the prognosis of the disease. In other cases, such as infectious mononucleosis, cytomegalovirus and herpetic hepatitis, typho-para-typhoid infections, typhoid, pneumonia, some viral diseases, malaria, Legionnaire's disease, hepatitis do not have their independent status and represent one of the important syndromes of a common disease. Modern methods of diagnostics and treatment of these diseases have been described. PMID:24294783

Podymova, S D

2013-01-01

215

CB1-receptor knockout neonatal mice are protected against ethanol-induced impairments of DNMT1, DNMT3A, and DNA methylation.  

PubMed

The significant consequences of ethanol use during pregnancy are neurobehavioral abnormalities involving hippocampal and neocortex malfunctions that cause learning and memory deficits collectively named fetal alcohol spectrum disorder. However, the molecular mechanisms underlying these abnormalities are still poorly understood and therefore warrant systematic research. Here, we document novel epigenetic abnormalities in the mouse model of fetal alcohol spectrum disorder. Ethanol treatment of P7 mice, which induces activation of caspase 3, impaired DNA methylation through reduced DNA methyltransferases (DNMT1 and DNMT3A) levels. Inhibition of caspase 3 activity, before ethanol treatment, rescued DNMT1, DNMT3A proteins as well as DNA methylation levels. Blockade of histone methyltransferase (G9a) activity or cannabinoid receptor type-1 (CB1R), prior to ethanol treatment, which, respectively, inhibits or prevents activation of caspase 3, rescued the DNMT1 and DNMT3A proteins and DNA methylation. No reduction of DNMT1 and DNMT3A proteins and DNA methylation was found in P7 CB1R null mice, which exhibit no ethanol-induced activation of caspase 3. Together, these data demonstrate that ethanol-induced activation of caspase 3 impairs DNA methylation through DNMT1 and DNMT3A in the neonatal mouse brain, and such impairments are absent in CB1R null mice. Epigenetic events mediated by DNA methylation may be one of the essential mechanisms of ethanol teratogenesis. Schematic mechanism of action by which ethanol impairs DNA methylation. Studies have demonstrated that ethanol has the capacity to bring epigenetic changes to contribute to the development of fetal alcohol spectrum disorder (FASD). However, the mechanisms are not well studied. P7 ethanol induces the activation of caspase 3 and impairs DNA methylation through reduced DNA methyltransferases (DNMT1 and DNMT3A) proteins (?). The inhibition or genetic ablation of cannabinoid receptor type-1 or inhibition of histone methyltransferase (G9a) by Bix (-----) or inhibition of caspase 3 activation by Q- quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh) () rescue loss of DNMT1, DNMT3A as well as DNA methylation. Hence, the putative DNMT1/DNMT3A/DNA methylation mechanism may have a potential regulatory role in FASD. PMID:25487288

Nagre, Nagaraja N; Subbanna, Shivakumar; Shivakumar, Madhu; Psychoyos, Delphine; Basavarajappa, Balapal S

2015-02-01

216

Protective effects of green tea polyphenol extracts against ethanol-induced gastric mucosal damages in rats: Stress-responsive transcription factors and MAP kinases as potential targets  

Microsoft Academic Search

There are multiple lines of compelling evidence from epidemiologic and laboratory studies supporting that frequent consumption of green tea is inversely associated with the risk of chronic human diseases including cancer. The chemopreventive and chemoprotective effects of green tea have been largely attributed to antioxidative and anti-inflammatory activities of its polyphenolic constituents, such as epigallocatechin gallate. The present study was

Jeong-Sang Lee; Tae-Young Oh; Young-Kyung Kim; Joo-Hyun Baik; Sung So; Ki-Baik Hahm; Young-Joon Surh

2005-01-01

217

Ethanol Induced Acetylation of Histone at G9a Exon1 and G9a-Mediated Histone H3 Dimethylation leads to Neurodegeneration in Neonatal Mice  

PubMed Central

The transient exposure of immature rodents to ethanol during postnatal day 7 (P7), comparable to a time point within the third trimester of human pregnancy, induces neurodegeneration. However, the molecular mechanisms underlying the deleterious effects of ethanol on the developing brain are poorly understood. In our previous study, we showed that a high dose administration of ethanol at P7 enhances G9a and leads to caspase-3-mediated degradation of dimethylated H3 on lysine 9 (H3K9me2). In this study, we investigated the potential role of epigenetic changes at G9a exon1, G9a-mediated H3 dimethylation on neurodegeneration and G9a-associated proteins in the P7 brain following exposure to a low dose of ethanol. We found that a low dose of ethanol induces mild neurodegeneration in P7 mice, enhances specific acetylation of H3 on lysine 14 (H3K14ace) at G9a exon1, G9a protein levels, augments the dimethylation of H3K9 and H3 lysine 27 (H3K27me2). However, neither dimethylated H3K9 nor K27 underwent degradation. Pharmacological inhibition of G9a activity prior to ethanol treatment prevented H3 dimethylation and neurodegeneration. Further, our immunoprecipitation data suggest that G9a directly associates with DNA methyltransferase (DNMT3A) and methyl-CpG-binding protein 2 (MeCP2). In addition, DNMT3A and MeCP2 protein levels were enhanced by a low dose of ethanol that was shown to induce mild neurodegeneration. Collectively, these epigenetic alterations lead to association of G9a, DNMT3A and MeCP2 to form a larger repressive complex and have a significant role in low dose ethanol-induced neurodegeneration in the developing brain. PMID:24300108

Subbanna, Shivakumar; Nagre, Nagaraja N.; Shivakumar, Madhu; Umapathy, Nagavedi S.; Psychoyos, Delphine; Basavarajappa, Balapal S.

2014-01-01

218

Hepatic disorders in chronic kidney disease  

Microsoft Academic Search

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most common and serious causes of liver damage in patients with chronic kidney disease (CKD). The natural histories of HBV and HCV infections in patients with CKD are not fully understood; however, recent evidence has emphasized the adverse effect of HBV and\\/or HCV infection on survival in this

Piergiorgio Messa; Carlo Basile; Paul Martin; Fabrizio Fabrizi

2010-01-01

219

Lamivudine treatment for severe acute HBV hepatitis  

Microsoft Academic Search

Treatment for acute hepatitis B is recommended in order to reduce the risk of progression to fulminant hepatitis and the need of OLT. We report our experience on treatment with high dose lamivudine, in patients with severe acute HBV infection. The diagnosis was based on clinical and virological findings and exclusion of other known causes of liver damage. The decision

Andrea Lisotti; Francesco Azzaroli; Federica Buonfiglioli; Marco Montagnani; Flavio Alessandrelli; Giuseppe Mazzella

220

Probucol attenuates ethanol-induced liver fibrosis in rats by inhibiting oxidative stress, extracellular matrix protein accumulation and cytokine production.  

PubMed

1. Liver fibrosis is characterized by excessive accumulation of extracellular matrix (ECM) proteins in the liver. Probucol, a lipid-lowering drug, was found to prevent liver injury in rats treated with carbon tetrachloride (CCl4 ). In the present study, we investigated whether probucol has protective effect against liver fibrosis in rats treated with ethanol and CCl4 . 2. Thirty rats were randomly divided into five groups. Groups I and II served as the normal control and the model of liver fibrosis, respectively. Groups III-V were treated with probucol at a doses of 250, 500 and 1000 mg/kg, respectively. Rats in Group II were fed a complex diet that includes alcohol, corn oil and pyrazole, and were injected intraperitoneally with CCl4 to induce hepatic fibrosis. Blood was obtained to assess markers of liver function. Liver samples were collected to evaluate mRNA and protein expression, histological changes and oxidative stress. 3. Probucol significantly attenuated the histological changes induced by ethanol + CCl4 and improved liver function. Expression levels of ?-smooth muscle actin and collagen I was decreased in the probucol-treated groups. Moreover, probucol markedly suppressed increases in oxidative stress, ECM protein accumulation and cytokine production induced by ethanol + CCl4 . Finally, probucol inhibited activation of the extracellular signal-regulated kinase signalling pathway induced by ethanol + CCl4 . 4. Our findings reveal that probucol attenuates ethanol + CCl4 -induced liver fibrosis by inhibiting oxidative stress, ECM protein accumulation and cytokine production. These data suggest that probucol may be useful for the prevention and treatment of hepatic fibrosis. PMID:24117782

Su, Xuesong; Wang, Yanqiu; Zhou, Guangyu; Yang, Xu; Yu, Rui; Lin, Yan; Zheng, Changqing

2014-01-01

221

Hepatitis virus panel  

MedlinePLUS

Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... Blood (serology) tests are used to check for antibodies to each of the hepatitis viruses.

222

Hepatitis C and Incarceration  

MedlinePLUS

... type in jails and prisons. What is Hepatitis C? Hepatitis C is a serious liver disease that ... call this chronic Hepatitis C. Incarceration and Hepatitis C • Hepatitis C can be a health problem for ...

223

Hepatitis B Vaccine  

MedlinePLUS

Engerix-B® ... 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.In ...

224

Hepatitis A  

MedlinePLUS

... Abuse Young Adult: 18-21 yrs. Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Safety & Prevention Immunizations Chickenpox Tdap Haemophilus Influenzae Type B (Hib) Hepatitis A (HepA) Hepatitis B (HepB) Human Papillomavirus (HPV) ...

225

Hepatic hemangiomas  

Microsoft Academic Search

There are 2 main and different forms of hepatic hemangiomas-those of early childhood and those of later adult life. The former, called infantile hepatic hemangioendothelioma, may be life-threatening due to arteriovenous shunting in extensive lesions resulting in cardiac failure. Although they may resolve spontaneously, if cardiac failure develops, they must be treated aggressively by arterial ligation or embolization. The adult

K. E. F. Hobbs

1990-01-01

226

Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis  

PubMed Central

Objective Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. Design Intracellular calcium ([Ca2+]C), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. Results Inhibition of OME with 4-MP converted predominantly transient [Ca2+]C rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. Conclusions A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation. PMID:24162590

Huang, Wei; Booth, David M; Cane, Matthew C; Chvanov, Michael; Javed, Muhammad A; Elliott, Victoria L; Armstrong, Jane A; Dingsdale, Hayley; Cash, Nicole; Li, Yan; Greenhalf, William; Mukherjee, Rajarshi; Kaphalia, Bhupendra S; Jaffar, Mohammed; Petersen, Ole H; Tepikin, Alexei V; Sutton, Robert; Criddle, David N

2014-01-01

227

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. 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

228

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; João 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

229

Immunochemical evidence for an ethanol-inducible form of liver microsomal cytochrome P-450 in rodents and primates  

SciTech Connect

Polyclonal antibodies against cytochrome P-450-4, a major liver microsomal P-450 isozyme purified from ethanol (E)-treated hamsters, were used to probe for immunochemically-related hemeproteins in other species. Liver microsomes (LM) were obtained from naive and E-treated rats, deermice, hamsters, and baboons. Baboon liver 9000 x g supernatant (S-9) was prepared from needle biopsy samples. LM and S-9 proteins were resolved by SDS-PAGE, then transferred to nylon membranes. Immunodetection was performed on the Western blots using rabbit anti P-450-4 IgG, anti-rabbit IgG-alk. phos., and an appropriate chromagen. Control LM from all species contained a cross-reacting protein of mol. wt. similar to P-450-4 (54k). The amount of this cross-reacting protein as reflected by staining intensity, was much higher in LM from E-treated animals. This protein was also detected in S-9 from E-treated baboons. In contrast, no increase in phenobarbital-inducible P-450-2 related LM protein (assessed using anti P-450-2) was observed after E treatment. Increased P-450-4 related protein in LM from E-treated animals was associated with enhanced oxidation of ethanol and aniline by these LM when compared to controls. In conclusion, LM from rats, deermice, and baboons contain a protein immunochemically homologous to hamster liver P-450-4. As observed in hamsters, the amount of this hepatic protein increases in these other species after E treatment.

Lasker, J.M.; Ardies, C.M.; Bloswick, B.P.; Lieber, C.S.

1986-05-01

230

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. PMID:23006457

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

2012-01-01

231

Ethanol-induced changes in the expression of proteins related to neurotransmission and metabolism in different regions of the rat brain.  

PubMed

Despite extensive description of the damaging effects of chronic alcohol exposure on brain structure, mechanistic explanations for the observed changes are just emerging. To investigate regional brain changes in protein expression levels following chronic ethanol treatment, one rat per sibling pair of male Wistar rats was exposed to intermittent (14 h/day) vaporized ethanol, the other to air for 26 weeks. At the end of 24 weeks of vapor exposure, the ethanol group had blood ethanol levels averaging 450 mg%, had not experienced a protracted (> 16 h) withdrawal from ethanol, and revealed only mild evidence of hepatic steatosis. Extracted brains were micro-dissected to isolate the prefrontal cortex (PFC), dorsal striatum (STR), corpus callosum genu (CCg), CC body (CCb), anterior vermis (AV), and anterior dorsal lateral cerebellum (ADLC) for protein analysis with two-dimensional gel electrophoresis. Expression levels for 54 protein spots were significantly different between the ethanol- and air-treated groups. Of these 54 proteins, tandem mass spectroscopy successfully identified 39 unique proteins, the levels of which were modified by ethanol treatment: 13 in the PFC, 7 in the STR, 2 in the CCg, 7 in the CCb, 7 in the AV, and 5 in the ADLC. The functions of the proteins altered by chronic ethanol exposure were predominantly associated with neurotransmitter systems in the PFC and cell metabolism in the STR. Stress response proteins were elevated only in the PFC, AV, and ADLC perhaps supporting a role for frontocerebellar circuitry disruption in alcoholism. Of the remaining proteins, some had functions associated with cytoskeletal physiology (e.g., in the CCb) and others with transcription/translation (e.g., in the ADLC). Considered collectively, all but 4 of the 39 proteins identified in the present study have been previously identified in ethanol gene- and/or protein-expression studies lending support for their role in ethanol-related brain alterations. PMID:21397625

Zahr, Natalie M; Bell, Richard L; Ringham, Heather N; Sullivan, Edith V; Witzmann, Frank A; Pfefferbaum, Adolf

2011-09-01

232

Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults  

MedlinePLUS

Understanding Task Force Recommendations Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults The U.S. ... B infection? Hepatitis B is one of several viruses that can damage the liver. The virus is ...

233

Hepatic Encephalopathy  

MedlinePLUS Videos and Cool Tools

... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ... travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic ...

234

Hepatitis A.  

PubMed

Hepatitis A is a common viral illness worldwide, although the incidence in the United States has diminished in recent years as a result of extended immunization practices. Hepatitis A virus is transmitted through fecal-oral contamination, and there are occasional outbreaks through food sources. Young children are usually asymptomatic, although the likelihood of symptoms tends to increase with age. Most patients recover within two months of infection, although 10 to 15 percent of patients will experience a relapse in the first six months. Hepatitis A virus does not usually result in chronic infection or chronic liver disease. Supportive care is the mainstay of treatment. The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend routine vaccination of all children 12 to 23 months of age, as well as certain vulnerable populations. Hepatitis A vaccine is also recommended for most cases of postexposure prophylaxis, although immunoglobulin is an acceptable alternative in some situations. PMID:23198670

Matheny, Samuel C; Kingery, Joe E

2012-12-01

235

MicroRNA-29b Regulates Ethanol-induced Neuronal Apoptosis in the Developing Cerebellum through SP1/RAX/PKR Cascade*  

PubMed Central

Neuronal loss is a prominent etiological factor for fetal alcohol spectrum disorders. The cerebellum is one of the areas in the developing central nervous system that is most sensitive to ethanol, especially during the temporal window of ethanol vulnerability. MicroRNAs are small, non-coding RNAs capable of regulating diverse cellular functions including apoptosis. Ethanol exposure has been shown to interfere with the expression of microRNAs. However, the role of microRNAs in ethanol neurotoxicity is still not clear. In the present study, we identified a particular microRNA, miR-29b, as a novel target of ethanol in the developing cerebellar granule neurons. We discovered that ethanol exposure suppressed miR-29b and induced neuronal apoptosis. Overexpression of miR-29b rendered neurons protection against ethanol-induced apoptosis. Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade. More importantly, the expression of miR-29b is developmentally regulated, which may account for, at least partially, the temporal window of ethanol sensitivity in the developing cerebellum. PMID:24554719

Qi, Yuanlin; Zhang, Mingfang; Li, Hui; Frank, Jacqueline A.; Dai, Lu; Liu, Huijuan; Chen, Gang

2014-01-01

236

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. PMID:22550543

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

237

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

PubMed

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 E(2) (PGE(2)), 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 PGE(2), SOD and reduced amount of MDA was observed. PMID:22550543

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

238

MicroRNA-29b regulates ethanol-induced neuronal apoptosis in the developing cerebellum through SP1/RAX/PKR cascade.  

PubMed

Neuronal loss is a prominent etiological factor for fetal alcohol spectrum disorders. The cerebellum is one of the areas in the developing central nervous system that is most sensitive to ethanol, especially during the temporal window of ethanol vulnerability. MicroRNAs are small, non-coding RNAs capable of regulating diverse cellular functions including apoptosis. Ethanol exposure has been shown to interfere with the expression of microRNAs. However, the role of microRNAs in ethanol neurotoxicity is still not clear. In the present study, we identified a particular microRNA, miR-29b, as a novel target of ethanol in the developing cerebellar granule neurons. We discovered that ethanol exposure suppressed miR-29b and induced neuronal apoptosis. Overexpression of miR-29b rendered neurons protection against ethanol-induced apoptosis. Furthermore, our data indicated that miR-29b mediated ethanol neurotoxicity through the SP1/RAX/PKR cascade. More importantly, the expression of miR-29b is developmentally regulated, which may account for, at least partially, the temporal window of ethanol sensitivity in the developing cerebellum. PMID:24554719

Qi, Yuanlin; Zhang, Mingfang; Li, Hui; Frank, Jacqueline A; Dai, Lu; Liu, Huijuan; Chen, Gang

2014-04-01

239

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 ...

240

Reduced Expression of DNA Damage Repair Genes High Mobility Group Box1 and Poly(ADP-ribose) Polymerase1 in Inactive Carriers of Hepatitis B Virus Infection-A Possible Stage of Viral Integration  

PubMed Central

Background High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1 (PARP1) proteins repair cellular DNA damage. Reduced expression of the corresponding genes can lead to an impaired DNA damage repair mechanism. Intracellular replication of hepatitis B virus (HBV) in such conditions can favor the integration of viral DNA into host genome leading to the development of hepatocellular carcinoma (HCC). Objective This study was performed to assess the expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV replication intermediate pregenomic RNA (PgRNA) in various phases of HBV infection. Materials Eighty eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n = 15), inactive carriers (IC; n = 36), cirrhosis (Cirr; n = 25) and hepatocellular carcinoma (HCC; n = 12). Serum HBV DNA was quantified by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) and densitometry. Results Significant reduction of HMGB1 and PARP1 gene expressions (P < 0.05) were observed in patients than controls with more explicit decline of PARP1 (P = 0.0002). Both genes were significantly downregulated (P < 0.001) in ICs than controls. In ICs, HMGB1 was significantly lowered than cirrhosis (P = 0.002) and HCC (P = 0.0006) while PARP1 declined significantly (P = 0.04) than HCC. Level of PgRNA was comparable in all the disease categories. Conclusion In conclusion, our findings indicate impaired DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low viral load but higher level of PgRNA in this group is suggestive of the diversion of HBV replication pathway that might facilitate viral DNA integration in to host genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection might appear advantageous to thwart the development of HCC.

Mukherjee, Rathindra M.; Shravanti, Gelli V.; Jakkampudi, Aparna; Kota, Ramya; Jangala, Asha L.; Reddy, Panyala B.; Rao, Padaki N.; Gupta, Rajesh; Reddy, Duvvuru N.

2013-01-01

241

Biphasic effects of histamine on ethanol-induced gastric mucosal lesions: Studies with betahistine, dimaprit, (R). alpha. -methylhistamine and nizatidine  

SciTech Connect

In elucidating further the role that histamine (H) may play in gastroprotection against hemorrhagic mucosal lesions (HML) induced by ethanol (E), fasted S-D rats were treated with subcutaneous (s.c.) H 10, 15, 20 and 30 min before intragastric (i.g.) 100% E or H-agonists betahistine (H1) or dimaprit (H2) i.g. 30 min. before 75% E. All animals were killed 1 hr after E, HML were measured with stereomicrosopic planimetry and expressed as % of glandular stomach. The H2 antagonist nizatidine did not influence the extent of HML. As a follow up to previously reported nizatidine blockade of H2-induced gastroprotection against 75% E, nizatidine + H1 or nizatidine + H3 agonist (R){alpha}-methylhistamine was also tested. The H2 antagonist nizatidine abolished the gastroprotection by H3 but did not influence the H1-induced reduction of HML. H injected s.c. showed a dose- and time-dependent biphasic effect on E-induced gastric mucosal lesions. Both H1- and H2-agonists injected s.c. reduced the E-induced damage. Nizatidine alone failed to influence mucosal lesions, blocked gastroprotection induced by H2 or H3, but not by H1 agonists.

Morales, R.E.; Palitzsch, K.D.; Szabo, S. (Harvard Medical School, Boston, MA (United States))

1991-03-15

242

Biochemical laboratory tests in viral hepatitis and other hepatic diseases  

PubMed Central

The differential diagnosis between viral hepatitis and other liver diseases (particularly obstructive jaundice) is often difficult on purely clinical grounds. Damage to the liver causes changes in the pattern of the serum enzymes and this has led to the development in recent years of a number of enzyme tests. The authors have amassed evidence to show that the most useful of these is determination of the levels of serum glutamic oxalacetic and serum glutamic pyruvic transaminase (SGOT and SGPT), coupled with calculation of the SGOT/SGPT ratio. It is characteristic of viral hepatitis that both levels are greatly increased, but the SGOT/SGPT ratio, normally greater than one, falls considerably below his figure. In a few cases of obstructive jaundice, the serum transaminase picture may initially resemble that in viral hepatitis, but the differential diagnosis can be established by repeating the determinations at intervals. Other enzyme tests, such as determination of alkaline phosphatase and leucylaminopeptidase, may be used to confirm the biliary obstruction. Flocculation tests and electrophoretic determination of the plasma protein picture, while of limited value in the diagnosis of acute viral hepatitis, are useful in conjunction with the serum transaminase test for assessing the activity of the disease and any tendency to progress towards “active” chronic hepatitis or post-hepatic cirrhosis. PMID:14292063

De Ritis, Fernando; Giusti, Giuseppe; Piccinino, Felice; Cacciatore, Luigi

1965-01-01

243

Organ Damage and Hepatic Lipid Accumulation in Carp (Cyprinus carpio L.) after Feed-Borne Exposure to the Mycotoxin, Deoxynivalenol (DON)  

PubMed Central

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

2014-01-01

244

Protective effects of melittin on tumor necrosis factor-? induced hepatic damage through suppression of apoptotic pathway and nuclear factor-kappa B activation.  

PubMed

Melittin, a major polypeptide in honeybee venom, have been used to treat inflammatory disease. Various studies have demonstrated the anti-bacterial, anti-viral, anti-inflammatory and anticancer effects of bee venom and melittin. However, the precise mechanism of melittin in liver disease is not yet known. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis. In the present study, we investigated the anti-apoptotic effect of melittin on tumor necrosis factor (TNF)-?/actinomycin (Act) D-induced apoptosis in hepatocytes. Our results show significant protection from DNA damage by melittin treatment compared with corresponding TNF-?/Act D-treated hepatocytes without melittin. Melittin inhibited TNF-?/Act D-induced activation of the caspase, bcl-2 family of proteins and poly ADP-ribose polymerase (PARP)-1. Our results also indicate that melittin decreased nuclear factor-kappa B (NF-?B) by degradation of phosphorylation of I?B kinase (p-IKK) and NF-?B DNA binding activity in TNF-?/Act D-treated hepatocytes. These results suggest that melittin possesses a potent suppressive effect on apoptotic responses in TNF-?/Act D-treated hepatocytes via the NF-?B pathway. PMID:24872433

Park, Ji-Hyun; Lee, Woo-Ram; Kim, Hyun-Soo; Han, Sang-Mi; Chang, Young-Chae; Park, Kwan-Kyu

2014-12-01

245

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 PMID:11470928

Walsh, K; Alexander, G

2001-01-01

246

[Hepatitis A].  

PubMed

Hepatitis A infection is known since the ancient Chinese, Greek and Roman civilizations but the first documented report was published in the eighteenth century. The hepatovirus belongs to the Picornaviridae family, and carries a single strand RNA. There are 7 genotypes. Antibodies of the IgM and IgA classes, during natural infections, appear early in the serum, together with the first clinical manifestations of the disease, but they may also appear at the end of the first week of infection. There is a spectrum of clinical presentation: asymptomatic infection, symptomatic without jaundice and symptomatic jaundiced. A rare fatal form of hepatitis has been described. Diagnosis of the hepatitis A infection is confirmed by the finding of IgM anti-HAV antibodies, routinely performed using an ELISA test. Treatment is supportive. Intramuscular anti-A gamma globulin is used for passive immune prophylaxis, and there is an efficient vaccine for active immune prophylaxis. PMID:12908041

Pereira, Fausto E L; Gonçalves, Carlos S

2003-01-01

247

Hepatitis C  

NSDL National Science Digital Library

This patient education program explains Hepatitis C, the liver and Hepatitis, symptoms, diagnosis, treatment, risk factors, and prevention. This is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: The tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

Patient Education Institute

248

The cannabinoid receptor 2 agonist, ?-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice.  

PubMed

Several recent studies have suggested that brain CB2 cannabinoid receptors play a major role in alcohol reward. In fact, the implication of cannabinoid neurotransmission in the reinforcing effects of ethanol (EtOH) is becoming increasingly evident. The CB2 receptor agonist, ?-caryophyllene (BCP) was used to investigate the role of the CB2 receptors in mediating alcohol intake and ethanol-induced conditioned place preference (EtOH-CPP) and sensitivity in mice. The effect of BCP on alcohol intake was evaluated using the standard two-bottle choice drinking method. The mice were presented with increasing EtOH concentrations and its consumption was measured daily. Consumption of saccharin and quinine solutions was measured following the EtOH preference tests. Finally, the effect of BCP on alcohol reward and sensitivity was tested using an unbiased EtOH-CPP and loss of righting-reflex (LORR) procedures, respectively. BCP dose-dependently decreased alcohol consumption and preference. Additionally, BCP-injected mice did not show any difference from vehicle mice in total fluid intake in a 24-hour paradigm nor in their intake of graded concentrations of saccharin or quinine, suggesting that the CB2 receptor activation did not alter taste function. More importantly, BCP inhibited EtOH-CPP acquisition and exacerbated LORR duration. Interestingly, these effects were abrogated when mice were pre-injected with a selective CB2 receptor antagonist, AM630. Overall, the CB2 receptor system appears to be involved in alcohol dependence and sensitivity and may represent a potential pharmacological target for the treatment of alcoholism. PMID:24999220

Al Mansouri, Shamma; Ojha, Shreesh; Al Maamari, Elyazia; Al Ameri, Mouza; Nurulain, Syed M; Bahi, Amine

2014-09-01

249

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. PMID:23533604

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

2013-01-01

250

Functional analysis of MADS-box genes controlling ovule development in Arabidopsis using the ethanol-inducible alc gene-expression system.  

PubMed

In Arabidopsis, different combinations of ABC organ identity proteins interact in the presence of SEPALLATA (SEP) proteins to regulate floral organ differentiation. Ectopic expression of SEP3 in combination with class A and B or B and C genes is sufficient to homeotically convert vegetative leaves into petal-like organs and bracts into stamen-like structures, respectively. Recently, it has been shown that the three MADS-box genes SEEDSTICK (STK), SHATTERPROOF1 (SHP1) and SHP2 act redundantly to control ovule identity. Protein interaction assays performed in yeast in combination with genetic studies demonstrated that these MADS-box factors only interact in the presence of SEP proteins to form complexes that determine ovule differentiation. Here, we address the question whether the ectopic co-expression of ovule identity proteins is sufficient to induce the homeotic conversion of vegetative leaves into carpel-like structures bearing ovules. We present the phenotypic characterization of Arabidopsis plants that ectopically express ovule identity factors under the regulation of the ethanol inducible gene expression system. These experiments indicate that the ectopic co-expression of SEP3 and SHP1 and/or STK is probably not sufficient to homeotically transform vegetative tissues into carpels with ovules. However, comparing the phenotypes obtained by ectopic expression of STK and/or SHP1 with or without SEP3 shows that co-expression of factors that are able to form complexes in yeast cause more extreme homeotic transformations, confirming the functional role of these complexes in vivo. PMID:16515858

Battaglia, Raffaella; Brambilla, Vittoria; Colombo, Lucia; Stuitje, Antoine R; Kater, Martin M

2006-04-01

251

Ethanol induced adaptations in 5-HT2c receptor signaling in the bed nucleus of the stria terminalis: implications for anxiety during ethanol withdrawal.  

PubMed

One of the hallmarks of alcohol dependence is the presence of a withdrawal syndrome during abstinence, which manifests as physical craving for alcohol accompanied by subjective feelings of anxiety. Using a model of chronic intermittent ethanol (CIE) vapor in mice, we investigated the role of serotonin2c receptor (5HT2c-R) signaling in the BNST as a neural substrate underlying ethanol-induced anxiety during withdrawal. Mice were subjected to a 5-day CIE regimen of 16 h of ethanol vapor exposure followed by an 8 h "withdrawal" period between exposures. After the 5th and final exposure, mice were withdrawn for 24 h or 1 week before experiments began. Anxiety-like behavior was assessed in the social approach, light dark, and open field tests with mice showing deficits in social, but not general anxiety-like behavior that was alleviated by pretreatment with the 5HT2c-R antagonist SB 242,084 (3 mg/kg, i.p.) 24 h and 1 week post-CIE. Using immunohistochemistry and whole cell patch clamp electrophysiology, we also found that CIE increased FOS-IR and enhanced neuronal excitability in the ventral BNST (vBNST) 24 h into withdrawal in a 5HT2c-R dependent manner. This enhanced excitability persisted for 1 week post-CIE. We also found that mCPP, a 5HT2c/b agonist, induced a more robust depolarization in cells of the vBNST in CIE mice, confirming that 5HT2c-R signaling is upregulated in the vBNST following CIE. Taken together, these results suggest that CIE upregulates 5HT2c-R signaling in the vBNST, leading to increased excitability. This enhanced excitability of the vBNST may drive increased anxiety-like behavior during ethanol withdrawal. PMID:25229718

Marcinkiewcz, Catherine A; Dorrier, Cayce E; Lopez, Alberto J; Kash, Thomas L

2015-02-01

252

Acute Toxicity and Gastroprotection Studies of a New Schiff Base Derived Copper (II) Complex against Ethanol-Induced Acute Gastric Lesions in Rats  

PubMed Central

Background Copper is an essential element in various metabolisms. The investigation was carried out to evaluate acute gastroprotective effects of the Copper (II) complex against ethanol-induced superficial hemorrhagic mucosal lesions in rats. Methodology/Principal Findings Rats were divided into 7 groups. Groups 1 and 2 were orally administered with Tween 20 (10% v/v). Group 3 was orally administered with 20 mg/kg omeprazole (10% Tween 20). Groups 4–7 received 10, 20, 40, and 80 mg/kg of the complex (10% Tween 20), respectively. Tween 20 (10% v/v) was given orally to group 1 and absolute ethanol was given orally to groups 2–7, respectively. Rats were sacrificed after 1 h. Group 2 exhibited severe superficial hemorrhagic mucosal lesions. Gastric wall mucus was significantly preserved by the pre-treatment complex. The results showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histology showed marked reduction of hemorrhagic mucosal lesions in groups 4–7. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. PAS staining of groups 4–7 showed intense stain uptake of gastric mucosa. The acute toxicity revealed the non-toxic nature of the compound. Conclusions/Significance The gastroprotective effect of the Copper (II) complex may possibly be due to preservation of gastric wall mucus; increase in PGE2 synthesis; GSH, SOD, and NO up-regulation of Hsp70 protein; decrease in MDA level; and down-regulation of Bax protein. PMID:23251568

Hassandarvish, Pouya; Gwaram, Nura Suleiman; A. Hadi, A. Hamid; Mohd Ali, Hapipah; Majid, Nazia; Abdulla, Mahmood Ameen

2012-01-01

253

Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection  

PubMed Central

Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8+ T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of “collateral damage” of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8+ T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology. PMID:16565492

Polakos, Noelle K.; Cornejo, Judith C.; Murray, Debbie A.; Wright, Kate O.; Treanor, John J.; Crispe, I. Nicholas; Topham, David J.; Pierce, Robert H.

2006-01-01

254

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. PMID:7834603

Cuthbert, J A

1994-01-01

255

Adenosine: Tipping the balance towards hepatic steatosis and fibrosis  

PubMed Central

Fatty liver is commonly associated with alcohol ingestion and abuse. While the molecular pathogenesis of these fatty changes is well understood, the histochemical 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. PMID:20395005

Robson, Simon C.; Schuppan, Detlef

2010-01-01

256

Relationship between oxidative stress and hepatic glutathione levels in ethanol-mediated apoptosis of polarized hepatic cells  

PubMed Central

AIM: To investigate the role of reactive oxygen species (ROS) in ethanol-mediated cell death of polarized hepatic (WIF-B) cells. METHODS: In this work, WIF-B cultures were treated with pyrazole (inducer of cytochrome P4502E1, CYP2E1) and/or L-buthionine sulfoximine (BSO), a known inhibitor of hepatic glutathione (GSH), followed by evaluation of ROS production, antioxidant levels, and measures of cell injury (apoptosis and necrosis). RESULTS: The results revealed that ethanol treatment alone caused a significant two-fold increase in the activation of caspase-3 as well as a similar doubling in ROS. When the activity of the CYP2E1 was increased by pyrazole pretreatment, an additional two-fold elevation in ROS was detected. However, the CYP2E1-related ROS elevation was not accompanied with a correlative increase in apoptotic cell injury, but rather was found to be associated with an increase in necrotic cell death. Interestingly, when the thiol status of the cells was manipulated using BSO, the ethanol-induced activation of caspase-3 was abrogated. Additionally, ethanol-treated cells displayed enhanced susceptibility to Fas-mediated apoptosis that was blocked by GSH depletion as a result of diminished caspase-8 activity. CONCLUSION: Apoptotic cell death induced as a consequence of ethanol metabolism is not completely dependent upon ROS status but is dependent on sustained GSH levels. PMID:19496190

McVicker, Benita L; Tuma, Pamela L; Kharbanda, Kusum K; Lee, Serene ML; Tuma, Dean J

2009-01-01

257

Hepatitis B virus (image)  

MedlinePLUS

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

258

The influence of the new enkephalin derivative, cyclo[N(?),N(?)-carbonyl-d-Lys(2),Dap(5)] enkephalinamide (cUENK6), on reinstatement of ethanol-induced conditioned place preference in rats.  

PubMed

The aim of the present study was to determine whether a new cyclic analog of enkephalin, cyclo[N(?),N(?)-carbonyl-d-Lys(2),Dap(5)] enkephalinamide (cUENK6), a preferential ?-(MORs), and, to a lower extent, a ?-opioid receptor (DORs) agonist in vitro, could reinstate ethanol-induced conditioned place preference (CPP). In our work, male Wistar rats were first conditioned either with ethanol (10% w/v, 0.5g/kg, intraperitoneally (i.p.)) or 0.9% NaCl in a biased CPP procedure. The intracerebroventricular (i.c.v.) administration of DORs antagonist (naltrindole, 2.5 and 5nmol) or MORs antagonist (?-funaltrexamine, 5 and 10nmol), but not the ? opioid receptor (KORs) antagonist (norbinaltorphimine, 5 and 10nmol) was then administered and inhibited the expression of ethanol-induced CPP. After the extinction session, i.c.v. administration of cUENK6 at the dose of 0.125, 0.25 and 0.5nmol occurred, and was found to reinstate the ethanol-induced CPP similar to that of the priming injection of ethanol. However, the reinstated effect of cUENK6 (0.25nmol) was strongly abolished by administration of naltrindole and, to lesser extent, by ?-funaltrexamine. Furthermore, the preferential MORs agonist-morphine (13nmol, i.c.v.) and the DORs agonist-[Leu(5)]-enkephalin (2.7 and 5.4nmol, i.c.v.) also reinstated the ethanol-induced CPP. cUENK6 given alone at the dose of 0.25nmol before the testing phase had no effect in animals that received 0.9% NaCl during the conditioning phase and also did not influence their locomotor activity. These data suggest that the effects of cUENK6 did not have an impact on the results obtained in the reinstatement procedure of CPP. Overall, the data support the idea that both MORs and DORs are normally involved in the expression and reinstatement of ethanol conditioned seeking behavior - as indexed by CPP in rats. PMID:25817357

Gibula-Bruzda, Ewa; Marszalek-Grabska, Marta; Gawel, Kinga; Witkowska, Ewa; Izdebski, Jan; Kotlinska, Jolanta H

2015-06-01

259

Lesions of the Lateral Habenula Increase Voluntary Ethanol Consumption and Operant Self-Administration, Block Yohimbine-Induced Reinstatement of Ethanol Seeking, and Attenuate Ethanol-Induced Conditioned Taste Aversion  

PubMed Central

The lateral habenula (LHb) plays an important role in learning driven by negative outcomes. Many drugs of abuse, including ethanol, have dose-dependent aversive effects that act to limit intake of the drug. However, the role of the LHb in regulating ethanol intake is unknown. In the present study, we compared voluntary ethanol consumption and self-administration, yohimbine-induced reinstatement of ethanol seeking, and ethanol-induced conditioned taste aversion in rats with sham or LHb lesions. In rats given home cage access to 20% ethanol in an intermittent access two bottle choice paradigm, lesioned animals escalated their voluntary ethanol consumption more rapidly than sham-lesioned control animals and maintained higher stable rates of voluntary ethanol intake. Similarly, lesioned animals exhibited higher rates of responding for ethanol in operant self-administration sessions. In addition, LHb lesion blocked yohimbine-induced reinstatement of ethanol seeking after extinction. Finally, LHb lesion significantly attenuated an ethanol-induced conditioned taste aversion. Our results demonstrate an important role for the LHb in multiple facets of ethanol-directed behavior, and further suggest that the LHb may contribute to ethanol-directed behaviors by mediating learning driven by the aversive effects of the drug. PMID:24695107

Schwager, Andrea L.; Sinclair, Michael S.; Tandon, Shashank; Taha, Sharif A.

2014-01-01

260

Pathogenesis of hepatic encephalopathy  

Microsoft Academic Search

METABOLIC ALTERATIONS IN HEPATIC FAILURE A multitude of changes in metabolic processes occurs with hepatic failure. It is therefore particularly important to distinguish between correlations and causes when considering the pathogenesis of hepatic coma. The etiology appears to be multifactorial. First, to be considered a causative factor, an abnormality must be consistently present when hepatic encephalopathy is present. Second, creation

Leslie Zieve

1987-01-01

261

Prostaglandin protection of rat colonic mucosa from damage induced by ethanol.  

PubMed

The effects of pretreatment with 16,16-dimethyl prostaglandin E2 (dmPGE2) on ethanol-induced colonic damage were studied in the rat. Colonic damage was assessed macroscopically, histologically, and using cytoplasmic (lactate dehydrogenase) and lysosomal (acid phosphatase) enzyme markers of cell disruption. Intrarectal administration of 30% ethanol produced grossly visible regions of hyperemia and hemorrhage. Histologically, the ethanol injury was characterized by complete destruction of the surface epithelium and necrosis extending throughout most of the mucosal layer. When incubated in vitro after challenge with ethanol in vivo, the colons released significantly more acid phosphatase and lactate dehydrogenase than did controls. Intrarectal pretreatment with dmPGE2 caused a dose-dependent reduction in ethanol-induced damage, as measured by all three parameters. A significant (P less than 0.05) reduction of macroscopically visible damage was observed with 0.2 micrograms/kg dmPGE2, while at higher doses (20 micrograms/kg) the histological signs of damage, including that to the colonic epithelium, were reduced or completely prevented. This dose of dmPGE2 also reduced (P less than 0.01) the release of the enzyme-markers to control levels. The possibility that this protection was mediated by increased colonic fluid secretion was studied. Pretreatment with dmPGE2 had no effect on net colonic fluid secretion (measured using the nonabsorbable marker [3H]inulin) or on the absorption of ethanol by the colon. This study demonstrates that intrarectal administration of dmPGE2 can protect the colonic mucosa from damage induced by direct application of a potent topical irritant. With the highest dose of dmPGE2 tested (20 micrograms/kg), protection of the colonic epithelium from ethanol injury was observed. PMID:3875465

Wallace, J L; Whittle, B J; Boughton-Smith, N K

1985-09-01

262

Hepatitis B: Information for Parents  

MedlinePLUS

... 2014 The best way to protect against hepatitis B is by getting the hepatitis B vaccine. Doctors recommend that all children get the vaccine. Why should my child get the hepatitis B shot? The hepatitis B shot: • Protects your child ...

263

Upregulation of Kupffer cell ? 2A-Adrenoceptors and downregulation of MKP-1 mediate hepatic injury in chronic alcohol exposure  

Microsoft Academic Search

Alcohol-induced liver disease is associated with unacceptable morbidity and mortality. When activated, Kupffer cells (KCs), the resident macrophages in the liver, release proinflammatory cytokine TNF-?, a key mediator of hepatic damage. Although chronic alcohol causes increase in norepinephrine (NE) release leading to hepatic dysfunction, the mechanism of NE-induced hepatic injury in chronic alcohol exposure has not been elucidated. This study

Michael A. Ajakaiye; Asha Jacob; Rongqian Wu; Mian Zhou; Youxin Ji; Weifeng Dong; Zhimin Wang; Xiaoling Qiang; Wayne W. Chaung; Jeffrey Nicastro; Gene F. Coppa; Ping Wang

2011-01-01

264

[Hepatic neoductules].  

PubMed

Proliferation of preexisting bile ducts, ductular metaplasia of hepatocytes and proliferation and differentiation of liver stem cells are discussed in the pathogenesis of neoductular structures in the liver. Under the condition of experimental bile duct obstruction and in extrahepatic bile duct stenosis neoductular structures are first the result of proliferation and sprouting of preexisting ducts and cholangioles. Especially in later stages of cholestasis but also in other chronic progredient liver diseases such as chronic alcoholic liver disease and chronic active hepatitis periportal hepatocytes may show a phenotypic shift towards ductular epithelia. In postnatal liver diseases hepatocytes first express keratin 7 and later keratin 19 during ductular transdifferentiation. This is in contrast to embryonal cholangiogenesis. In alpha-1-antitrypsin-deficiency, hemochromatosis, Wilson's disease, and chronic active hepatitis B cellular deposites typically located in hepatocytes such as alpha-1-AT, siderin, copper, HBs-Ag, and HBc-Ag can also be found in neoductular cells close to hepatocytes. These deposites seem to be retained during the ductular transdifferentiation of hepatocytes. Expression of bile duct-type integrin subtypes and TGF beta 1 in neoductular cells are involved in the changing parenchymal/mesenchymal interplay during neoductogenesis, resulting in periductular basal membrane and periductular fibrosis. In FNH the ductular transdifferentiation of hepatocytes is integrated in the histogenesis of micronodules and portal tract equivalents of these tumor-like lesions. Ductular structures in hepatoblastomas and especially in combined hepatocellular and cholangiocarcinomas (CHCC) may reflect the common embryologic derivation of hepatocytes and biliary epithelia. Non-neoplastic liver tissue in resection specimens of our CHCC showed a lower rate of cirrhosis, and a significantly higher Ki 67-LI of neoductular cells compared to liver tissue in resection specimens of HCC and liver metastases. 3 of 10 CHCC had developed in alpha-1-AT-deficiency, in which this protease-inhibitor was predominantly retained in periportal hepatocytes. These findings in non-neoplastic tumor-bearing liver tissue suggest that CHCC include a special histogenic type of primary liver carcinoma which in analogy to some experimental liver tumors might develop from periportal parenchymal cells. PMID:8600693

Fischer, H P; Meybehm, M; Zhou, H; Schoch, J

1995-01-01

265

Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies.  

PubMed

A study from five hepatology units documenting 157 cases of drug-induced hepatitis and a second study from a laboratory of immunology which tested more than 100,000 sera permitted us to establish the frequency of antiorganelle antibodies and their diagnostic value in drug-induced hepatitis. In drug-induced hepatitis caused by a heterogenous group of drugs consisting of ajmaline, aminopterine, isaxonine, isoniazid, perhexiline, phenylbutazone and troleandromycine, antiorganelle antibodies were absent or rare. In drug-induced hepatitis caused by another heterogenous group of drugs, including clometacin, fenofibrate, oxyphenisatin and papaverine, antismooth muscle, antinucleus and antimitochondria antibodies were found in isolation or in different combinations in 70% of cases. From the presence of antismooth muscle antibodies in sera, we could trace 30 cases of clometacin-induced hepatitis. The third group included drug-induced hepatitis with special antibody:iproniazid-induced hepatitis with antimitochondrial antibody 6 and tienilic acid (ticrynafen)-induced hepatitis with antiliver/kidney microsome antibody 2 (anti-LKM2). These two antibodies are rare in routine sera and were absent in patients who received the drug and had no liver damage. From the presence of corresponding antibodies, we detected six cases of iproniazid-induced hepatitis and 67 cases of tienilic acid-induced hepatitis. Antiorganelle antibodies found in high titers disappeared in 2 to 24 months following withdrawal of the offending drug. The fourth group was represented by halothane-induced hepatitis; antiliver/kidney microsome antibody 1 was weak and infrequent. Similarities between drug-induced hepatitis of the second group and lupoïd hepatitis suggest that drugs may reveal this spontaneous disorder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4029887

Homberg, J C; Abuaf, N; Helmy-Khalil, S; Biour, M; Poupon, R; Islam, S; Darnis, F; Levy, V G; Opolon, P; Beaugrand, M

1985-01-01

266

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. PMID:23866830

2013-01-01

267

Hepatitis C.  

PubMed

Hepatitis C virus (HCV) infection is a major health problem worldwide. The effects of chronic infection include cirrhosis, end-stage liver disease, and hepatocellular carcinoma. As a result of shared routes of transmission, co-infection with HIV is a substantial problem, and individuals infected with both viruses have poorer outcomes than do peers infected with one virus. No effective vaccine exists, although persistent HCV infection is potentially curable. The standard of care has been subcutaneous interferon alfa and oral ribavirin for 24-72 weeks. This treatment results in a sustained virological response in around 50% of individuals, and is complicated by clinically significant adverse events. In the past 10 years, advances in HCV cell culture have enabled an improved understanding of HCV virology, which has led to development of many new direct-acting antiviral drugs that target key components of virus replication. These direct-acting drugs allow for simplified and shortened treatments for HCV that can be given as oral regimens with increased tolerability and efficacy than interferon and ribavirin. Remaining obstacles include access to appropriate care and treatment, and development of a vaccine. PMID:25687730

Webster, Daniel P; Klenerman, Paul; Dusheiko, Geoffrey M

2015-03-21

268

Protect Yourself from Hepatitis  

MedlinePLUS

... a completely different disease. Flu is caused by viruses that attack your lungs and respiratory system; hepatitis ... leave you needing a new liver. Several different viruses—named the hepatitis A, B, C, D and ...

269

Hepatitis C: Treatment  

MedlinePLUS

... C virus ribonucleic acid level or hepatitis C RNA level) This test measures the amount of hepatitis ... in Drug/Alcohol Recovery Alcoholics Anonymous A.A. World Services, Inc. P.O. Box 459 New York, ...

270

Hepatitis and Asian Americans  

MedlinePLUS

... hepatitis/Statistics/2010Surveillance/index.htm At a glance - Immunization of Adults (Hepatitis B) Percentage of adults ages ... stats-surv/nhis/default.htm At a glance – Immunization of Adolescents, aged 13 to 15 years old ( ...

271

Hepatitis B (HBV)  

MedlinePLUS

... for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & ... Dealing With Anger Hepatitis B (HBV) KidsHealth > Teens > Sexual Health > STDs & Other Infections > Hepatitis B (HBV) Print A ...

272

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,

273

Quantification of hepatic FOXP3+ T-lymphocytes in HIV/hepatitis C coinfection.  

PubMed

Coinfection with HIV adversely impacts every stage of hepatitis C (HCV) infection. Liver damage in HCV infection results from host antiviral responses rather than direct viral pathogenesis. Despite depressed cellular immunity, coinfected patients show accelerated hepatic fibrosis compared with HCV monoinfected patients. This paradox is poorly understood. T-regulatory (Treg) cells (CD4+ and FOXP3+) are hypothesized to limit hepatic damage in HCV. Our hypothesis was that reduced frequency of hepatic Treg in HIV/HCV coinfection compared with HCV monoinfection may explain poorer outcomes. We quantified FOXP3+, CD4+, CD8+ and CD20+ cells in liver biopsies of 35 male subjects matched by age and ISHAK fibrosis score, 12 HIV monoinfected, 11 HCV monoinfected and 12 HIV/HCV coinfected. Cell counts were performed using indirect immunohistochemical staining and light microscopy. HIV/HCV coinfected subjects had fewer hepatic FOXP3+ (P = 0.031) and CD4+ cells (P = 0.001) than HCV monoinfected subjects. Coinfected subjects had more hepatic CD8+ cells compared with HCV monoinfected (P = 0.023), and a lower ratio of FOXP3+ to CD8+ cells (0.08 vs 0.27, P < 0.001). Multivariate analysis showed number of CD4+ cells controlled for differences in number of FOXP3+ cells. Fewer hepatic FOXP3+ and CD4+ cells in HIV/HCV coinfection compared with HCV monoinfection suggests lower Treg activity, driven by an overall loss of CD4+ cells. Higher number of CD8+ cells in HIV/HCV coinfection suggests higher cytotoxic activity. This may explain poorer outcomes in HIV/HCV coinfected patients and suggests a potential mechanism by which highly active antiretroviral therapy may benefit these patients. PMID:24597693

Williams, S K; Donaldson, E; Van der Kleij, T; Dixon, L; Fisher, M; Tibble, J; Gilleece, Y; Klenerman, P; Banham, A H; Howard, M; Webster, D P

2014-04-01

274

Chronic alcohol-induced hepatic insulin resistance and ER stress ameliorated by PPAR-? agonist treatment  

PubMed Central

Background Chronic alcoholic liver disease is associated with hepatic insulin resistance, dysregulated lipid metabolism with increased toxic lipid (ceramide) accumulation, lipid peroxidation, and oxidative and endoplasmic reticulum (ER) stress. Peroxisome-proliferator activated receptor (PPAR) agonists are insulin sensitizers that can restore hepatic insulin responsiveness in both alcohol and non-alcohol-related steatohepatitis. Herein, we demonstrate that treatment with a PPAR-? agonist enhances insulin signaling and reduces the severities of ER stress and ceramide accumulation in an experimental model of ethanol-induced steatohepatitis. Methods Adult male Long Evans rats were pair fed with isocaloric liquid diets containing 0% or 37% ethanol (caloric) for 8 weeks. After 3 weeks on the diets, rats were treated with vehicle or PPAR-? agonist twice weekly by i.p. injection. Results Ethanol-fed rats developed steatohepatitis with inhibition of signaling through the insulin and insulin-like growth factor-1 receptors, and Akt activated pathways. Despite continued ethanol exposure, PPAR-? agonist co-treatments increased Akt activation, reduced multiple molecular indices of ER stress and steatohepatitis. Conclusions These results suggest that PPAR-? agonist rescue of chronic alcoholic liver disease is mediated by enhancement of insulin signaling through Akt/metabolic pathways that reduce lipotoxicity and ER stress. PMID:22988930

Ramirez, Teresa; Tong, Ming; Cy Chen, William; Nguyen, Quynh-Giao; Wands, Jack R.; de la Monte, Suzanne M.

2014-01-01

275

Alcoholic hepatitis.  

PubMed

Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (< 84 days after diagnosis), patients with AH were likely to die from liver-related events and infections. In the long-term (? 84 days after diagnosis), those who developed cirrhosis mainly died from liver-related causes, and those who did not develop cirrhosis mainly died from causes related to alcohol abuse. In conclusion, the present thesis provides novel warranted epidemiological information about AH that shows increasing incidence and mortality rates. Consequently, it reiterates the fact that AH is a life-threatening disease and suggests that AH is an increasing public health concern. The most widely used prognostic models may be helpful adjuvants in the routine management of patients with AH, provided that clinicians are aware of the models' limitations. The causes of death in AH are primarily due to liver-related complications, suggesting that patients with AH could benefit from continued follow-up by a hepatologist after the acute episode. PMID:25283626

Damgaard Sandahl, Thomas

2014-10-01

276

Glutathione S-transferase A1 (GSTA1) release, an early indicator of acute hepatic injury in mice.  

PubMed

Three acute hepatic injury models (a CCl4-induced model, APAP-induced model and ethanol-induced model) in mice were used to study the importance of GSTA1 in acute hepatic injury by comparison with a standard enzyme marker, alanine aminotransferase (ALT). GSTA1 release was demonstrated to be an earlier and more sensitive indicator of hepatotoxicity than was ALT. Significant increases in GSTA1 were detected at 2 h after CCl4 exposure, while ALT was undetected at this time. GSTA1 was also a more sensitive indicator of hepatotoxicity than ALT after 6 h. In the APAP and ethanol models, GSTA1 was markedly increased earlier than ALT, at 2 h post exposure. The release of GSTA1 was significantly increased at a dose of 12.5 mg/kg (CCl4 model), 100 mg/kg (APAP model) and 10 ml/kg (ethanol model), the lowest exposure concentration for each model. In contrast, AST release was not statistically significant. These results suggest that GSTA1 can be detected at low concentrations during the early stages of acute hepatic injury and that GSTA1 is a more sensitive and more accurate indicator than ALT. PMID:24964013

Liu, Fangping; Lin, Yuexia; Li, Zhi; Ma, Xin; Han, Qing; Liu, Yingshu; Zhou, Qiong; Liu, Jingli; Li, Rui; Li, Jichang; Gao, Li

2014-09-01

277

Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention  

MedlinePLUS

... Branch in NIDDK's Division of Digestive Diseases and Nutrition. "Today it is clear that hepatitis C is the most common cause of chronic liver disease in the United States, the most common cause ...

278

Feature Hepatitis: Hepatitis Can Strike Anyone  

MedlinePLUS

... please turn Javascript on. From Hollywood's "Walk of Stars" to Main Street, USA, people from all walks ... that includes many well-known names: Legendary television star Larry Hagman was diagnosed with advanced hepatitis C ...

279

Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis  

Microsoft Academic Search

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients.

D. Keith George; Stefano Goldwurm; Graeme A. Macdonald; Lex L. Cowley; Neal I. Walker; Patrick J. Ward; Elizabeth C. Jazwinska; Lawrie W. Powell

1998-01-01

280

Viral Hepatitis: A through E and Beyond  

MedlinePLUS

... through E and Beyond | Share External Link Disclaimer Liver Disease Viral Hepatitis: A through E and Beyond Alternate Versions ? PDF Version? (139 KB) Additional Links ? Autoimmune Hepatitis Hepatitis A Hepatitis B Hepatitis C Contact Us Digestive Disease Information Phone: ...

281

Hepatic vascular tumors.  

PubMed

The most common hepatic vascular tumor in the pediatric population is the infantile hepatic hemangioma. Although these lesions have a spectrum of presentations, there are three main subtypes that have been described-focal, multifocal, and diffuse. An algorithm on the workup, treatment, and follow-up of these lesions can be based on this categorization. Recent shifts in the management of hemangiomas with beta-blockers (propranolol) have also influenced the treatment of hepatic hemangiomas. This article reviews the current understanding of hepatic hemangiomas and protocols in the management of these patients. PMID:25241093

Hsi Dickie, Belinda; Fishman, Steven J; Azizkhan, Richard G

2014-08-01

282

Isozyme-specific monoclonal antibody-directed assessment of induction of hepatic cytochrome p-450 by clotrimazole.  

PubMed

Clotrimazole, an N-substituted imidazole widely used as an antifungal agent, has been shown to both inhibit and induce hepatic cytochrome P-450 and related monooxygenase activities. In this study the profile of hepatic cytochrome P-450 isozyme(s) induced by clotrimazole treatment of male Sprague-Dawley rats was investigated. Clotrimazole administration (100 mg/kg, daily for 4 days, ig) resulted in 86% induction of spectrally detectable cytochrome P-450 in hepatic microsomes. In these microsomes 7-ethoxycoumarin O-deethylase (126%), aminopyrine N-demethylase (176%), benzphetamine N-demethylase (117%), p-nitrophenol hydroxylase (89%), and 7-ethoxyresorufin O-deethylase (62%) activities were significantly induced, whereas aryl hydrocarbon hydroxylase activity remained unchanged. Characterization of cytochrome P-450 isozyme(s) in hepatic microsomes prepared from clotrimazole-treated animals was based on the immunoreactivity of these microsomes with highly specific monoclonal antibodies (MAbs) raised against 3-methylcholanthrene-specific P-450 (MAb 1-7-1), phenobarbital-specific P-450 (MAb 2-66-3), pregnenolone-16 alpha-carbonitrile-specific P-450 (MAb C2), and ethanol-inducible P-450 (MAb 1-98-1). Western blot analysis of hepatic microsomes prepared from clotrimazole-treated animals with MAb 2-66-3, MAb 1-98-1, and MAb C2 revealed strong immunoreactive bands, whereas moderate reactivity was observed with MAb 1-7-1. MAb 2-66-3 significantly inhibited 7-ethoxycoumarin O-deethylase activity 45%), whereas MAb 1-7-1 moderately inhibited 7-ethoxyresorufin O-deethylase activity (-30%) in clotrimazole-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2571472

Khan, W A; Kuhn, C; Merk, H F; Park, S S; Gelboin, H V; Bickers, D R; Mukhtar, H

1989-01-01

283

Hepatitis A Vaccine  

MedlinePLUS

... the disease to others within the same household.Hepatitis A can cause: ''flu-like'' illness jaundice (yellow skin or eyes, dark urine) severe stomach pains and diarrhea (children) People with hepatitis A often have to be hospitalized (up to about ...

284

Novel hepatitis B vaccines  

Microsoft Academic Search

Currently available hepatitis B vaccines are immunogenic, efficacious and safe. There is no doubt that their consistent use makes the elimination of hepatitis B in most countries possible. Nevertheless, there are still aspects of these vaccines which could be improved: three doses are needed for a full course of vaccination (which is sometimes difficult to achieve because of poor compliance

Wolfgang Jilg

1998-01-01

285

Primary hepatic lymphoma in a patient with chronic hepatitis C.  

PubMed

The case is presented of a woman with chronic active hepatitis C who developed primary hepatic lymphoma. The possible roles of viral hepatitis and therapeutic interferon in the pathogenesis and progression of this unusual malignancy are discussed. In addition, the importance of accurate tissue diagnosis to identify potentially treatable hepatic tumours is emphasized. PMID:8054534

Ryan, J; Wallace, S; Jones, P; Taggart, G; Dudley, F

1994-01-01

286

Hepatitis G virus  

PubMed Central

A number of new hepatitis viruses (G, TT, SEN) were discovered late in the past century. We review the data available in the literature and our own findings suggesting that the new hepatitis G virus (HGV), disclosed in the late 1990s, has been rather well studied. Analysis of many studies dealing with HGV mainly suggests the lymphotropicity of this virus. HGV or GBV-C has been ascertained to influence course and prognosis in the HIV-infected patient. Until now, the frequent presence of GBV-C in coinfections, hematological diseases, and biliary pathology gives no grounds to determine it as an “accidental tourist” that is of no significance. The similarity in properties of GBV-C and hepatitis C virus (HCV) offers the possibility of using HGV, and its induced experimental infection, as a model to study hepatitis C and to develop a hepatitis C vaccine. PMID:18720531

Reshetnyak, Vasiliy Ivanovich; Karlovich, Tatiana Igorevna; Ilchenko, Ljudmila Urievna

2008-01-01

287

Moderate, chronic ethanol feeding exacerbates carbon tetrachloride–induced hepatic fibrosis via hepatocyte-specific hypoxia-inducible factor 1?  

PubMed Central

The hypoxia-sensing transcriptional factor HIF1? is implicated in a variety of hepato-pathological conditions; however, the contribution of hepatocyte-derived HIF1? during progression of alcoholic liver injury is still controversial. HIF1? induces a variety of genes including those involved in apoptosis via p53 activation. Increased hepatocyte apoptosis is critical for progression of liver inflammation, stellate cell activation, and fibrosis. Using hepatocyte-specific HIF1?-deficient mice (?HepHIF1??/?), here we investigated the contribution of HIF1? to ethanol-induced hepatocyte apoptosis and its role in amplification of fibrosis after carbon tetrachloride (CCl4) exposure. Moderate ethanol feeding (11% of kcal) induced accumulation of hypoxia-sensitive pimonidazole adducts and HIF1? expression in the liver within 4 days of ethanol feeding. Chronic CCl4 treatment increased M30-positive cells, a marker of hepatocyte apoptosis in pair-fed control mice. Concomitant ethanol feeding (11% of kcal) amplified CCl4-induced hepatocyte apoptosis in livers of wild-type mice, associated with elevated p53K386 acetylation, PUMA expression, and Ly6c+ cell infiltration. Subsequent to increased apoptosis, ethanol-enhanced induction of profibrotic markers, including stellate cell activation, collagen 1 expression, and extracellular matrix deposition following CCl4 exposure. Ethanol-induced exacerbation of hepatocyte apoptosis, p53K386 acetylation, and PUMA expression following CCl4 exposure was attenuated in livers of ?HepHIF1??/? mice. This protection was also associated with a reduction in Ly6c+ cell infiltration and decreased fibrosis in livers of ?HepHIF1??/? mice. In summary, these results indicate that moderate ethanol exposure leads to hypoxia/HIF1?-mediated signaling in hepatocytes and induction of p53-dependent apoptosis of hepatocytes, resulting in increased hepatic fibrosis during chronic CCl4 exposure. PMID:25089199

Roychowdhury, Sanjoy; Chiang, Dian J; McMullen, Megan R; Nagy, Laura E

2014-01-01

288

Right Hemisphere Brain Damage  

MedlinePLUS

Right Hemisphere Brain Damage [ en Español ] 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 (RHD) is damage ...

289

Sun Damage  

MedlinePLUS

... Keratosis (Solar Keratosis) Actinic keratoses, also known as solar keratoses, are small rough or scaly areas of skin due to damage from sun exposure. Some actinic keratoses can turn into squamous cell skin cancer, so it is important to perform… ...

290

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...

291

Hepatitis B Vaccination Protection  

MedlinePLUS

... an exposure control plan and implement use of universal precautions and control measures, such as engineering controls, ... cost to the worker and at a reasonable time and place. The hepatitis B vaccination is a ...

292

Hepatitis B Foundation  

MedlinePLUS

... Foundation Top Stories Institute Assembles Team of 'All-Star Researchers' to Cure Hepatitis B March 30– The ... Blumberg Institute has recruited a team of “all Star researchers” who will focus exclusively on developing a ...

293

What Is Hepatitis?  

MedlinePLUS

... ??????? Español RSS Feed Youtube Twitter Facebook Google + iTunes Play Store What is hepatitis? Online Q&A ... Twitter WHO Facebook page WHO Google+ page WHO iTunes WHO Play Store © WHO 2015 Back to top ...

294

Hepatitis A FAQs  

MedlinePLUS

... can live outside the body for months. High temperatures, such as boiling or cooking food or liquids ... F (85°C), kill the virus, although freezing temperatures do not. Symptoms Does Hepatitis A cause symptoms? ...

295

Travelers' Health: Hepatitis B  

MedlinePLUS

... transmitted and take measures to minimize their exposures. Map 3-04. Prevalence of chronic hepatitis B virus infection among adults 1,2 View Larger Map PDF Version (printable) 1 Used with permission from: ...

296

Travelers' Health: Hepatitis A  

MedlinePLUS

... INFECTIOUS AGENT Hepatitis A virus (HAV) is an RNA virus classified as a picornavirus. TRANSMISSION Through direct ... months after infection. EPIDEMIOLOGY Common throughout the developing world, where infections most frequently are acquired during early ...

297

Solitary Hepatic Lymphangioma  

PubMed Central

Hepatic lymphangiomas are extremely rare; moreover cystic lymphangiomas usually arise in areas such as the neck and axilla, where loose connective tissue allows the expansion of lymphatic channels. The case of a 65-year old male is described, who presented with a solitary lymphangioma in the liver. The lesion was discovered incidentally and due to diagnostic uncertainty was removed surgically. A short review of histology, clinical presentation and preoperative diagnostic difficulties of hepatic lymphangiomas is given. PMID:7993862

Stavropoulos, M.; Vagianos, C.; Scopa, C. D.; Dragotis, C.; Androulakis, J.

1994-01-01

298

[Hepatic encephalopathy: recent developments].  

PubMed

Hepatic encephalopathy is a neurological syndrome occurring in patients with liver failure or in those with a large porto-systemic shunt. In cirrhotic patients, the current classification comprises covert and overt encephalopathy. Diagnosis of covert encephalopathy requires sensitive tests. Lactulose and rifaximin are the two leading therapeutic options. Rifaximin is efficacious for maintaining remission from hepatic encephalopathy. Liver transplantation should be discussed in cirrhotic patients with encephalopathy. PMID:25277000

Deltenre, Pierre; Moradpour, Darius

2014-09-01

299

All Kids Need Hepatitis B Shots  

MedlinePLUS

... immunize.org action coalition I All kids need hepatitis B shots! A series of shots can prevent ... got infected with hepatitis B virus What is hepatitis B? How do children and teens get hepatitis ...

300

The anticancer drug ellipticine activated with cytochrome P450 mediates DNA damage determining its pharmacological efficiencies: studies with rats, Hepatic Cytochrome P450 Reductase Null (HRN™) mice and pure enzymes.  

PubMed

Ellipticine is a DNA-damaging agent acting as a prodrug whose pharmacological efficiencies and genotoxic side effects are dictated by activation with cytochrome P450 (CYP). Over the last decade we have gained extensive experience in using pure enzymes and various animal models that helped to identify CYPs metabolizing ellipticine. In this review we focus on comparison between the in vitro and in vivo studies and show a necessity of both approaches to obtain valid information on CYP enzymes contributing to ellipticine metabolism. Discrepancies were found between the CYP enzymes activating ellipticine to 13-hydroxy- and 12-hydroxyellipticine generating covalent DNA adducts and those detoxifying this drug to 9-hydroxy- and 7-hydroellipticine in vitro and in vivo. In vivo, formation of ellipticine-DNA adducts is dependent not only on expression levels of CYP3A, catalyzing ellipticine activation in vitro, but also on those of CYP1A that oxidize ellipticine in vitro mainly to the detoxification products. The finding showing that cytochrome b5 alters the ratio of ellipticine metabolites generated by CYP1A1/2 and 3A4 explained this paradox. Whereas the detoxification of ellipticine by CYP1A and 3A is either decreased or not changed by cytochrome b5, activation leading to ellipticine-DNA adducts increased considerably. We show that (I) the pharmacological effects of ellipticine mediated by covalent ellipticine-derived DNA adducts are dictated by expression levels of CYP1A, 3A and cytochrome b5, and its own potency to induce these enzymes in tumor tissues, (II) animal models, where levels of CYPs are either knocked out or induced are appropriate to identify CYPs metabolizing ellipticine in vivo, and (III) extrapolation from in vitro data to the situation in vivo is not always possible, confirming the need for these animal models. PMID:25547492

Stiborová, Marie; ?erná, V?ra; Moserová, Michaela; Mrízová, Iveta; Arlt, Volker M; Frei, Eva

2015-01-01

301

The Anticancer Drug Ellipticine Activated with Cytochrome P450 Mediates DNA Damage Determining Its Pharmacological Efficiencies: Studies with Rats, Hepatic Cytochrome P450 Reductase Null (HRN™) Mice and Pure Enzymes  

PubMed Central

Ellipticine is a DNA-damaging agent acting as a prodrug whose pharmacological efficiencies and genotoxic side effects are dictated by activation with cytochrome P450 (CYP). Over the last decade we have gained extensive experience in using pure enzymes and various animal models that helped to identify CYPs metabolizing ellipticine. In this review we focus on comparison between the in vitro and in vivo studies and show a necessity of both approaches to obtain valid information on CYP enzymes contributing to ellipticine metabolism. Discrepancies were found between the CYP enzymes activating ellipticine to 13-hydroxy- and 12-hydroxyellipticine generating covalent DNA adducts and those detoxifying this drug to 9-hydroxy- and 7-hydroellipticine in vitro and in vivo. In vivo, formation of ellipticine-DNA adducts is dependent not only on expression levels of CYP3A, catalyzing ellipticine activation in vitro, but also on those of CYP1A that oxidize ellipticine in vitro mainly to the detoxification products. The finding showing that cytochrome b5 alters the ratio of ellipticine metabolites generated by CYP1A1/2 and 3A4 explained this paradox. Whereas the detoxification of ellipticine by CYP1A and 3A is either decreased or not changed by cytochrome b5, activation leading to ellipticine-DNA adducts increased considerably. We show that (I) the pharmacological effects of ellipticine mediated by covalent ellipticine-derived DNA adducts are dictated by expression levels of CYP1A, 3A and cytochrome b5, and its own potency to induce these enzymes in tumor tissues, (II) animal models, where levels of CYPs are either knocked out or induced are appropriate to identify CYPs metabolizing ellipticine in vivo, and (III) extrapolation from in vitro data to the situation in vivo is not always possible, confirming the need for these animal models. PMID:25547492

Stiborová, Marie; ?erná, V?ra; Moserová, Michaela; Mrízová, Iveta; Arlt, Volker M.; Frei, Eva

2014-01-01

302

Life Driven by Damaged Damage  

NASA Astrophysics Data System (ADS)

Although life is destined to be approximately described as aself-referential form, the self-reference is invalidated and life avoids a contradiction. Since life does not include any contradiction, it reveals a unity as a whole. Since life is not a self-circulation, it implements diversity and evolvability. Here we show life as invalidated self-reference by constructing a model cell driven by damaged damage. Since life is always close to destruction, it exhibits both of the amoebic motion and the intelligent Physarum-like behavior.

Gunji, Y.-P.; Shirakawa, T.; Niizato, T.; Haruna, T.; Balaz, I.

303

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease  

SciTech Connect

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: 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.

Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China) [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China)] [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)] [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China) [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

2014-01-03

304

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. PMID:24888604

2014-01-01

305

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. PMID:24829586

Heiat, Mohammad; Ranjbar, Reza; Alavian, Seyed Moayed

2014-01-01

306

Endothelium attenuates ethanol induced vasoconstriction of arteries  

SciTech Connect

The authors have previously demonstrated that clinically relevant doses of ethanol (ETH) caused significant vasoconstriction of rabbit thoracic aorta. This study examined the role of endothelium in ethanol vasoconstriction. Thoracic aorta was harvested from 3 New Zealand White rabbits after anesthetization with sodium pentobarbital. Twelve aortic 3 mm rings were mounted in organ baths attached to force transducers and recording apparatus. Six of the twelve rings were denuded. Denudation was confirmed by challenge with acetylcholine (10-4 M). Resting tension was set at 10 grams and the rings equilibrated in 37 C Krebs-Heinsleit solution for 2 hours. Then, the response to norepinephrine (NE) was established (10-8 to 10-5 M). After reattaining resting tension, the response to ETH (500-2,500 ug/ml) was recorded. ETH produced significant vasoconstriction in both non-denuded (48{plus minus}7% of NE max) and denuded (58{plus minus}2% of NE max) arteries. Vasoconstriction was significantly higher in the denuded condition. The authors conclude that the predominant ETH action on arteries is based in vascular smooth muscle although endothelium acts to attenuate the ETH induced vasoconstrictor response.

Morley, D.; Bove, A.A.; Walter, J. (Temple School of Medicine, Philadelphia, PA (United States))

1990-02-26

307

Ethanol Induced Shortening of DNA in Nanochannels  

NASA Astrophysics Data System (ADS)

The confinement of DNA in nanochannels has greatly facilitated the study of DNA polymer physics and holds promise as a powerful tool for genomic sequencing. Ethanol precipitation of DNA is a common tool in molecular biology, typically in >70% [EtOH]. Even at lower ethanol concentrations, however, DNA transforms from B-form to A-form, a shorter yet slightly less twisted conformation. Accordingly, we isolated individual YOYO-1 labeled ?-DNA molecules in 100nmx100nm channels in 0, 20, 40 and 60% [EtOH]. We observed a dramatic shortening in the mean measured lengths with increasing [EtOH] and a broadening of the distribution of measured lengths at the intermediate concentrations. These observed lengths are less than those expected from fully A-form ?-DNA, suggesting that poor solvency effects are involved. Also, substantial spatial variations in intensity in a small number of molecules at the higher [EtOH] suggest the presence of higher order DNA conformations, in accord with the observation that the effective persistence length of DNA has been greatly reduced.

Gemmen, Greg; Reisner, Walter; Tegenfeldt, Jonas; Linke, Heiner

2010-03-01

308

[Liver damage and celiac disease].  

PubMed

Celiac disease (CD) is an important cause of serum aminotransferase elevation: between 5 and 10% of patients with persistent and cryptogenetic transaminase elevation may have CD. In fact, a wide spectrum of liver injuries in children and adults may be related to CD, particularly: a) mild parenchymal damage characterized by absence of any clinical signs or symptoms suggesting chronic liver disease, and by non-specific histological changes reversible on a gluten-free diet; b) chronic liver damage with autoimmune etiology, including autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis, which may be associated with CD but are generally unaffected by gluten withdrawal; and c) severe liver failure and decompensated cryptogenetic liver cirrhosis, potentially treatable with a gluten-free diet. Such different types of liver injuries may represent one same disorder where individual factors, such as genetic predisposition, precocity, and duration of exposure to gluten may influence reversibility of liver damage. A rigorous cross-checking for asymptomatic liver damage in CD individuals and, conversely, for CD in any cryptogenic liver disorder, including end-stage liver failure, is recommended. PMID:18271663

Cantarero Vallejo, M D; Gómez Camarero, J; Menchén, L; Pajares Díaz, J A; Lo Iacono, O

2007-11-01

309

Hepatitis C: Sex and Sexuality  

MedlinePLUS

... pass hepatitis C through other types of sexual contact, such as oral and anal sex? We do ... of spreading the hepatitis C virus through sexual contact? To reduce this chance, follow these guidelines: Have ...

310

Preventing hepatitis B or C  

MedlinePLUS

... You should take steps to prevent catching or spreading these viruses since these infections can cause chronic ... Screening of all donated blood has reduced the chance of getting hepatitis ... with hepatitis B infection should be reported to state ...

311

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 PMID:6433587

Riely, C. A.

1984-01-01

312

The effects of Insulin Pre-Administration in Mice Exposed to Ethanol: Alleviating Hepatic Oxidative Injury through Anti-Oxidative, Anti-Apoptotic Activities and Deteriorating Hepatic Steatosis through SRBEP-1c Activation  

PubMed Central

Alcoholic liver disease (ALD) has become an important liver disease hazard to public and personal health. Oxidative stress is believed to be responsible for the pathological changes in ALD. Previous studies have showed that insulin, a classic regulator of glucose metabolism, has significant anti-oxidative function and plays an important role in maintaining the redox balance. For addressing the effects and mechanisms of insulin pre-administration on ethanol-induced liver oxidative injury, we investigated histopathology, inflammatory factors, apoptosis, mitochondrial dysfunction, oxidative stress, antioxidant defense system, ethanol metabolic enzymes and lipid disorder in liver of ethanol-exposed mice pretreatment with insulin or not. There are several novel findings in our study. First, we found insulin pre-administration alleviated acute ethanol exposure-induced liver injury and inflammation reflected by the decrease of serum AST and ALT activities, the improvement of pathological alteration and the inhibition of TNF-? and IL-6 expressions. Second, insulin pre-administration could significantly reduce apoptosis and ameliorate mitochondrial dysfunction in liver of mice exposed to ethanol, supporting by decreasing caspases-3 activities and the ratio of Bax/Bcl-2, increasing mitochondrial viability and mitochondrial oxygen consumption, inhibition of the decline of ATP levels and mitochondrial ROS accumulation. Third, insulin pre-administration prevented ethanol-mediated oxidative stress and enhance antioxidant defense system, which is evaluated by the decline of MDA levels and the rise of GSH/GSSG, the up-regulations of antioxidant enzymes CAT, SOD, GR through Nrf-2 dependent pathway. Forth, the modification of ethanol metabolism pathway such as the inhibition of CYP2E1, the activation of ALDH might be involved in the anti-oxidative and protective effects exerted by insulin pre-administration against acute ethanol exposure in mice. Finally, insulin pre-administration deteriorated hepatic steatosis in mice exposed to ethanol might be through SRBEP-1c activation. In summary, these results indicated that insulin pre-administration effectively alleviated liver oxidative injury through anti-inflammatory, anti-oxidative and anti-apoptotic activities but also deteriorated hepatic steatosis through SRBEP-1c activation in mice exposed to ethanol. Our study provided novel insight about the effects and mechanisms of insulin on ethanol-induced liver injury.

Liu, Jiangzheng; Wang, Xin; Peng, Zhengwu; Zhang, Tao; Wu, Hao; Yu, Weihua; Kong, Deqing; Liu, Ying; Bai, Hua; Liu, Rui; Zhang, Xiaodi; Hai, Chunxu

2015-01-01

313

The problem of anicteric hepatitis  

Microsoft Academic Search

ORE THAN 43,000 cases of hepatitis were reported during the first 6 months of 1961. This incidence, the highest during the past decade, does not represent the true incidence of hepatitis, as neither anicteric nor serum-jaundice cases were included. The two forms of hepatitis differ in length of the incubation period, prodromal symptoms, source of entry of the virus, and

E. Clinton Texter; Higino C. Laureta

1965-01-01

314

Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol  

SciTech Connect

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{sup -}) 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{sup -} and hepatic ADH-normal (ADH{sup +}) 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 {approx} 1.5-fold greater in ADH{sup -} vs. ADH{sup +} 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{sup -} 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., E-mail: bkaphali@utmb.ed [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States); Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

2010-08-01

315

Fulminant viral hepatitis.  

PubMed

Acute liver failure (ALF) is a condition wherein the previously healthy liver rapidly deteriorates, resulting in jaundice, encephalopathy, and coagulopathy. There are approximately 2000 cases per year of ALF in the United States. Viral causes (fulminant viral hepatitis [FVH]) are the predominant cause of ALF in developing countries. Given the ease of spread of viral hepatitis and the high morbidity and mortality associated with ALF, a systematic approach to the diagnosis and treatment of FVH is required. In this review, the authors describe the viral causes of ALF and review the intensive care unit management of patients with FVH. PMID:23830658

Jayakumar, Saumya; Chowdhury, Raiyan; Ye, Carrie; Karvellas, Constantine J

2013-07-01

316

Gastric secretion and basal gastrin concentration in bilharzial hepatic fibrosis.  

PubMed Central

Gastric secretion and fasting plasma gastrin levels were investigated in 26 patients with bilharzial hepatic fibrosis and 26 controls. The groups did not differ in their basal secretion. When stimulated by intravenous infusion of histamine the maximal acid output in patients with bilharzial hepatic fibrosis was significantly less than in the control group. This was unlikely to be a result of neutralisation by reflux of alkaline duodenal contents as the volumes of reflux were not different from control subjects, but was compatible with a true reduction in gastric secretion as assessed by two-component hypothesis. Neither the lowered gastric acidity nor the liver damage in patients with bilharzial hepatic fibrosis correlated with circulating gastrin. The fasting levels of plasma gastrin in these patients were not different from controls. As in other liver diseases the cause of diminished gastric secretion remains unclear. PMID:30681

Boulos, P B; Okosdonossian, E T; Elmunshid, H A; Elmasri, S H; Hassan, M A; Hobsley, M

1978-01-01

317

Hepatic inflammation and fibrosis: Functional links and key pathways.  

PubMed

Inflammation is one of the most characteristic features of chronic liver disease of viral, alcoholic, fatty, and autoimmune origin. Inflammation is typically present in all disease stages and associated with the development of fibrosis, cirrhosis, and hepatocellular carcinoma. In the past decade, numerous studies have contributed to improved understanding of the links between hepatic inflammation and fibrosis. Here, we review mechanisms that link inflammation with the development of liver fibrosis, focusing on the role of inflammatory mediators in hepatic stellate cell (HSC) activation and HSC survival during fibrogenesis and fibrosis regression. We will summarize the contributions of different inflammatory cells, including hepatic macrophages, T and B lymphocytes, natural killer cells and platelets, as well as key effectors, such as cytokines, chemokines, and damage-associated molecular patterns. Furthermore, we will discuss the relevance of inflammatory signaling pathways for clinical liver disease and for the development of antifibrogenic strategies. (Hepatology 2015;61:1066-1079). PMID:25066777

Seki, Ekihiro; Schwabe, Robert F

2015-03-01

318

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. PMID:25067998

Maggiore, Giuseppe; Nastasio, Silvia; Sciveres, Marco

2014-01-01

319

Alpha-Lipoic Acid Protects against Hepatic Ischemia-Reperfusion Injury in Rats  

Microsoft Academic Search

Background and Aim: To evaluate the protective effect of alpha-lipoic acid in reducing oxidative damage after severe hepatic ischemia\\/reperfusion (IR) injury. Methods: Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by 60 min reperfusion period. Lipoic acid (100 mg\\/kg i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of

Ender Dulundu; Yahya Ozel; Umit Topalaoglu; Özer Sehirli; Feriha Ercan; Nursal Gedik

2007-01-01

320

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. PMID:23710219

Nakamura, Tadashi; Ohta, Yoshiji; Ohashi, Koji; Ikeno, Kumiko; Watanabe, Rie; Tokunaga, Kenji; Harada, Nobuhiro

2013-01-01

321

Protective Effect of Brazilian Propolis against Liver Damage with Cholestasis in Rats Treated with ?-Naphthylisothiocyanate.  

PubMed

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. PMID:23710219

Nakamura, Tadashi; Ohta, Yoshiji; Ohashi, Koji; Ikeno, Kumiko; Watanabe, Rie; Tokunaga, Kenji; Harada, Nobuhiro

2013-01-01

322

Cutaneous manifestations of viral hepatitis.  

PubMed

There are several extrahepatic cutaneous manifestations associated with hepatitis B and hepatitis C virus infection. Serum sickness and polyarteritis nodosa are predominantly associated with hepatitis B infection, whereas mixed cryoglobulinemia associated vasculitis and porphyria cutanea tarda are more frequently seen in hepatitis C infection. The clinico-pathogenic associations of these skin conditions are not completely defined but appear to involve activation of the host immune system including the complement system. Management of the aforementioned cutaneous manifestations of viral hepatitis is often similar to that done in cases without viral hepatitis, with control of immune activation being a key strategy. In cases associated with hepatitis B and C, control of viral replication with specific antiviral therapy is also important and associated with improvement in most of the associated clinical manifestations. PMID:25809574

Akhter, Ahmed; Said, Adnan

2015-02-01

323

The hepatitis B virus  

Microsoft Academic Search

DNA recombinant technology has radically changed hepatitis B virus (HBV) virology. The genetic organization, transcription and replication of the virus are basically understood, structures of integrated HBV sequences in hepatocellular carcinoma have been characterized, and new vaccines produced by recombinant DNA technique are being developed.

Pierre Tiollais; Christine Pourcel; Anne Dejean

1985-01-01

324

Hepatitis and African Americans  

MedlinePLUS

... but remains an area of concern for the African American population. In 2010, non-Hispanic Blacks were 1.5 times as likely to die ... Hispanic Whites. Among all ethnic groups in 2011, African Americans had the highest rate of Hepatitis B. African ...

325

Hepatic hemangioma: atypical appearance  

SciTech Connect

Recent reports indicate that computed tomography (CT) after bolus injection of contrast material is diagnostically specific for hemangioma, replacing the need for angiography in a high percentage of patients. The authors report a unique hepatic hemangioma that showed early diffuse intense opacification by angiography and contrast-enhanced CT.

Mikulis, D.J.; Costello, P.; Clouse, M.E.

1985-07-01

326

Hepatic hemangioma: atypical appearance  

Microsoft Academic Search

Recent reports indicate that computed tomography (CT) after bolus injection of contrast material is diagnostically specific for hemangioma, replacing the need for angiography in a high percentage of patients. The authors report a unique hepatic hemangioma that showed early diffuse intense opacification by angiography and contrast-enhanced CT.

David J. Mikulis; Philip Costello; Melvin E. Clouse

1985-01-01

327

Viral hepatitis B  

Microsoft Academic Search

More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for more than 100 000 cases of liver cancer per year, with similar numbers of digestive haemorrhage and ascites episodes. Major breakthroughs have been made in diagnosis and treatment, and advances in molecular biology mean that the replicative state of the virus

Ching Lung Lai; Vlad Ratziu; Man-Fung Yuen; Thierry Poynard

2003-01-01

328

NK cells in chronic hepatitis C and hepatitis B Fine Characterization of Intra-hepatic NK cells Expressing  

E-print Network

1 NK cells in chronic hepatitis C and hepatitis B Fine Characterization of Intra-hepatic NK cells Expressing Natural Killer Receptors in Chronic Hepatitis B and C Paula Bonorino1,2* , Muhammad Ramzan 1. The proportions of intra-hepatic NK cells expressing either NKG2A, and/or CD158a,h, CD158b,j differed

Boyer, Edmond

329

P. Roingeard -Journal of Viral Hepatitis 2013 ; 20, 77-84. Page 1 Hepatitis C virus diversity and hepatic steatosis  

E-print Network

P. Roingeard - Journal of Viral Hepatitis 2013 ; 20, 77-84. Page 1 REVIEW Hepatitis C virus diversity and hepatic steatosis P. Roingeard. INSERM U966, Université François Rabelais & CHRU de Tours, 10, published in "Journal of Viral Hepatitis 2013;20(2):77-84" #12;P. Roingeard - Journal of Viral Hepatitis

Paris-Sud XI, Université de

330

Extracellular adenosine controls NKT-cell-dependent hepatitis induction.  

PubMed

Extracellular adenosine regulates inflammatory responses via the A2A adenosine receptor (A2AR). A2AR deficiency results in much exaggerated acute hepatitis, indicating nonredundancy of adenosine-A2AR pathway in inhibiting immune activation. To identify a critical target of immunoregulatory effect of extracellular adenosine, we focused on NKT cells, which play an indispensable role in hepatitis. An A2AR agonist abolished NKT-cell-dependent induction of acute hepatitis by concanavalin A (Con A) or ?-galactosylceramide in mice, corresponding to downregulation of activation markers and cytokines in NKT cells and of NK-cell co-activation. These results show that A2AR signaling can downregulate NKT-cell activation and suppress NKT-cell-triggered inflammatory responses. Next, we hypothesized that NKT cells might be under physiological control of the adenosine-A2AR pathway. Indeed, both Con A and ?-galactosylceramide induced more severe hepatitis in A2AR-deficient mice than in WT controls. Transfer of A2AR-deficient NKT cells into A2AR-expressing recipients resulted in exaggeration of Con A-induced liver damage, suggesting that NKT-cell activation is controlled by endogenous adenosine via A2AR, and this physiological regulatory mechanism of NKT cells is critical in the control of tissue-damaging inflammation. The current study suggests the possibility to manipulate NKT-cell activity in inflammatory disorders through intervention to the adenosine-A2AR pathway. PMID:24448964

Subramanian, Meenakshi; Kini, Radhika; Madasu, Manasa; Ohta, Akiko; Nowak, Michael; Exley, Mark; Sitkovsky, Michail; Ohta, Akio

2014-04-01

331

Damage and fatigue Continuum damage mechanics modeling  

E-print Network

Damage and fatigue Continuum damage mechanics modeling for fatigue of materials and structures Cachan Cedex, France desmorat@lmt.ens-cachan.fr ABSTRACT. Application of damage mechanics to fatigue damage mechanics (CDM) is a powerful tool to model the degrada- tion of materials, the stress softening

332

VACCINE INFORMATION STATEMENT Hepatitis A Vaccine  

E-print Network

VACCINE INFORMATION STATEMENT Hepatitis A Vaccine What You Need to Know Many Vaccine Information://www.immunize.org/vis 1 What is hepatitis A? Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in the stool of people with hepatitis A. It is usually spread by close personal contact

Leistikow, Bruce N.

333

VACCINE INFORMATION STATEMENT Hepatitis B Vaccine  

E-print Network

VACCINE INFORMATION STATEMENT Hepatitis B Vaccine What You Need to Know Many Vaccine Information://www.immunize.org/vis What is hepatitis B? Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. · In 2009, about 38,000 people became infected with hepatitis B. · Each year about 2

Leistikow, Bruce N.

334

VACCINE INFORMATION STATEMENT Hepatitis B Vaccine  

E-print Network

VACCINE INFORMATION STATEMENT Hepatitis B Vaccine What You Need to Know Many.Visitehttp://www.immunize.org/vis 1 What is hepatitis B? Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. · In2009,about38,000peoplebecameinfectedwith hepatitis B. · Eachyearabout2,000to4

Tennessee, University of

335

Durchbruch bei der Therapie der Hepatitis C  

E-print Network

Durchbruch bei der Therapie der Hepatitis C: Segen für die Patienten ­ Albtraum für die Behandler -Virushepatitis Oktober 2012 #12;H. Wedemeyer -Virushepatitis Oktober 2012 Hepatitisviren Hepatitis A Feinstone 1973 RNA Hepatitis B Blumberg 1965 DNA Hepatitis C Houghton 1988 RNA Hepatitis D Rizzetto 1977 RNA

Manstein, Dietmar J.

336

Hepatitis B and human immunodeficiency virus co-infection  

PubMed Central

Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy. PMID:25516647

Phung, Bao-Chau; Sogni, Philippe; Launay, Odile

2014-01-01

337

Serum Fibronectin Levels in Acute and Chronic Viral Hepatitis Patients  

PubMed Central

Background: The aim of this study was to investigate the serum fibronectin (FN) levels and liver enzyme activities in patients with acute hepatitis (A, B, C) and chronic viral hepatitis (B, C); determine whether the virus types correlated with disease severity; and assess whether FN could be used as a marker of virus type or disease severity in patients. Methods: A total of 60 subjects were enrolled in the study, including 20 patients with acute hepatitis (A, B, C), 20 with chronic hepatitis (B, C), and 20 healthy controls. Serum fibronectin (FN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and albumin were measured in all patients from blood samples. Results: Serum FN levels were significantly lower in acute (122.9 ?g/mL (SD 43.1), P < 0.001) and chronic hepatitis patients (135.7 ?g/mL (SD 46.0), P < 0 .001) compared to controls 221.4 ?g/mL (SD 32.5). A negative correlation was found between serum FN and AST (r2 = 0.528, P < 0.001), ALT (r2 = 0.425, P < 0.001), and GGT (r2 = 0.339, P < 0.001). Additionally, high serum GGT levels (? = –0.375, P = 0.010), and low serum albumin levels (? = –0.305, P = 0.008) were associated with low serum FN levels. Conclusion: Serum FN levels were lower in both acute and chronic hepatitis patients, and an inverse relationship between serum FN and serum AST, ALT, and GGT levels was found. A decrease in serum FN levels may indicate hepatitis severity as AST and ALT represent hepatocyte damage. PMID:24639609

ERTURK, Ayse; CURE, Erkan; OZKURT, Zulal; PARLAK, Emine; CURE, Medine Cumhur

2014-01-01

338

Effect of graded hypoxia on the rat hepatic tissue oxygenation and energy metabolism monitored by near-infrared and 31P nuclear magnetic resonance spectroscopy  

Microsoft Academic Search

Alteration in hepatic cellular adenosine triphosphate (ATP) levels has been shown to be a sensitive index for hypoxic damage. Hepatic ATP metabolism can be monitored by 31P nuclear magnetic resonance (NMR). Near-infrared spectroscopy (NIRS) can measure tissue oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and cy- tochrome oxidase (Cyt Ox), which reflect ATP produc- tion. In this study, hepatic oxygenation parameters have been

ALEXANDER M. SEIFALIAN; EL-HAMID EL-DESOKY; DAVID T. DELPY; BRIAN R. DAVIDSON

2001-01-01

339

Caroli Disease, Caroli Syndrome, and Congenital Hepatic Fibrosis  

Microsoft Academic Search

\\u000a The cystic diseases of the liver are mostly autosomal recessive disorders with variable intrahepatic biliary dilatation and\\u000a increased hepatic fibrosis either as part of the underlying defect or as a result of liver damage from recurrent episodes\\u000a of ascending cholangitis. Caroli disease (CD) denotes congenital saccular intrahepatic dilatation of the biliary tree. Caroli\\u000a syndrome (CS) is a more common disorder

Ronen Arnon; Henrietta Kotlus Rosenberg; Frederick J. Suchy

340

Hepatitis E in India.  

PubMed

Institute of Pediatric Gastroenterology is superspecialised referral institute for all Pediatric Gastroenterological diseases from all over the country and for adjoining countries. We have our data and experience on 10,500 cases of proven Hepatitis E (HEV) in Pediatric population. HEV is non-enveloped 27-30 nm diameter RNA virus, prototype for alpha-like supergroup of positive stranded RNA virus. Indian HEV strain has 97% nucleotide and 98% amino acid sequence identity with Chinese strains but much diversity with Mexican strain. More than 70% acute hepatitis occurring in Pediatric population in this subcontinent are caused by HEV and 80% of these are sporadic. 90% cases were enterically transmitted, spread primarily by fecally contaminated drinking water (70%) and by food (20%), in 9.5% case spread probably was because of person to person and household contact. We could demonstrate HEV in urine, respiratory secretions. Interestingly we found HEV in insects like Flies, Cockroaches, and also in engorged Bedbugs and in Mosquitoes, apart from briefly boiled Mussels, and partially cooked cockles. Maternal-neonatal transmission could be seen if mother had HEV infection in third trimester of pregnancy. In 5 cases we could demonstrate HEV in breast milk. By studying on 10 volunteers, 40% have anicteric form only accompanied by anorexia, epigastric pain. HEV appeared in serum before the icteric phase. Shedding of virus in stool starts before the icteric phase and continued during the high levels of abnormal ALT. Hepatitis IgG anti-HEV persist up to 4 years. In 5 cases we could establish Transfusion associated Hepatitis (TAH). No chronicity could be documented. 5% cases had fulminant viral Hepatitis (FVH)/Sub fulminant viral Hepatitis (SVH), alpha-interferon (IFN) has been proved beneficial in these cases, further use of intravenous PGEl could also be beneficial. Inadequate chlorination of drinking water was an important additional factor for causing epidemics. A free residual chlorine concentration of at least 0.5 mg/l for minimum of 30 minutes is considered adequate as quality of drinking water. PMID:9684519

Tomar, B S

1998-01-01

341

Fulminant Hepatic Failure Secondary to Primary Hepatic Angiosarcoma  

PubMed Central

Background. Hepatic angiosarcoma is a rare and aggressive tumor that often presents at an advanced stage with nonspecific symptoms. Objective. To report a case of primary hepatic angiosarcoma in an otherwise healthy man with normal liver function tests two months prior to presenting with a short period of jaundice that progressed to fulminant hepatic failure. Methods. Case report and review of literature. Conclusion. This case illustrates the rapidity of progression to death after the onset of symptoms in a patient with hepatic angiosarcoma. Research on early diagnostic strategies and newer therapies are needed to improve prognosis in this rare and poorly understood malignancy with limited treatment options.

Abegunde, Ayokunle T.; Aisien, Efe; Mba, Benjamin; Chennuri, Rohini; Sekosan, Marin

2015-01-01

342

Hepatitis C: Information on Testing and Diagnosis  

MedlinePLUS

... the bloodstream when someone gets infected. Hepatitis C Antibody Test Results When getting tested for Hepatitis C, ... health clinics. Non-Reactive or Negative Hepatitis C Antibody Test • A non-reactive or negative antibody test ...

343

Testing for the Hepatitis C Virus  

MedlinePLUS

... Summary – Sept. 13, 2013 Testing for the Hepatitis C Virus Formats View PDF (PDF) 999 kB Download ... this summary. Understanding the Condition What is hepatitis C? Hepatitis C is a disease caused by a ...

344

Hepatitis A and the Vaccine during Pregnancy  

MedlinePLUS

... or visit us online at: www.OTISpregnancy.org . Hepatitis A and the Vaccine during Pregnancy In every ... and advice from your healthcare professional. What is Hepatitis A? Hepatitis A is a short-term viral ...

345

77 FR 45895 - World Hepatitis Day, 2012  

Federal Register 2010, 2011, 2012, 2013, 2014

...comprehensive viral hepatitis prevention and treatment services. On World Hepatitis Day, let us raise awareness of the global health threat of viral hepatitis, renew our support for those living with the disease, and recommit to a future free...

2012-08-02

346

Genetics Home Reference: Congenital hepatic fibrosis  

MedlinePLUS

... Research studies PubMed Recent literature Conditions > Congenital hepatic fibrosis On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed January 2012 What is congenital hepatic fibrosis? Congenital hepatic fibrosis is a disease of the ...

347

Damaged Skylab  

NASA Technical Reports Server (NTRS)

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop, that protected it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows the exterior skin of the workshop discolored by solar radiation. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

1973-01-01

348

Damaged Skylab  

NASA Technical Reports Server (NTRS)

The Saturn V vehicle, carrying the unmarned orbital workshop for the Skylab-1 mission, lifted off successfully and all systems performed normally. Sixty-three seconds into the flight, engineers in the operation support and control center saw an unexpected telemetry indication that signalled that damages occurred on one solar array and the micrometeoroid shield during the launch. The micrometeoroid shield, a thin protective cylinder surrounding the workshop protecting it from tiny space particles and the sun's scorching heat, ripped loose from its position around the workshop. This caused the loss of one solar wing and jammed the other. Still unoccupied, the Skylab was stricken with the loss of the heat shield and sunlight beat mercilessly on the lab's sensitive skin. Internal temperatures soared, rendering the station uninhabitable, threatening foods, medicines, films, and experiments. This image, taken during a fly-around inspection by the Skylab-2 crew, shows a crippled Skylab in orbit. The crew found their home in space to be in serious shape; the heat shield gone, one solar wing gone, and the other jammed. The Marshall Space Flight Center (MSFC) developed, tested, rehearsed, and approved three repair options. These options included a parasol sunshade and a twin-pole sunshade to restore the temperature inside the workshop, and a set of metal cutting tools to free the jammed solar panel.

1973-01-01

349

Minimal hepatic encephalopathy  

PubMed Central

Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of cirrhotic patients. By definition, it has no obvious clinical manifestation and is characterized by neurocognitive impairment in attention, vigilance and integrative function. Although often not considered to be clinically relevant and, therefore, not diagnosed or treated, MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis of MHE has traditionally been achieved through neuropsychological examination, psychometric tests or the newer critical flicker frequency test. A new smartphone application (EncephalApp Stroop Test) may serve to function as a screening tool for patients requiring further testing. In addition to physician reporting and driving restrictions, medical treatment for MHE includes non-absorbable disaccharides (eg, lactulose), probiotics or rifaximin. Liver transplantation may not result in reversal of the cognitive deficits associated with MHE. PMID:24106728

Stinton, Laura M; Jayakumar, Saumya

2013-01-01

350

Primary hepatic benign schwannoma  

PubMed Central

Schwannoma is predominantly a benign neoplasm of the Schwann cells in the neural sheath of the peripheral nerves. Occurrence of schwannoma in parenchymatous organs, such as liver, is extremely rare. A 64-year-old man without neurofibromatosis was observed to have a space-occupying lesion of 23mm diameter in the liver during follow-up examination for a previously resected gastrointestinal stromal tumor (GIST) in the small intestine. He underwent lateral segmentectomy of the liver under a provisional diagnosis of hepatic metastatic recurrence of the GIST. Histological examination confirmed the diagnosis of a benign schwannoma, confirmed by characteristic pathological findings and positive immunoreactions with the neurogenic marker S-100 protein, but negative for c-kit, or CD34. The tumor was the smallest among the reported cases. When the primary hepatic schwannoma is small in size, preoperative clinical diagnosis is difficult. Therefore, this disease should be listed as differential diagnosis for liver tumor with clinically benign characteristics. PMID:22530081

Hayashi, Michihiro; Takeshita, Atsushi; Yamamoto, Kazuhiro; Tanigawa, Nobuhiko

2012-01-01

351

Management of hepatic adenomatosis.  

PubMed

Hepatic adenomatosis (HeAs) is a rare clinical entity defined by the presence of 10 or more hepatic adenomas (HA) within the background of an otherwise normal liver parenchyma, in the absence of glycogen storage disease or anabolic steroid use. HA is a benign tumor associated with oral contraceptive use. Recent advances in pathogenesis and classification of HA have questioned the distinction between these two diseases. HA are currently classified into four different subtypes with genotypic and phenotypic correlation: HNF-1a inactivated HA, B-catenin activated HA, inflammatory HA, and undetermined subtype. The clinical presentation of HA depends on the lesion size and the subtype. MRI using hepatospecific contrast agents is helpful in diagnosing the most common subtypes. When diagnosis is uncertain, biopsy with immunohistochemistry is used to diagnose and classify the lesions. Management is governed by the molecular subtype and tumor size. Pregnancy is not routinely discouraged but management is individualized. PMID:25740249

Thapar, Manish; Grapp, Oleg; Fisher, Constantine

2015-03-01

352

Hepatitis E: current status.  

PubMed

Acute hepatitis E is a very common disease in developing countries, to the point that, according to World Health Organization estimates, one third of the world's population has been exposed to HEV. It also causes outbreaks in refugee camps or after natural disasters such as floods or earthquakes. Sporadic cases of acute hepatitis have been observed in practically all European countries and other developed geographical areas, not only in travelers from endemic countries but also in people with no risk factors. But, lately, new aspects of this infection are appearing in industrialized countries such as the possibility of the disease becoming chronic in transplant patients, the immunocompromised in general, and even in patients with previous liver disease who are immunocompetent. In this comprehensive review, we summarize the current knowledge on HEV infection. PMID:24038432

Pérez-Gracia, María Teresa; Mateos Lindemann, María Luísa; Caridad Montalvo Villalba, María

2013-11-01

353

What I Need to Know about Hepatitis A  

MedlinePLUS

... Liver Disease > Hepatitis A | Share External Link Disclaimer Liver Disease Hepatitis A Alternate Versions PDF Version (556 KB) Additional Links ? Hepatitis B Hepatitis C Viral Hepatitis: A through E Contact ...

354

Hepatitis C and Kidney Disease  

PubMed Central

Multiple extrahepatic manifestations have been associated with chronic hepatitis C, the most important among them being cryoglobulinemia, glomerulonephritis, porphyria cutanea tarda, lichen planus, seronegative arthritis, and lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001) and El-Serag et al. (2002). We will discuss in this paper chronic hepatitis C- related kidney disease and course and management of patients with chronic hepatitis C in special circumstances like hemodialysis and kidney transplantation. PMID:21188196

Hayat, Ashik; Mitwalli, Ahmad

2010-01-01

355

Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B  

PubMed Central

AIM: To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation. METHODS: DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced. RESULTS: HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right virus/host junction was situated at nucleotide 1 774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged. The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time. CONCLUSION: Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis. PMID:16425409

Kimbi, Gerald C; Kramvis, Anna; Kew, Michael C

2005-01-01

356

Serological diagnosis of acute viral hepatitis  

Microsoft Academic Search

Fifty cases of symptomatic acute viral hepatitis presenting at the Washington, D.C., Veterans Administration Medical Center between 1976 and 1977 were tested for serological markers of hepatitis virus infection. The etiology of the acute hepatitis appeared to be hepatitis A virus in 20%, hepatitis B virus in 52%, non-A, non-B agents in 22%, delta hepatitis in 4%, and infectious mononucleosis

Jay H. Hoofnagle; Antonio Ponzetto; Lars R. Mathiesen; Jeanne G. Waggoner; Z. Buskell Bales; Leonard B. Seeff

1985-01-01

357

Hepatitis E Virus Infection  

PubMed Central

SUMMARY Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

Dalton, Harry R.; Abravanel, Florence; Izopet, Jacques

2014-01-01

358

Clinical presentation of hepatitis E.  

PubMed

Hepatitis E is a form of acute hepatitis, which is caused by infection with hepatitis E virus. The infection is transmitted primarily through fecal-oral route and the disease is highly endemic in several developing countries with opportunities for contamination of drinking water. In these areas with high endemicity, it occurs as outbreaks and as sporadic cases of acute hepatitis. The illness often resembles that associated with other hepatotropic viruses and is usually self-limiting; in some cases, the disease progresses to acute liver failure. The infection is particularly severe in pregnant women. Patients with chronic liver disease and superimposed HEV infection can present with severe liver injury, the so-called acute-on-chronic liver failure. In recent years, occasional sporadic cases with locally acquired hepatitis E have been reported from several developed countries in Europe, United States, and Asia. In these areas, in addition to acute hepatitis similar to that seen in highly endemic areas, chronic hepatitis E has been reported among immunosuppressed persons, in particular solid organ transplant recipients. HEV-infected mothers can transmit the infection to foetus, leading to premature birth, increased fetal loss and hypoglycaemia, hypothermia, and anicteric or icteric acute hepatitis in the newborns. Occasional cases with atypical non-hepatic manifestations, such as acute pancreatitis, hematological abnormalities, autoimmune phenomena, and neurological syndromes have been reported from both hyperendemic and non-endemic regions. The pathogenesis of these manifestations remains unclear. PMID:21458513

Aggarwal, Rakesh

2011-10-01

359

Hepatitis - Multiple Languages: MedlinePlus  

MedlinePLUS

... ?????? ????? ???????? - ??????? Bilingual PDF Health Information Translations Chinese - Simplified (????) Viral Hepatitis ????? - ???? (Chinese - Simplified) Bilingual PDF Health Information Translations Chinese - Traditional (????) Viral Hepatitis ????? - ???? (Chinese - ...

360

Viral hepatitis in India.  

PubMed

Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a hepatitis registry and formulation of government-supported prevention and control strategies. PMID:17100109

Acharya, S K; Madan, Kaushal; Dattagupta, S; Panda, S K

2006-01-01

361

Radioembolization of hepatic tumors  

PubMed Central

Unresectable primary and metastatic liver tumors are a leading cause of cancer mortality and morbidity. This remains a challenging and key task for every oncologist despite significant advances that have been made with selective targeted systemic agents and in technology advances with radiotherapy delivery. Radioembolization (RE) is a technique of permanently implanting microspheres containing Yttrium-90 (90Y), a beta-emitting isotope with a treatment range of 2 mm, into hepatic tumors. This form of brachytherapy utilizes the unique dual vascular anatomy of the liver to preferentially deliver radioactive particles via the hepatic artery to tumor, sparing normal liver parenchyma. The main treatment inclusion criteria are patients with solid tumors, compensated liver functions, life expectancy of at least three months, and ECOG performance status 0-2. Benefit of RE has been proven in patients that have low-to-moderate extrahepatic disease burden, prior liver radiotherapy, heavy prior chemotherapy and biologic agent exposure, and history of hepatic surgery or ablation. Most of the clinical evidence is reported in metastatic colorectal, and neuroendocrine tumors (NET), and primary hepatocellular cancer. A growing body of data supports the use of RE in hepatic metastatic breast cancer, intrahepatic cholangiocarinoma, and many other metastatic tumor types. Side effects are typically mild constitutional and GI issues limited to the first 7-14 days post treatment, with only 6% grade 3 toxicity reported in large series. Potentially serious or fatal radiation induced liver disease is extremely rare, reported in only 1% or fewer in major series of both metastatic and primary tumors treated with RE. Currently, high priority prospective clinical trials are testing RE combined with chemotherapy in first line therapy for colorectal hepatic metastases, and combined with sorafenib for hepatocellular carcinomas (HCCs). Fortunately, this beneficial and now widely available therapy is being increasingly incorporated into the standard therapy algorithms of multidisciplinary GI cancer teams worldwide. This form of radiotherapy differs significantly from daily external beam radiotherapy in many ways, particularly in dose rate, dosimetric coverage and duration of radiation delivery, side effects, and patient selection factors. A wealth of experience using RE in solid tumors exists and ongoing major prospective clinical trials will soon clarify the role of RE in the management of metastatic colorectal liver metastases. PMID:24982766

2014-01-01

362

Immunology of hepatitis B virus and hepatitis C virus infection  

Microsoft Academic Search

More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and\\/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and

Michelina Nascimbeni; Barbara Rehermann

2005-01-01

363

Viral hepatitis: Treating hepatitis C in injection drug users.  

PubMed

A large proportion of hepatitis C in the developed world occurs in injection drug users. Treatment uptake in this population is low, despite the rising burden of HCV-related liver disease. Multiple barriers preclude the optimal care of hepatitis C in injection drug users, including low medication adherence and HCV re-infection. PMID:23999322

Soriano, Vincent; Gallego, Lucía

2013-10-01

364

Designing Immune Therapy for Chronic Hepatitis B  

PubMed Central

Presently-available antiviral drugs may not be a satisfactory option for treatment of patients with chronic hepatitis B (CHB). In spite of presence of several antiviral drugs, sustained off-treatment clinical responses are not common in CHB patients treated with antiviral drugs. In addition, antiviral drug treatment may have limited effects on blocking the progression of HBV-related complications. However, substantial long-term risk of viral resistance and drug toxicity are related with maintenance antiviral therapy in CHB patients with presently-available antiviral agents. The infinite treatments with antiviral drugs for CHB patients are also costly and may be unbearable by most patients of developing and resource-constrained countries. In this situation, there is pressing need to develop new and innovative therapeutic approaches for patients with chronic hepatitis B virus (HBV) infection. Immune therapy has emerged as an alternate therapeutic approach for CHB patients because studies have shown that host immunity is either impaired or derailed or distorted or diminished in CHB patients compared to patients with acute resolved hepatitis B who contain the HBV replication and control liver damages. Both non antigen-specific immune modulators and HBV antigen-specific agents have been used in CHB patients during last three decades. However, similar to antiviral therapy, the ongoing regimens of immune therapeutic approaches have also been unable to show real promises for treating CHB patients. The concept of immune therapy for treating CHB patients seems to be rationale and scientific, however, concerns remain about suitable designs of immune therapy for CHB patients. PMID:25755566

Fazle Akbar, Sheikh Mohammad; Al-Mahtab, Mamun; Hiasa, Yoichi

2014-01-01

365

Hepatitis C virus associated glomerulopathies  

PubMed Central

Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type?I?MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-? plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated. PMID:24976695

Ozkok, Abdullah; Yildiz, Alaattin

2014-01-01

366

Hepatitis C virus associated glomerulopathies.  

PubMed

Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-? plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated. PMID:24976695

Ozkok, Abdullah; Yildiz, Alaattin

2014-06-28

367

Hepatic Oxidative Stress, Genotoxicity and Vascular Dysfunction in Lean or Obese Zucker Rats  

PubMed Central

Metabolic syndrome is associated with increased risk of cardiovascular disease, which could be related to oxidative stress. Here, we investigated the associations between hepatic oxidative stress and vascular function in pressurized mesenteric arteries from lean and obese Zucker rats at 14, 24 and 37 weeks of age. Obese Zucker rats had more hepatic fat accumulation than their lean counterparts. Nevertheless, the obese rats had unaltered age-related level of hepatic oxidatively damaged DNA in terms of formamidopyrimidine DNA glycosylase (FPG) or human oxoguanine DNA glycosylase (hOGG1) sensitive sites as measured by the comet assay. There were decreasing levels of oxidatively damaged DNA with age in the liver of lean rats, which occurred concurrently with increased expression of Ogg1. The 37 week old lean rats also had higher expression level of Hmox1 and elevated levels of DNA strand breaks in the liver. Still, both strain of rats had increased protein level of HMOX-1 in the liver at 37 weeks. The external and lumen diameters of mesenteric arteries increased with age in obese Zucker rats with no change in media cross-sectional area, indicating outward re-modelling without hypertrophy of the vascular wall. There was increased maximal response to acetylcholine-mediated endothelium-dependent vasodilatation in both strains of rats. Collectively, the results indicate that obese Zucker rats only displayed a modest mesenteric vascular dysfunction, with no increase in hepatic oxidative stress-generated DNA damage despite substantial hepatic steatosis. PMID:25738756

Løhr, Mille; Folkmann, Janne K.; Sheykhzade, Majid; Jensen, Lars J.; Kermanizadeh, Ali; Loft, Steffen; Møller, Peter

2015-01-01

368

Diabetes and Hepatitis B Vaccination  

MedlinePLUS

... is the recommendation for vaccinating children living with diabetes? In the United States, the hepatitis B vaccine is now part of the routine childhood vaccination schedule. In 1991, CDC and the ACIP recommended that all children and adolescents be vaccinated for hepatitis B. Estimates of vaccine ...

369

Hepatitis B virus and hepatocellular carcinoma  

PubMed Central

Chronic hepatitis B virus (HBV) infection is a major global cause of hepatocellular carcinoma (HCC). Individuals who are chronic carriers have a greater than 100-fold increased relative risk of developing the tumour. Several mechanisms of HBV-induced HCC have been proposed. Integration of HBV DNA into the genome of hepatocytes occurs commonly, although integration at cellular sites that are important for regulation of hepatocyte proliferation appears to be a rare event. Functions of the HBx protein are also potentially oncogenic. These include transcriptional activation of cellular growth regulatory genes, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA. The effects of HBx are mediated by interaction with cellular proteins and activation of cell signalling pathways. Variations in HBV genome sequences may be important in hepatocarcinogenesis, although their significance has not yet been completely elucidated. Necroinflammatory hepatic disease, which often accompanies chronic HBV infection, may contribute indirectly to hepatocyte transformation in a number of ways, including by facilitating HBV DNA integration, predisposing to the acquisition of cellular mutations and generating mutagenic oxygen reactive species. Although HCC is a malignancy with a poor prognosis, the availability of an effective vaccine against HBV infection, and its inclusion in the Expanded Programme of Immunization of many countries, augurs well for the eventual elimination of HBV-associated HCC. PMID:11454100

Arbuthnot, Patrick; Kew, Michael

2001-01-01

370

Hepatitis B Vaccines  

Microsoft Academic Search

\\u000a Key Principles\\u000a \\u000a Initial immunization strategies against hepatitis B virus (HBV) infection concentrated on high-risk groups. This strategy,\\u000a which was successful in individual situations, failed to reduce the incidence and prevalence of HBV in the general population.\\u000a \\u000a \\u000a \\u000a As a result, in 1991 the World Health Organization (WHO) has recommended that HBV universal immunization should be integrated\\u000a into national immunization programs in

Oren Shibolet; Daniel Shouval

371

Hepatic alveolar echinococcosis.  

PubMed

 Alveolar hydatid disease is a highly malignant form of echinococcosis caused by the larvae of the cestode echinococcus multilocularis. Alveolar hydatid disease always affects the liver and can metastasise to the lung and brain. Early diagnosis and precise evaluation of the localization as well as the extent of lesions are essential for treatment. In this report, we present ultrasound and computed tomography findings in a patient with hepatic alveolar echinococcosis. The patient, who was presented with hepatomegaly, jaundice, and an infiltrative solid tumor, diagnosed by ultrasound and computed tomography. In contrast to hydatid cyst caused by echinococcus granulosus, this is a rare disease in Iran. PMID:25773697

Farrokh, Donya; Zandi, Behrouz; Pezeshki Rad, Masoud; Tavakoli, Maryam

2015-03-01

372

[Imaging of hepatic angiosarcoma.  

PubMed

Primary hepatic angiosarcoma (PHA) is a very rare malignant tumour with imaging characteristics that can mimic atypical haemangioma (HA). This is a case report of a 47-year-old male with PHA. Contrast-enhanced ultrasound (CEUS) has shown to be effective in differentiating PHA from HA, CT has more variable findings, in MRI PHA can mimic HA, arteriovenous malformations and cystic metastases, and PET/CT can be used to verify the diagnosis. In this case CEUS was supplied with a contrast CT, MRI and PET/CT. An elevated fluorodeoxyglucose uptake within the left liver lobe was shown on PET/CT. PMID:25293570

Raunkilde, Louise; Brodersen, Louise Aarup; Rafaelsen, Søren Rafael

2014-08-18

373

Accelerated hepatic fibrosis in patients with combined hereditary hemochromatosis and chronic hepatitis C infection  

Microsoft Academic Search

Background\\/Aims: Hereditary hemochromatosis (HH) and chronic hepatitis C virus (HCV) infection can both result in hepatic fibrosis and cirrhosis. It has been proposed that iron overload and HCV may have potentiating effects on hepatic fibrogenesis. This study determined if HH patients with HCV would present with hepatic fibrosis\\/cirrhosis at a younger age and at a lower hepatic iron concentration compared

Hari H Diwakaran; Alex S Befeler; Robert S Britton; Elizabeth M Brunt; Bruce R Bacon

2002-01-01

374

Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model  

PubMed Central

Background/Aims The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. Methods The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. Results All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. Conclusions SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats. PMID:24516701

Lim, Ji Hwan; Kim, Joo-Hyun; Lee, Byoung Hwan; Seo, Pyoung Ju; Kang, Jung Mook; Jo, So Young; Park, Ji Hyun; Nam, Ryoung Hee; Chang, Hyun; Kwon, Jin-Won; Lee, Dong Ho

2014-01-01

375

Methamphetamine causes acute hyperthermia-dependent liver damage.  

PubMed

Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

2013-10-01

376

'Liver let die': oxidative DNA damage and hepatotropic viruses.  

PubMed

Chronic infections by the hepatotropic viruses hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for the development of hepatocellular carcinoma (HCC). It is estimated that more than 700,000 individuals per year die from HCC, and around 80?% of HCC is attributable to HBV or HCV infection. Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely elusive. Oxidative stress, in particular DNA lesions associated with oxidative damage, play a major contributory role in carcinogenesis, and are strongly linked to the development of many cancers, including HCC. A large body of evidence demonstrates that both HBV and HCV induce hepatic oxidative stress, with increased oxidative DNA damage being observed both in infected individuals and in murine models of infection. Here, we review the impact of HBV and HCV on the incidence and repair of oxidative DNA damage. We begin by giving a brief overview of oxidative stress and the repair of DNA lesions induced by oxidative stress. We then review in detail the evidence surrounding the mechanisms by which both viruses stimulate oxidative stress, before focusing on how the viral proteins themselves may perturb the cellular response to oxidative DNA damage, impacting upon genome stability and thus hepatocarcinogenesis. PMID:24496828

Higgs, Martin R; Chouteau, Philippe; Lerat, Hervé

2014-05-01

377

RELATED ARTICLES Pricey Hepatitis C Drug Draws  

E-print Network

Listen Tweet 28 RELATED ARTICLES Pricey Hepatitis C Drug Draws Criticism World Hepatitis Day Highlights Global Scourge, Hopes for Treatment News / Health Elimination of Chronic Hepatitis Feasible FILE A nurse vaccinates a child against hepatitis to prevent disease in Constitucion, Chile. Lisa Schlein July

Bogyo, Matthew

378

Inactive hepatic lipase in rat plasma  

Microsoft Academic Search

Hepatic lipase activity is detectable in liver but also in adrenal glands, ovaries, and plasma. The subunit size of hepatic lipase in liver, adrenal glands, and nonheparin plasma was compared. Hepatic lipase in liver and adrenal glands appeared as a 55 kDa band. In liver, a faint band of lower size was also detected. In nonheparin plasma, hepatic lipase appeared

Xavier Galan; Julia Peinado-Onsurbe; Josep Julve; David Ricart-Jané; Monique Q. Robert; Miquel Llobera; Ignasi Ramírez

2003-01-01

379

Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.  

PubMed

Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. PMID:23855291

Zakhari, Samir

2013-08-01

380

Primer for Teachers: Quick and Easy Liver Wellness, Hepatitis B and Substance Abuse Prevention Messages.  

ERIC Educational Resources Information Center

This guide provides information for teachers to use in teaching about liver wellness, hepatitis B, and substance abuse. The guide includes effective motivational techniques to help students understand how valuable their liver is to their health and well being. It also provides basic information to help students avoid liver damaging behaviors, such…

Thiel, Thelma King

381

Serological and histological follow up of chronic hepatitis B infection.  

PubMed Central

In order to study the clinical, serological, and morphological evolution of chronic hepatitis B virus infection in childhood, a prospective study has been carried out. A total of 90 children with a chronic infection were followed up for a mean (SD) of 3 (1.8) years. At the beginning of the study, 61 children were asymptomatic and 77 were household contacts of chronic carriers. Serologically 77 were hepatitis B e antigen (HBeAg) positive and 71 of them were positive to hepatitis B virus DNA. The mean alanine aminotransferase activities were higher among HBeAg positive patients than in antihepatitis B e (anti-HBe) positive ones. The most severe histological damage was also found among HBeAg positive patients. The annual seroconversion rate was 14%. A significant increase in the alanine aminotransferase activity was observed 13 (5.6) months before appearance of anti-HBe in the 85% of cases. Among anti-HBe positive patients, the alanine aminotransferase activities were normal in all except three (19%), two of whom had intrahepatic delta antigen. An increase in the histological activity was observed among patients who maintained HBeAg presence while an amelioration of liver damage was observed in anti-HBe carriers. PMID:2782931

Ruiz-Moreno, M; Camps, T; Aguado, J G; Porres, J C; Oliva, H; Bartolomé, J; Carreño, V

1989-01-01

382

Genetic similarity of hepatitis C virus and fibrosis progression in chronic and recurrent infection after liver transplantation  

Microsoft Academic Search

SUMMARY. The effect of hepatitis C virus (HCV) genetic heterogeneity on clinical features of post-transplantation hepatitis C is controversial. Different regions of the HCV genome have been associated with apoptosis, fibrosis, and other pathways leading to liver damage in chronic HCV infection. Besides, differences in immunodominant regions, such as NS3, may influence HCV-specific immune re- sponses and disease outcome. In

F.-X. Lopez-Labrador; M. A. Bracho; M. Berenguer; M. Coscolla; J. M. Rayon; M. Prieto; D. Carrasco; M. D. Gomez; A. Moya; F. Gonzalez-Candelas

2006-01-01

383

Role of ischemic preconditioning in hepatic ischemia-reperfusion injury  

PubMed Central

Background Investigation into less traumatic method of vascular occlusion during liver resection is the actual problem in hepatic surgery because of high level of complications such as liver failure. In this connection, the goal of our study was to determine the optimal model of vascular clamping. The research showed that vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique. Methods Forty white giant rabbits were divided randomly into four groups (n=10 in each group). In group I we used continuous Pringle maneuver by 30 min. In group II we used intermittent Pringle maneuver: 15 min of clamping/5 min of unclamping (reperfusion)/15 min of clamping. In group III we used intermittent Pringle maneuver with ischemic precondition: 5 min of ischemia/5 min of reperfusion, 10 min of ischemia/5 min of reperfusion/15 min of ischemia. Group IV (control group) is without hepatic ischemia. All animals were performed a liver biopsy at the end of the surgery. Five rabbits from each group underwent re-laparotomy on day 3 after surgery with biopsy samples being taken for studying reparative processes in liver parenchyma. Results Results of morphometric analysis were the best to illustrate different level of liver injury in the groups. Thus, there were 95.5% damaged hepatocytes after vascular occlusion in hepatic preparations in group I, 70.3% damaged hepatocytes in group II, and 42.3% damaged hepatocytes in group III. There were 5.3% damaged hepatocytes in the control group. Conclusions Vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique that does not involve major structural injuries and functional disorders in the remnant liver. Thus, it is amenable to translation into clinical practice and may improve outcomes in liver resection with inflow vascular occlusion. PMID:25202694

Boyko, Valeriy V.; Tyshchenko, Oleksandr M.; Skoryi, Denys I.; Kozlova, Tatiana V.; Gorgol, Natalia I.; Volchenko, Igor V.

2014-01-01

384

Hepatitis D and hepatocellular carcinoma  

PubMed Central

Hepatitis D virus (HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins, small and large hepatitis D antigens, surrounded by hepatitis B surface antigen. Superinfection with HDV in chronic hepatitis B is associated with a more threatening form of liver disease leading to rapid progression to cirrhosis. In spite of some controversy in the epidemiological studies, HDV infection does increase the risk of hepatocellular carcinoma (HCC) compared to hepatitis B virus (HBV) monoinfection. Hepatic decompensation, rather than development of HCC, is the first usual clinical endpoint during the course of HDV infection. Oxidative stress as a result of severe necroinflammation may progress to HCC. The large hepatitis D antigen is a regulator of various cellular functions and an activator of signal transducer and activator of transcription (STAT)3 and the nuclear factor kappa B pathway. Another proposed epigenetic mechanism by which HCC may form is the aberrant silencing of tumor suppressor genes by DNA Methyltransferases. HDV antigens have also been associated with increased histone H3 acetylation of the clusterin promoter. This enhances the expression of clusterin in infected cells, increasing cell survival potential. Any contribution of HBV DNA integration with chromosomes of infected hepatocytes is not clear at this stage. The targeted inhibition of STAT3 and cyclophilin, and augmentation of peroxisome proliferator-activated receptor ? have a potential therapeutic role in HCC.

Abbas, Zaigham; Abbas, Minaam; Abbas, Sarim; Shazi, Lubna

2015-01-01

385

Occult hepatitis B virus infection in hemodialysis patients in Japan.  

PubMed

Hepatitis B surface antigen is widely used in hepatitis B virus surveillance; patients who test negative for the antigen are judged to be uninfected. However, occult hepatitis B virus infection has been confirmed with hepatitis B virus DNA at low levels in the liver and peripheral blood in patients positive for hepatitis B core antibody or hepatitis B surface antibody, even if they test negative for hepatitis B surface antigen. To investigate the prevalence of occult hepatitis B virus in hemodialysis patients, we performed cross-sectional analysis of 161 hemodialysis patients in two related institutions for hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody. Hepatitis B surface antigen, hepatitis B core antibody, or hepatitis B surface antibody was present in 45 patients (28.0%). Hepatitis B virus DNA was present in six patients (3.7%), all of whom also tested positive for hepatitis B core antibody. Hepatitis B surface antibody positivity was unrelated in only one of the six patients. Four of the six patients were positive for hepatitis B surface antigen; however, two (1.3%) of these with occult hepatitis B virus infection were found to be hepatitis B surface antigen negative. Occult hepatitis B virus infection may be missed in hepatitis B virus surveillance using hepatitis B surface antigen alone; therefore, routine hepatitis B core antibody screening is necessary. Patients who test positive for hepatitis B core antibody should undergo further hepatitis B virus DNA testing to enable accurate hepatitis B virus screening. PMID:25363685

Saijo, Tomokatsu; Joki, Nobuhiko; Inishi, Yoji; Muto, Mikako; Saijo, Motohiko; Hase, Hiroki

2015-04-01

386

Lamivudine for chronic delta hepatitis.  

PubMed

Chronic delta hepatitis is a severe form of chronic liver disease caused by hepatitis delta virus (HDV) infection superimposed on chronic hepatitis B or the hepatitis B surface antigen (HBsAg) carrier state. Therapy of delta hepatitis is currently unsatisfactory. We have evaluated lamivudine (3-thiacytidine), an oral nucleoside analogue with marked effects against hepatitis B, as therapy in 5 patients with chronic hepatitis D. Five men, ages 38 to 65 years, were treated. All had HBsAg, antibody to HDV, and HDV RNA in serum, as well as persistent elevations in alanine aminotransferase (ALT) levels and liver histology showing severe chronic hepatitis with fibrosis or cirrhosis. Lamivudine was given in a dose of 100 mg orally daily for 12 months. Patients were monitored carefully and tested for HBsAg, HBV-DNA and HDV-RNA levels serially during the year of treatment and for 6 months thereafter. Liver biopsies were performed before therapy and repeated after 1 year. Serum levels of HBV DNA fell rapidly in all 5 patients, becoming undetectable even by polymerase chain reaction (PCR) in 4. However, all 5 patients remained HBsAg- and HDV-RNA-positive, and serum ALT levels and liver histology did not improve. All patients tolerated therapy well. When lamivudine was stopped, HBV-DNA levels returned to pretreatment values without a change in disease activity. Lamivudine is a potent inhibitor of HBV-DNA replication, but does not improve disease activity or lower HDV-RNA levels in patients with chronic delta hepatitis. PMID:10421666

Lau, D T; Doo, E; Park, Y; Kleiner, D E; Schmid, P; Kuhns, M C; Hoofnagle, J H

1999-08-01

387

Autochthonous hepatitis E in Southwest England: a comparison with hepatitis A  

Microsoft Academic Search

The incidence of hepatitis A is falling. In contrast, autochthonous hepatitis E is an emerging infection in developed countries.\\u000a The objective of this study was to compare both laboratory-confirmed cases of hepatitis A and autochthonous hepatitis E over\\u000a a 2-year period in Cornwall and Devon and anti-hepatitis A virus (HAV) IgG and anti-hepatitis E virus (HEV) IgG seroprevalence\\u000a in blood

H. R. Dalton; W. Stableforth; S. Hazeldine; P. Thurairajah; R. Ramnarace; U. Warshow; S. Ijaz; V. Ellis; R. Bendall

2008-01-01

388

The hepatic-arterial/portal-venous scintiangiogram in alcoholic hepatitis  

SciTech Connect

This study was designed to identify abnormalities in the hepatic-arterial/portal-venous scintiangiogram (SA) in alcoholic hepatitis (AH). SA's were performed in 35 patients with acute alcoholic hepatitis (AAH), 8; acute alcoholic hepatitis superimposed on cirrhosis (A/C), 14; and cirrhosis (C), 13. Posterior flows were done with a bolus of 10 mCi Tc-99m sulfur colloid with computer time-activity curves over the liver and left kidney. Curves were analyzed for per cent of hepatic arterial (HA) and portal venous contribution using the slope ratio method. Hepatic arterialization was estimated from the angle of the HA component of the curve. Reversal of the relative contribution of the hepatic and portal components of total flow were seen in all groups. Although quite severe in AH, the degree of reversal could not be used to differentiate among the groups. The average HA angle in AAH was 48.3 +- 8.1, in A/C 41.5 +- 10.6, and in C 30.4 +- 12.1. In reviewing the data of only those in the acute clinical phase of AH and not the recovery phase (1 AAH, 3 A/C) and those without other causes of alteration in hepatic arterialization (1 hepatoma, 1 portalcaval shunt, 6 renal failure), the average HA angle in AAH was 50.1 +- 6.6, 45.4 +- 8.2 in A/C, and 23.2 +- 4.2 in C. In 6 with renal failure (2 C, 2AAH, 2 A/C) the HA angle ws 52.7 +- 5.7. In all cases cirrhosis could be differentiated from both A/C (P=.05) and AAH (P<.01) using the HA angle. In absence of renal failure, portal shunt, or hepatoma, P was <.01 in both comparisons.

Stewart, C.; Sakimura, I.; Siegel, M.E.; Harley, H.; Lee, K.

1984-01-01

389

Hepatic lymphoid aggregates in chronic hepatitis C and mixed cryoglobulinemia  

Microsoft Academic Search

Summary  We have examined the clinical (virological and immunological), histological and immunohistochemical features of liver lymphoid nodules in hepatitis C virus-positive (HCV+)\\/mixed cryoglobulinemia (type II and III) and chronic hepatitis C. The clinical features of liver disease were found to be similar in all patients. In all these groups, liver lymphoid nodules were observed to a similar extent, being more frequent

Angelo Monteverde; Marco Ballarè; Stefano Pileri

1997-01-01

390

Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy  

PubMed Central

Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease. PMID:23921686

Rivera-Espinosa, Liliana; Floriano-Sánchez, Esaú; Pedraza-Chaverrí, José; Coballase-Urrutia, Elvia; Sampieri, Aristides; Ortega-Cuellar, Daniel; Cárdenas-Rodríguez, Noemí; Carmona-Aparicio, Liliana

2013-01-01

391

Modelling the epidemiology of hepatitis B in New Zealand.  

PubMed

Hepatitis B is a vaccine preventable disease caused by the hepatitis B virus (HBV) that can induce potentially fatal liver damage. It has the second highest mortality rate of all vaccine preventable diseases in New Zealand. Vaccination against HBV was introduced in New Zealand in 1988, and the country is now categorised with overall low endemicity but with areas of both high and medium endemic levels. We present an SECIR compartmental mathematical model, with the population divided into age classes, for the transmission of HBV using local data on incidence of infection and vaccination coverage. We estimate the basic reproduction number, R(0), to be 1.53, and show that the vaccination campaign has substantially reduced this below one. However, a large number of carriers remain in the population acting as a source of infection. PMID:21040731

Mann, Joanne; Roberts, Mick

2011-01-21

392

Prevalence of hepatitis B virus in chronic hepatitis B patients.  

PubMed

The aim of the current study was to detect HBV by Real time - PCR in chronic hepatitis B patients. Fifty-eight sera of chronic hepatitis B patients were subjected during the period March 2009 to April 2010 in Ilam cities in West of Iran. Sera assayed by real-time PCR and ELISA methods. Twenty serum samples from healthy volunteers and non-hepatitis B patients and negative for hepatitis B seromarkers served as negative controls for the study. Among fifty-eight sera, ELISA showed fifty-five (94.8%) of the samples were positive for HBsAg and three (5.2%) negative results obtained while real-time PCR specified fifty-eight (100%) positive results in chronic hepatitis B patients. HBsAg status did not necessarily reflect HBV DNA level in the serum, as 5.2% of chronic Hepatitis B patients were positive for HBV DNA but negative for HBsAg. HBV DNA was not found to be positive amongst any of the negative controls. Real time - PCR is a sensitive and reproducible assay for HBV DNA quantization. PMID:22838221

Sadeghifard, Nourkhoda; Mohebi, Reza; Sekawi, Zamberi; Ghafourian, Sobhan; Kazemian, Hossien; Rezaee, Mitra

2012-01-01

393

[Prevention of hepatic encephalopathy].  

PubMed

Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis. PMID:24480288

Morillas, Rosa M; Sala, Marga; Planas, Ramon

2014-06-01

394

Hepatitis C: extrahepatic manifestations.  

PubMed

Chronic hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations (EHM) affecting various organs in the body. Approximately 40% to 75% of patients with chronic HCV infection experience at least one clinical EHM during the course of the HCV infection. Mixed cryoglobulinemia (type 2) is the most documented EHM associated with chronic HCV infection. This has been documented in up to 50% of patients. Clinically, it presents as arthralgia, weakness, and cutaneous symptoms. Morphologically, immune complex depositions are identified in small vessels and glomerular capillary walls, leading to leukocytoclastic vasculitis in the skin and membranoproliferative glomerulonephritis in the kidney. In other EHMs of chronic HCV infection not related to cryoglobulinemia, such as Sjögren syndrome, lichen planus, and autoimmune thyroiditis, autoimmune processes resulting in chronic inflammatory infiltrates are thought to be the underlying mechanism. PMID:25478648

Metts, Julius; Carmichael, Lesley; Kokor, Winfred; Scharffenberg, Robert

2014-12-01

395

Toxic Hepatitis from Dimethylacetamide.  

PubMed

Two cases of toxic hepatitis from dimethylacetamide (DMAC) occurred among 25 employees on a new acrylic-fiber production line at a western U.S. manufacturing plant. Interesting features of these cases include: 1) inadequate personal protective equipment (PPE) for dermal exposures, resulting in skin penetration during maintenance and repair procedures; 2) the subjects of these case reports are female; all workers at the manufacturer's European plant were male, and DMAC-related liver dysfunction had not been encountered at that site; 3) the new American production line required more frequent maintenance and repair work than existing production lines at the European parent company, resulting in greater opportunities for DMAC exposure. Hepatotoxicity due to dermal absorption of DMAC and other amide-type solvents deserves special consideration in industrial settings. PMID:9891094

Baum; Suruda

1997-01-01

396

Herb medicine Yin-Chen-Hao-Tang ameliorates hepatic fibrosis in bile duct ligation rats.  

PubMed

The accumulation of hydrophilic bile acids in the liver is considered to play a pivotal role in the induction of hepatic injury. Yin-Chen-Hao-Tang (YCHT) decoction is an aqueous extract from three different herbs: Artemisia capillaries Thunb (Compositae), Gardenia jasminoides Ellis (Rubiaceae), Rheum officinale Baill (Polygonaceae), which has been recognized as a hepatoprotective agent for various types of liver diseases. Therefore, we used an experimental of biliary atresia model to test that YCHT plays a regulatory role in the pathogenesis of hepatic fibrosis. Hepatic damage with fibrosis was produced by common bile duct ligation (BDL) for 27 days in experimental cholestasis animal model. After surgery, YCHT (250 and 500mg/kg BW) oral administration once a day continued for 27 days. BDL caused a prominent liver collagen deposition that was supported by the increased alpha-SMA protein and mRNA expression of procollagen I. YCHT significantly decreased hepatic alpha-SMA protein levels and decreased in hydroxyproline and thiobarbituric acid reactive substances (TBARS) levels of BDL rats. On the other hand, the normalizing effect of YCHT (250mg/kg) on the TGF-beta1mRNA expression was independent on the dose of YCHT, 500mg/kg was not effectively changed the quantitative composition of mRNA levels. The study shows that hepatic hydroxyproline accumulation caused by hydrophilic bile acids accompanied by elevated hepatic lipid peroxidation, and hepatic collagen levels can be decreased in the presence of YCHT. In conclusion, long-term administration of YCHT in rats ameliorated the hydropholic bile acids induced hepatic injury that probably related to a reduced oxidant stress and degree of hepatic fibrosis. PMID:16989967

Lee, Tzung-Yan; Chang, Hen-Hong; Chen, Jenn-Han; Hsueh, Ming-Lung; Kuo, Jong-Jen

2007-01-19

397

Clevudine for hepatitis B.  

PubMed

Clevudine is distinguished from other oral agents by its sustained suppression of HBV DNA for several months after cessation of therapy, according to a comprehensive review of hepatitis B in the 2 October 2008 issue of the New England Journal of Medicine. Clevudine is differentiated by i) an unusual activation pathway to the biochemically active triphosphate; ii) a mechanism of action of clevudine triphosphate that inhibits multiple steps of the hepatitis B virus (HBV) intracellular life cycle; iii) a long half-life and iv) significant reduction of covalently closed circular DNA (cccDNA) in animal models. Clevudine was approved and is marketed in South Korea based on two 24-week phase III trials vs. placebo. In these studies with treatment-naïve patients, 59% of 248 HBeAg-positive patients had undetectable HBV DNA after 24 weeks of treatment compared with 92% of 89 HBeAg-negative patients, while the percentage of patients with normal liver enzymes was 68% in the HBeAg-positive patients and 75% in the HBeAg-negative patients (all statistically significant versus placebo). Follow-up studies include trials vs. lamivudine as well as a phase IV study of long-term clevudine. Larger and longer phase III trials in the United States, European Union, Asia and South America of clevudine vs. adefovir are ongoing. An ANRS-sponsored trial of clevudine vs. tenofovir vs. the combination of the two agents is poised to begin. Literature published through November 2008 and presentations from the 59th annual meeting of the American Association for the Study of Liver Diseases held 31 October to 4 November 2008 are included. PMID:19584963

Anderson, David Leif

2009-05-01

398

Microwave Ablation of Hepatic Malignancy  

PubMed Central

Microwave ablation is an extremely promising heat-based thermal ablation modality that has particular applicability in treating hepatic malignancies. Microwaves can generate very high temperatures in very short time periods, potentially leading to improved treatment efficiency and larger ablation zones. As the available technology continues to improve, microwave ablation is emerging as a valuable alternative to radiofrequency ablation in the treatment of hepatic malignancies. This article reviews the current state of microwave ablation including technical and clinical considerations. PMID:24436518

Lubner, Meghan G.; Brace, Christopher L.; Ziemlewicz, Tim J.; Hinshaw, J. Louis; Lee, Fred T.

2013-01-01

399

[Acute viral hepatitis during pregnancy].  

PubMed

Acute hepatitis has a very low incidence disease during pregnancy. However, it may be an important cause of jaundice during gestation which in cases of viral etiology can have a very high morbidity and mortality risk to the mother and the fetus. The purpose of this review is to update the available knowledge regarding viral hepatitis during pregnancy including description of the main etiologies, transmission route, maternal-fetal risk and possible management. PMID:21279287

Valdés R, Enrique; Sepúlveda M, Alvaro; Candia P, Paula; Lattes A, Karina

2010-12-01

400

Hepatic Manifestations in Hematological Disorders  

PubMed Central

Liver involvement is often observed in several hematological disorders, resulting in abnormal liver function tests, abnormalities in liver imaging studies, or clinical symptoms presenting with hepatic manifestations. In hemolytic anemia, jaundice and hepatosplenomegaly are often seen mimicking liver diseases. In hematologic malignancies, malignant cells often infiltrate the liver and may demonstrate abnormal liver function test results accompanied by hepatosplenomegaly or formation of multiple nodules in the liver and/or spleen. These cases may further evolve into fulminant hepatic failure. PMID:23606974

Murakami, Jun

2013-01-01

401

Hepatitis B prevention, diagnosis, treatment and care: a review.  

PubMed

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B (CHB) infection is associated with an increased risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). The likelihood of developing CHB is related to the age at which infection is acquired; the risk being lowest in adults and >90% in neonates whose mothers are hepatitis B e antigen positive. Treatment of CHB infection aims to clear HBV DNA and prevent the development of complications. There are currently seven drugs available for the treatment of CHB: five nucleos(t)ide analogues and two interferon-based therapies. Long-term treatment is often required, and the decision to treat is based on clinical assessment including the phase of CHB infection and the presence and extent of liver damage. A safe and effective HBV vaccine has been available since the early 1980s. Vaccination plays a central role in HBV prevention strategies worldwide, and a decline in the incidence and prevalence of HBV infection following the introduction of universal HBV vaccination programmes has been observed in many countries including the USA and parts of South East Asia and Europe. Post-exposure prophylaxis (PEP) with HBV vaccine +/- hepatitis B immunoglobulin is highly effective in preventing mother to child transmission and in preventing transmission following sharps injuries, sexual contact and other exposures to infected blood and body fluids. Transmission of HBV in the health care setting has become an increasingly rare event in developed nations. However, it remains a significant risk in developing countries reflecting the higher prevalence of CHB, limited access to HBV vaccination and PEP and a lack of adherence to standard infection control precautions. PMID:22114089

Aspinall, E J; Hawkins, G; Fraser, A; Hutchinson, S J; Goldberg, D

2011-12-01

402

Iron and proinflammatory cytokines in chronic hepatitis C virus infection.  

PubMed

Steatohepatitis is a common finding in chronic hepatitis C virus (HCV) infection. As in other forms of steatohepatitis, oxidative damage may play an outstanding role. However, there are conflicting results relative to the role of iron on hepatic lipogenesis. Proinflammatory cytokines up-regulate ferritin expression, probably reflecting a defensive mechanism against increased oxidative stress, capable to open haem ring and release reactive iron. On the contrary, some adipokines, such as adiponectin, are associated with low ferritin levels. The aim of this study is to analyse the relationships of the amount of liver steatosis with serum iron, transferrin and ferritin as well as with proinflammatory cytokines, such as tumour necrosis factor (TNF)-? and interleukin (IL)-6, and adiponectin levels. We included 82 HCV infected patients and assessed the amount of liver fat by histomorphometry and its relationships with serum iron, ferritin and transferrin, adiponectin and TNF-? and IL-6. Liver steatosis was observed in 67 patients out of 82; in the remaining 15 patients, no steatosis at all was found. Patients with steatosis showed significantly higher serum ferritin levels than patients without steatosis (Z = 2.14; p = 0.032). When patients were classified in quartiles according to the intensity of steatosis, we observed that both TNF-? (KW = 10.6; p = 0.014) and IL-6 (KW = 15.2; p = 0.002) were significantly different among the four groups. Patients with more intense steatosis (highest quartile) showed the highest TNF-? and IL-6 values. Patients with severe hepatitis had higher levels of serum iron than patients with mild to moderate hepatitis. Serum iron also showed a correlation with the proportion of fibrosis (? = 0.30; p = 0.007). Serum iron levels are related with biochemical and histological parameters derived from liver inflammation in HCV-associated liver disease. Serum ferritin is higher among those with intense steatosis and also shows a (non-significant) trend to be associated with the more severe forms of hepatitis. PMID:23892696

López-Prieto, Javier; González-Reimers, Emilio; Alemán-Valls, M Remedios; de la Vega-Prieto, María José; Abreu-González, Pedro; Pelazas-González, Ricardo; Hernández-Luis, Rubén; Jorge-Ripper, Carlos; Santolaria-Fernández, Francisco

2013-10-01

403

Hepatic fibrogenesis requires sympathetic neurotransmitters  

PubMed Central

Background and aims: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. Methods: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. Results: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by ?- and ?-adrenoceptor antagonists. HSC from dopamine ?-hydroxylase deficient (Dbh?/?) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh?/? mice, as evidenced by reduced hepatic accumulation of ?-smooth muscle actin+ve HSC and decreased induction of transforming growth factor ?1 (TGF-?1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-?1 and collagen, and increased liver fibrosis. Conclusions: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis. PMID:14960531

Oben, J A; Roskams, T; Yang, S; Lin, H; Sinelli, N; Torbenson, M; Smedh, U; Moran, T H; Li, Z; Huang, J; Thomas, S A; Diehl, A M

2004-01-01

404

Hepatitis A, B, and C: Learn the Differences  

MedlinePLUS

... caused by the hepatitis B virus (HBV) Hepatitis C caused by the hepatitis C virus (HCV) How ... cause for liver transplant. Hepatitis A, B, and C: Learn the Differences • People who wish to be ...

405

Transmission of hepatitis C virus: Self-limiting hepatitis or chronic hepatitis?  

PubMed Central

It has been suggested that hepatitis C virus (HCV) is selectively transmitted to a new host as an infectious clone from multiple HCV variants (quasispecies) in the donor. Most individuals with HCV infection develop chronic hepatitis, but approximately 15%-40% of them clear the virus spontaneously and the hepatitis is resolved in a self-limiting manner in the acute phase of infection. This difference in the outcome of acute hepatitis C is attributable to both viral characteristics and genetic regulation of infection. In particular, the evolutionary dynamics of the infecting virus and host genetic polymorphisms pertaining mainly to the immune system, including polymorphisms in the region of the Interleukin 28B gene encoding interferon-?-3, are associated with susceptibility to HCV infection. PMID:24222939

Saito, Takafumi; Ueno, Yoshiyuki

2013-01-01

406

Ulnar nerve damage (image)  

MedlinePLUS

... elbow because of elbow fracture or dislocation. The ulnar nerve is near the surface of the body where it crosses the elbow, so prolonged pressure on the elbow or entrapment of the nerve may cause damage. Damage to ...