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1

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 ...

2

Genetic determinants of ethanol-induced liver damage.  

PubMed Central

BACKGROUND: Although a clear correlation exists between cumulative alcohol intake and liver disease, only some of the alcohol abusers develop signs of ethanol-induced liver damage. To identify some of the genetic variations predisposing persons to alcoholic liver disease (ALD), a genetic study was performed in heavy drinkers from the cohort of the Dionysis study, a survey aimed at evaluating liver disease in the open population of two towns in Northern Italy (6917 individuals). MATERIALS AND METHODS: 158 heavy drinkers (approximately 85% of all heavy drinkers in the population; daily alcohol intake > 120 g in males and >60 g in females) were investigated by the analysis of nine polymorphic regions, mapping in exons III and IX of the alcohol-dehydrogenase (ADH)-2 gene, in exon VIII of the ADH3 gene, in intron VI, in the promoter region of the cytochrome P4502E1 (CYP2E1) gene, and in the promoter region of the tumor necrosis factor-alpha gene. RESULTS: Heavy drinkers with or without ALD significantly differed for the distribution of alleles of the cytochrome P4502E1 (CYP2E1) and alcohol-dehydrogenase-3 (ADH-3) genes. In one town, allele C2 in the promoter region of the CYP2E1 gene had a frequency of 0.06 in healthy heavy drinkers, of 0.19 in heavy drinkers with ALD (p = 0.012), and of 0.33 in heavy drinkers with cirrhosis (p = 0.033). In the other town, whose inhabitants have different genetic derivation, a prominent association between ALD and homozygosity for allele ADH3*2 of ADH3 was found, with a prevalence of 0.31 in heavy drinkers with ALD and of 0.07 in healthy heavy drinkers controls (p = 0.004). CONCLUSIONS. Both heterozygosity for allele C2 of CYP2E1 and homozygosity for allele ADH3*2 of ADH3 are independent risk factors for ALD in alcohol abusers. The relative contribution of these genotypes to ALD is dependent on their frequency in the population. Overall, heavy drinkers lacking either of these two genotypes are 3.2 and 4.3 times more protected from developing ALD and cirrhosis respectively. PMID:11471570

Monzoni, A.; Masutti, F.; Saccoccio, G.; Bellentani, S.; Tiribelli, C.; Giacca, M.

2001-01-01

3

Preventive Effect of the Flavonoid, Wogonin, Against Ethanol-Induced Gastric Mucosal Damage in Rats  

Microsoft Academic Search

Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly

Soojin Park; Ki-Baik Hahm; Tae-Young Oh; Joo-Hyun Jin; Ryowon Choue

2004-01-01

4

Ethanol-induced impairment of hepatic glycoprotein secretion in the isolated rat liver perfusion model  

SciTech Connect

The authors have previously shown that acute administration of ethanol inhibits hepatic glycoprotein secretion in vivo. This ethanol-induced effect appears to be mediated by its reactive metabolite, acetaldehyde. Since hormonal influences and vascular changes can not be controlled in vivo during ethanol administration, they investigated the effect of ethanol in the isolated perfused liver model. Rat liver from fed animals was perfused with oxygenated KRB at 3 ml/min/g liver for 4 hrs. Since ethanol inhibits proteins synthesis in vitro, protein acceptor pool size was equalized in both ethanol and control perfused livers with 1 mM cycloheximide. /sup 3/H-glucosamine was used to label hepatic secretory glycoproteins in the perfusate. Colchicine, a known inhibitor of protein secretion, impaired the secretion of labeled glycoproteins with a concomitant retention of these export proteins in the liver; therefore, confirming the authors secretory model. Ethanol (50 mM) inhibited the appearance of glucosamine-labeled glycoproteins by 60% into the perfusate as compared to control livers. Pretreatment of animals with cyanamide (an aldehyde dehydrogenase inhibitor) further potentiated this effect of ethanol in the isolated perfused liver. These data suggest that ethanol inhibits hepatic glycoprotein secretion in the isolated liver perfusion model, and this ethanol-induced impairment appears to be mediated by acetaldehyde.

Volentine, G.D.; Ogden, K.A.; Tuma, D.J.; Sorrell, M.F.

1987-05-01

5

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 60mg/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

6

Asiatic acid from Potentilla chinensis attenuate ethanol-induced hepatic injury via suppression of oxidative stress and Kupffer cell activation.  

PubMed

This study examined the effect of Asiatic acid from Potentilla chinensis (AAPC) on chronic ethanol-induced hepatic injury. Rats underwent intragastric administration of ethanol (5.0–9.0?g/kg) once a day for 12 weeks. A subset of rats were also intragastrically treated with AAPC (2, 4 or 8?mg/kg) once a day. In the end, AAPC treatment significantly protected against ethanol-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases levels and the attenuation of histopathological changes in rats. Additionally, AAPC significantly decreased blood alcohol and acetaldehyde concentrations by enhancing alcohol dehydrogenase and aldehyde dehydrogenase activities. Mechanistically, studies showed that AAPC remarkably alleviated the formations of malondialdehyde and myeloperoxidase, restored impaired antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase, and inhibited cytochrome P450 (CYP)2E1 activity. Moreover, the over-expression of cytokines, such as tumor necrosis factor (TNF)-?, interleukin (IL)-1?, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the elevated plasma endotoxin level and the up-regulated Toll-like receptor 4 (TLR4), CD14 and myeloid differentiation factor 88 (MyD88) as well as nuclear factor-?B were also suppressed by AAPC in ethanol-intoxicated rats. In conclusion, the protective effect of AAPC on ethanol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress and inhibit Kupffer cell activation by decreasing the level of plasma endotoxin and the expression of TLR4, CD14 and MyD88. PMID:24432383

Wei, Jinbin; Huang, Quanfang; Huang, Renbin; Chen, Yongxing; Lv, Shujuan; Wei, Ling; Liang, Chunhong; Liang, Shuang; Zhuo, Lang; Lin, Xing

2013-01-01

7

The role of zinc sulfate and metallothionein in protection against ethanol-induced gastric damage in rats.  

PubMed

In this study, the effects of zinc sulfate against ethanol-induced acute gastric damage in rats were investigated, morphologically and biochemically. In addition, the present investigation has demonstrated the distribution of metallothionein stimulated by zinc in gastric mucosal tissues, immunohistochemically. The gastric damage was induced by intragastric administration of 1 ml absolute ethanol per rat. Rats received zinc sulfate (100 mg/kg/day) for 3 consecutive days 2 hr prior to the administration of absolute ethanol. Acute ethanol exposure caused degenerative morphological changes, a decrease in metallothionein immunreactivity; an increase in lipid peroxidation (LPO) levels, and a decrease in reduced glutathione (GSH) levels in gastric mucosa. On the other hand, zinc sulfate administration to ethanol-treated rats caused a significant reduction in the histological damage, an increase in metallothionein immunreactivity, a decrease in LPO levels, and an increase in GSH levels in gastric mucosa. As a result, the present study indicates that zinc sulfate has a protective effect against ethanol-induced acute gastric damage. In addition, we might say that the zinc given as exogenous protection against acute gastric damage has a protective effect both by stimulation of metallothionein synthesis and through GSH as well as having antioxidative potential. PMID:17103035

Arda-Pirincci, Pelin; Bolkent, Sehnaz; Yanardag, Refiye

2006-12-01

8

Cytoprotective effect of copper(II) complexes against ethanol-induced damage to rat gastric mucosa.  

PubMed

The cytoprotective effect of various copper(II) complexes on the gastric mucosa damage induced by acute intragastric administration of ethanol was investigated. For in vitro experiments, the following copper(II) complexes were tested: Cu(II)(L-Trp)(L-Phe), Cu(II)(L-Leu)Cu(II)(L-Leu-Leu)(L-Leu), Cu(II)(L-Phe-L-Leu), Cu(II)(Gly-His-Lys), and Cu(II)(cyHis)2(ClO4)2. Inorganic copper such as CuSO4 was also tested. The free radical generating system, acting for 2 hr on cardial and fundic mucosa scrapings or mucosal microsomes, was Fe++ (20 microM)/ascorbate (0.25 mM). We found a marked inhibition to 75% of lipid peroxidation in the range 10-100 mM, regardless of whether copper was given in complexed or inorganic form. The results suggest that nontoxic copper(II)-amino acid complexes are able to neutralize oxygen-derived free radicals. In addition, copper(II) complexes suppressed membrane lipid peroxidation when mucosa homogenates were exposed to t-butyl hydroperoxide (1-20 microM) plus Fe++ (50 microM). In vivo experiments on rat stomachs, pretreated p.o. by gavage either with Cu(II)(L-Trp)(L-Phe) as paradigmatic agent or with copper sulphate at equivalent doses in the range 3-30 mg/kg body weight showed a significant decrease (30 min after 95% ethanol administration) in the number and severity of mucosal hemorrhagic lesions. In the gastric mucosa scrapings of copper-treated rats after ethanol exposure, we found that malondialdehyde and conjugated diene levels were unchanged compared to those of untreated controls; five enzyme activities released from lysosomes were near control values. In isolated mucosal cells, whether or not pretreated with 200 microM solution of either Cu(II)(L-Trp)(L-Phe) or CuSO4, the release of cathepsin D activity was also unmodified. The results suggest that the cytoprotective effect of Cu(II) complexes against ethanol-induced mucosal lesions was not associated in vivo to lipid peroxidation. PMID:1619401

Alberghina, M; Lupo, G; La Spina, G; Mangiameli, A; Gulisano, M; Sciotto, D; Rizzarelli, E

1992-03-01

9

Alcohol Dehydrogenase Accentuates Ethanol-Induced Myocardial Dysfunction and Mitochondrial Damage in Mice: Role of Mitochondrial Death Pathway  

PubMed Central

Objectives Binge drinking and alcohol toxicity are often associated with myocardial dysfunction possibly due to accumulation of the ethanol metabolite acetaldehyde although the underlying mechanism is unknown. This study was designed to examine the impact of accelerated ethanol metabolism on myocardial contractility, mitochondrial function and apoptosis using a murine model of cardiac-specific overexpression of alcohol dehydrogenase (ADH). Methods ADH and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Myocardial contractility, mitochondrial damage and apoptosis (death receptor and mitochondrial pathways) were examined. Results Ethanol led to reduced cardiac contractility, enlarged cardiomyocyte, mitochondrial damage and apoptosis, the effects of which were exaggerated by ADH transgene. In particular, ADH exacerbated mitochondrial dysfunction manifested as decreased mitochondrial membrane potential and accumulation of mitochondrial O2•?. Myocardium from ethanol-treated mice displayed enhanced Bax, Caspase-3 and decreased Bcl-2 expression, the effect of which with the exception of Caspase-3 was augmented by ADH. ADH accentuated ethanol-induced increase in the mitochondrial death domain components pro-caspase-9 and cytochrome C in the cytoplasm. Neither ethanol nor ADH affected the expression of ANP, total pro-caspase-9, cytosolic and total pro-caspase-8, TNF-?, Fas receptor, Fas L and cytosolic AIF. Conclusions Taken together, these data suggest that enhanced acetaldehyde production through ADH overexpression following acute ethanol exposure exacerbated ethanol-induced myocardial contractile dysfunction, cardiomyocyte enlargement, mitochondrial damage and apoptosis, indicating a pivotal role of ADH in ethanol-induced cardiac dysfunction possibly through mitochondrial death pathway of apoptosis. PMID:20090911

Guo, Rui; Ren, Jun

2010-01-01

10

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

11

Ethanol-induced changes in hepatic free radical defense mechanisms and fatty-acid composition in the miniature pig.  

PubMed

In the miniature pig, ethanol consumption has been reported to induce alterations in hepatic antioxidant defense capacity, which could result in increased risk of peroxidative damage. However, ethanol may also induce changes in membrane fatty acid composition, which could reduce the risk of peroxidative damage. This study examined lipid peroxidation, antioxidant defense and fatty acid composition in livers from miniature pigs fed ethanol in diets containing 12% of their calories as fat for 20 mo. After 12 and 20 mo of feeding, ethanol-fed pigs had higher hepatic manganese-superoxide dismutase activity, lower hepatic copper concentrations and low hepatic copper-zinc-superoxide dismutase and glutathione peroxidase activities compared with controls. Lipid peroxidation as assessed by thiobarbituric acid reacting substance assay was lower in liver homogenate and mitochondrial and microsomal fractions from ethanol-fed pigs than in controls. The percentage contribution of highly unsaturated fatty acids to total fatty acids in liver homogenates (after 12 mo of feeding) and microsome fractions (after 20 mo of feeding) was lower in the ethanol-fed pigs than in the controls, resulting in a lower peroxidizability index. Ethanol-fed pigs had minimal or no hepatic damage as assessed by histological methods. We suggest that the relative resistance of microsomes to lipid peroxidation is due to the lower peroxidizability index in the ethanol-fed pigs and may account in part for the absence of significant histopathological findings after 20 mo of ethanol feeding. PMID:2050333

Zidenberg-Cherr, S; Olin, K L; Villanueva, J; Tang, A; Phinney, S D; Halsted, C H; Keen, C L

1991-06-01

12

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

13

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

14

Relationships between metal ions and oxygen free radicals in ethanol-induced damage to cultured rat gastric mucosal cells  

Microsoft Academic Search

The current study investigated whether metal ions were cytoprotective against ethanol-induced injury to cultured rat gastric mucosal cellsin vitro. Secondly, the relationships between oxygen free radicals and cytoprotection by metal ions were examined. Cultured cells exposed to ethanol produced superoxide anion, as assessed by reduction of cytochromec, in a time-related fashion, and the production of superoxide anion increased dose-dependently as

Hiroyuki Mutoh; Hideyuki Hiraishi; Shinichi Ota; Akira Terano; Keiji Ogura; Kevin J. Ivey; Tsuneaki Sugimoto

1995-01-01

15

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

16

Tacrolimus (FK506) Prevents Early Stages of Ethanol Induced Hepatic Fibrosis by Targeting LARP6 Dependent Mechanism of Collagen Synthesis  

PubMed Central

Tacrolimus (FK506) is a widely used immunosuppressive drug. Its effects on hepatic fibrosis have been controversial and attributed to immunosuppression. We show that in vitro FK506, inhibited synthesis of type I collagen polypeptides, without affecting expression of collagen mRNAs. In vivo, administration of FK506 at a dose of 4 mg/kg completely prevented development of alcohol/carbon tetrachloride induced liver fibrosis in rats. Activation of hepatic stellate cells (HSCs) was absent in the FK506 treated livers and expression of collagen ?2(I) mRNA was at normal levels. Collagen ?1(I) mRNA was increased in the FK506 treated livers, but this mRNA was not translated into ?1(I) polypeptide. No significant inflammation was associated with the fibrosis model used. FK506 binding protein 3 (FKBP3) is one of cellular proteins which binds FK506 with high affinity. We discovered that FKBP3 interacts with LARP6 and LARP6 is the major regulator of translation and stability of collagen mRNAs. In the presence of FK506 the interaction between FKBP3 and LARP6 is weakened and so is the pull down of collagen mRNAs with FKBP3. We postulate that FK506 inactivates FKBP3 and that lack of interaction of LARP6 and FKBP3 results in aberrant translation of collagen mRNAs and prevention of fibrosis. This is the first report of such activity of FK506 and may renew the interest in using this drug to alleviate hepatic fibrosis. PMID:23755290

Manojlovic, Zarko; Blackmon, John; Stefanovic, Branko

2013-01-01

17

Inhibition of cytochrome P4502E1 by chlormethiazole attenuated acute ethanol-induced fatty liver.  

PubMed

Cytochrome P4502E1 (CYP2E1) has been demonstrated to play crucial roles in chronic ethanol-induced fatty liver, while its role in acute ethanol-induced fatty liver remains unclear. The current study was designed to evaluate the effects of chlormethiazole (CMZ), a specific inhibitor of CYP2E1, on acute ethanol-induced fatty liver, and to explore the mechanisms. Mice were pretreated with single dose of CMZ (50mg/kg body weight) by intraperitoneal injection or equal volume of saline, and then exposed to three doses of ethanol (5g/kg body weight, 25%, w/v) by gavage with 12h intervals. The mice were sacrificed at 4h after the last ethanol dosing. It was found that CMZ significantly attenuated acute ethanol-induced increase of the hepatic and serum triglyceride levels, and reduced fat droplets accumulation in mice liver. Acute ethanol-induced increase of the hepatic malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels (two biomarkers for oxidative stress) and decrease of glutathione (GSH) level was significantly suppressed by CMZ. CMZ also suppressed ethanol-induced decline of serum adiponectin level, but did not significantly affect the serum tumor necrosis factor-? (TNF-?) and ethanol levels. Furthermore, a significant decline of p62 protein level was observed in CMZ/ethanol group mice liver compared with that of the ethanol group mice. However, acute ethanol-induced increase of peroxisome proliferator-activated receptor ? (PPAR-?) protein level was suppressed by CMZ, while the protein levels of sterol regulatory element-binding protein-1c (SREBP-1) and diacylglycerol acyltransferase 2 (DGAT2) were not significantly affected by ethanol or CMZ. Collectively, the results of the current study demonstrated that CMZ could effectively attenuate acute ethanol-induced fatty liver possibly by suppressing oxidative stress and adiponectin decline, and activating autophagy, which suggest that CYP2E1 might also play important roles in acute ethanol-induced fatty liver. PMID:25162931

Chen, Yang-Yang; Zhang, Cui-Li; Zhao, Xiu-Lan; Xie, Ke-Qin; Zeng, Tao

2014-08-24

18

Ethanol-induced acute gastric injury in mast cell-deficient and congenic normal mice. Evidence that mast cells can augment the area of damage.  

PubMed Central

The authors used stereomicroscopy and planimetry to measure the area of glandular stomach mucosa acutely injured by oral ethanol in mast cell-deficient and congenic normal (+/+) mice, and examined the damaged areas in 1-mu sections. Ethanol caused degranulation and/or disruption of gastric mucosal mast cells, and, at certain concentrations of ethanol, mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice developed significantly less (43-90% less) acute gastric injury than either congenic +/+ mice or WBB6F1-W/Wv mice whose mast cells were restored by bone marrow transplantation from WBB6F1-+/+ mice. Nevertheless, ethanol produced detectable, and in some cases substantial, gastric injury even in the complete absence of mast cells. Thus, ethanol can produce some damage to the gastric mucosa independently of mast cells. But these data suggest that under certain circumstances mast cells can augment the area of acute gastric injury induced by ethanol. Images Figure 3 PMID:3605311

Galli, S. J.; Wershil, B. K.; Bose, R.; Walker, P. A.; Szabo, S.

1987-01-01

19

Induction of heat shock proteins and their implication in protection against ethanol-induced damage in cultured guinea pig gastric mucosal cells.  

PubMed

The induction of heat shock proteins in cultured guinea pig gastric mucosal cells was investigated to assess their role in gastric cytoprotection. In response to sublethal heat stress at 43 degrees C for 1 hour, the cells synthesized a 72-kilodalton protein and increased the synthesis of 74- and 90-kilodalton proteins, which were detected using gel electrophoresis after [35S]methionine labeling of the cells. Immunoblot analysis indicated that the 72- and 74-kilodalton proteins were members of the heat shock protein 70 family. Northern blot analysis showed the induction of a 2.6-kilobase messenger RNA of heat shock protein 70 gene only with heat treatment. Furthermore, with heat treatment, there was significant reduction of damage after ethanol treatment. This reduction was blocked with a protein synthesis inhibitor, cycloheximide, and was associated with inhibition of synthesis of heat shock proteins. These results strongly suggest that synthesis of heat shock proteins plays an important role in the intracellular mechanism of gastric protection against ethanol. PMID:2044905

Nakamura, K; Rokutan, K; Marui, N; Aoike, A; Kawai, K

1991-07-01

20

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

21

Lithium protects ethanol-induced neuronal apoptosis  

SciTech Connect

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

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

2006-12-01

22

Specific Conditions for Resveratrol Neuroprotection against Ethanol-Induced Toxicity  

PubMed Central

Aims. 3,5,4?-Trihydroxy-trans-stilbene, a natural polyphenolic compound present in wine and grapes and better known as resveratrol, has free radical scavenging properties and is a potent protector against oxidative stress induced by alcohol metabolism. Today, the mechanism by which ethanol exerts its toxicity is still not well understood, but it is generally considered that free radical generation plays an important role in the appearance of structural and functional alterations in cells. The aim of this study was to evaluate the protective action of resveratrol against ethanol-induced brain cell injury. Methods. Primary cultures of rat astrocytes were exposed to ethanol, with or without a pretreatment with resveratrol. We examined the dose-dependent effects of this resveratrol pretreatment on cytotoxicity and genotoxicity induced by ethanol. Cytotoxicity was assessed using the MTT reduction test. Genotoxicity was evidenced using single cell gel electrophoresis. In addition, DNA staining with fluorescent dyes allowed visualization of nuclear damage using confocal microscopy. Results. Cell pretreatment with low concentrations of trans-resveratrol (0.1–10??M) slowed down cell death and DNA damage induced by ethanol exposure, while higher concentrations (50–100??M) enhanced these same effects. No protection by cis-resveratrol was observed. Conclusion. Protection offered by trans-resveratrol against ethanol-induced neurotoxicity was only effective for low concentrations of this polyphenol. PMID:22778731

Gonthier, Brigitte; Allibe, Nathalie; Cottet-Rousselle, Cécile; Lamarche, Frédéric; Nuiry, Laurence; Barret, Luc

2012-01-01

23

Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C  

PubMed Central

Although the oxidative stress frequently occurs in patients with chronic hepatitis C, its role in future hepatocellular carcinoma (HCC) development is unknown. Hepatic 8-hydroxydeoxyguanosine (8-OHdG) was quantified using liver biopsy samples from 118 naïve patients who underwent liver biopsy from 1995 to 2001. The predictability of 8-OHdG for future HCC development and its relations to epidemiologic, biochemical and histological baseline characteristics were evaluated. During the follow-up period (mean was 6.7±3.3 years), HCC was identified in 36 patients (30.5%). Univariate analysis revealed that 16 variables, including 8-OHdG counts (65.2±20.2 vs 40.0±23.5 cells per 105??m2, P<0.0001), were significantly different between patients with and without HCC. Cox proportional hazard analysis showed that the hepatic 8-OHdG (P=0.0058) and fibrosis (P=0.0181) were independent predicting factors of HCC. Remarkably, 8-OHdG levels were positively correlated with body and hepatic iron storage markers (vs ferritin, P<0.0001 vs hepatic iron score, P<0.0001). This study showed that oxidative DNA damage is associated with increased risk for HCC and hepatic 8-OHdG levels are useful as markers to identify the extreme high-risk subgroup. The strong correlation between hepatic DNA damage and iron overload suggests that the iron content may be a strong mediator of oxidative stress and iron reduction may reduce HCC incidence in patients with chronic hepatitis C. PMID:18231107

Tanaka, H; Fujita, N; Sugimoto, R; Urawa, N; Horiike, S; Kobayashi, Y; Iwasa, M; Ma, N; Kawanishi, S; Watanabe, S; Kaito, M; Takei, Y

2008-01-01

24

Berberine protects liver from ethanol-induced oxidative stress and steatosis in mice.  

PubMed

Alcohol consumption is customary in many cultures and it is a common human behavior worldwide. Binge ethanol and chronic alcohol consumption, two usual drinking patterns of human beings, produce a state of oxidative stress in liver and disturb the liver function. However, a safe and effective therapy for alcoholic liver disease in humans is still elusive. This study identified the natural product berberine as a potential agent for treating or preventing ethanol-induced liver injury. We demonstrated that berberine attenuated oxidative stress resulted from binge drinking in liver by reducing hepatic lipid peroxidation, glutathione exhaust and mitochondrial oxidative damage. Furthermore, berberine also prevented the oxidative stress and macrosteatosis in response to chronic ethanol exposure in mice. Either the total cytochrome P450 2E1 or the mitochondria-located cytochrome P450 2E1, which is implicated in ethanol-mediated oxidative stress, was suppressed by berberine. On the other hand, berberine significantly blunted the lipid accumulation in liver due to chronic alcohol consumption, at least partially, through restoring peroxisome proliferator-activated receptor ?/peroxisome proliferator-activated receptor-gamma Co-activator-1? and hepatocyte nuclear factor 4?/microsomal triglyceride transfer protein pathways. These findings suggested that berberine could serve as a potential agent for preventing or treating human alcoholic liver disease. PMID:25455889

Zhang, Pengcheng; Ma, Dongshen; Wang, Yongchen; Zhang, Miao; Qiang, Xiaoyan; Liao, Min; Liu, Xie; Wu, Hui; Zhang, Yubin

2014-10-16

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

Ethanol-induced oxidative stress: basic knowledge  

PubMed Central

After a general introduction, the main pathways of ethanol metabolism (alcohol dehydrogenase, catalase, coupling of catalase with NADPH oxidase and microsomal ethanol-oxidizing system) are shortly reviewed. The cytochrome P450 isoform (CYP2E1) specifically involved in ethanol oxidation is discussed. The acetaldehyde metabolism and the shift of the NAD/NADH ratio in the cellular environment (reductive stress) are stressed. The toxic effects of acetaldehyde are mentioned. The ethanol-induced oxidative stress: the increased MDA formation by incubated liver preparations, the absorption of conjugated dienes in mitochondrial and microsomal lipids and the decrease in the most unsaturated fatty acids in liver cell membranes are discussed. The formation of carbon-centered (1-hydroxyethyl) and oxygen-centered (hydroxyl) radicals during the metabolism of ethanol is considered: the generation of hydroxyethyl radicals, which occurs likely during the process of univalent reduction of dioxygen, is highlighted and is carried out by ferric cytochrome P450 oxy-complex (P450–Fe3+O2·?) formed during the reduction of heme-oxygen. The ethanol-induced lipid peroxidation has been evaluated, and it has been shown that plasma F2-isoprostanes are increased in ethanol toxicity. PMID:20606811

Signorini, Cinzia; Leoncini, Silvia; Gardi, Concetta; Ciccoli, Lucia; Giardini, Anna; Vecchio, Daniela; Arezzini, Beatrice

2009-01-01

27

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

28

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...

29

Noninvasive assessment of liver damage in chronic hepatitis B  

PubMed Central

AIM: To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index (APRI) and neutrophil-lymphocyte (N/L) ratio to predict liver damage in chronic hepatitis B (CHB). METHODS: We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects. Liver biopsy materials were stained with hematoxylin-eosin and Masson’s trichrome. Patients’ fibrosis scores and histological activity index (HAI) were calculated according to the Ishak scoring system. Fibrosis score was recognized as follows: F0-1 No /early-stage fibrosis, F2-6 significant fibrosis, F0-4 non-cirrhotic and F5-6 cirrhotic. Significant liver ?brosis was de?ned as an Ishak score of ? 2. APRI and N/L ratio calculation was made by blood test results. RESULTS: The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores (P < 0.001). Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count. APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients. However, this significance was not confirmed by multiple logistic regression analysis. The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01 with sensitivity, specificity, positive predictive value and negative predictive value of 62% (36%-86%), 74% (62%-83%), 29% (13%-49%) and 92% (82%-97%), respectively. In addition, correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI (r = -0.218, P = 0.041). CONCLUSION: N/L ratio was negatively correlated with HAI. APRI score may be useful to exclude cirrhosis in CHB patients. PMID:24023983

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

2013-01-01

30

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

NASA Astrophysics Data System (ADS)

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

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

1995-02-01

31

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

32

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

33

Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.  

PubMed

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

34

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.

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

2014-01-01

35

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

36

Ethanol induced impairment of glucose metabolism involves alterations of GABAergic signaling in pancreatic ?-cells.  

PubMed

Alcohol overindulgence is a risk factor of type 2 diabetes mellitus. However, the mechanisms by which alcohol overindulgence damages glucose metabolism remain unclear. Pancreatic islet ?-cells are endowed with type-A ?-aminobutyric acid receptor (GABAAR) mediated autocrine signaling mechanism, which regulates insulin secretion and fine-tunes glucose metabolism. In neurons GABAAR is one of the major targets for alcohol. This study investigated whether ethanol alters glucose metabolism by affecting GABAAR signaling in pancreatic ?-cells. Blood glucose level of test mice was measured using a blood glucose meter. Insulin secretion by the pancreatic ?-cell line INS-1 cells was examined using a specific insulin ELISA kit. Whole-cell patch-clamp recording was used to evaluate GABA-elicited current in INS-1 cells. Western blot and immunostaining were used to measure the expression of GABAAR subunits in mouse pancreatic tissues or in INS-1 cells. Intraperitoneal (i.p.) administration of ethanol (3.0g/kg body weight) to mice altered glucose metabolism, which was associated with decreased expression of GABAAR ?1- and ?- subunits on the surface of pancreatic ?-cells. Acute treatment of cultured INS-1cells with ethanol (60mM) decreased the GABA-induced current and reduced insulin secretion. In contrast, treating INS-1 cells with GABA (100?M) largely prevented the ethanol-induced reduction of insulin release. Importantly, pre-treating mice with GABA (i.p., 1.5mg/kg body weight) partially reversed ethanol-induced impairment of glucose homeostasis in mice. Our data suggest a novel role of pancreatic GABA signaling in protecting pancreatic islet ?-cells from ethanol-induced dysfunction. PMID:25456265

Wang, Shuanglian; Luo, Yan; Feng, Allen; Li, Tao; Yang, Xupeng; Nofech-Mozes, Roy; Yu, Meng; Wang, Changhui; Li, Ziwei; Yi, Fan; Liu, Chuanyong; Lu, Wei-Yang

2014-12-01

37

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

PubMed

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

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

2001-11-01

38

Polymer fraction of Aloe vera exhibits a protective activity on ethanol-induced gastric lesions.  

PubMed

For centuries, Aloe has been used as a herbal plant remedy against skin disorders, diabetes, and for its cardiac stimulatory activity. Here, we examined the gastroprotective effects of an Aloe vera polymer fraction (Avpf; molecular weight cut-off ?50 kDa; 150 mg/kg body weight, p.o.) on an ethanol-induced gastric lesion mouse model. Mice pre-treated with Avpf had significantly fewer gastric lesions than their respective controls. To further examine the potential mechanism underlying this effect, we used reverse transcription-polymerase chain reaction to examine nitric oxide synthase and matrix metalloproteinase (MMP)mRNA expression on tissues from gastric lesions. Our results revealed that the mRNA expressions of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) were each reduced by ~50% in Avpf-treated mice vs. the controls, whereas, the mRNA expression levels of endothelial nitric oxide synthase remained unchanged. MMP-9, an index for gastric lesions, also alleviated the ethanol-treated gastric ulceration during Avpf treatment. These findings collectively suggest that Avpf significantly protects the gastric mucosa against ethanol-induced gastric damage, at least in part, by decreasing mRNA expression levels of not only iNOS and nNOS, but also MMP-9. PMID:21286662

Park, Chul-Hong; Nam, Dong-Yoon; Son, Hyeong-U; Lee, Si-Rim; Lee, Hyun-Jin; Heo, Jin-Chul; Cha, Tae-Yang; Baek, Jin-Hong; Lee, Sang-Han

2011-04-01

39

Protective effects of pogostone from Pogostemonis Herba against ethanol-induced gastric ulcer in rats.  

PubMed

We examined the protective effect of pogostone (PO), a chemical constituent isolated from Pogostemonis Herba, on the ethanol-induced gastric ulcer in rats. Administration of PO at doses of 10, 20 and 40mg/kg body weight prior to ethanol ingestion effectively protected the stomach from ulceration. The gastric lesions were significantly ameliorated by all doses of PO as compared to the vehicle group. Pre-treatment with PO prevented the oxidative damage and the decrease of prostaglandin E2 (PGE2) content. In addition, PO pretreatment markedly increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and decreased gastric malonaldehyde (MDA), relative to the vehicle group. In the mechanistic study, significant elevation of non-protein-sulfhydryl (NP-SH) was observed in the gastric mucosa pretreated by PO. Analysis of serum cytokines indicated that PO pretreatment obviously elevated the decrease of interleukin-10 (IL-10) level, while markedly mitigated the increment of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-?) secretions in ethanol-induced rats. Taken together, these results strongly indicate that PO could exert a gastro-protective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, improvement of antioxidant and anti-inflammatory status, as well as preservation of NP-SH. PMID:25481373

Chen, Haiming; Liao, Huijun; Liu, Yuhong; Zheng, Yifeng; Wu, Xiaoli; Su, Zuqing; Zhang, Xie; Lai, Zhengquan; Lai, Xiaoping; Lin, Zhi-Xiu; Su, Ziren

2015-01-01

40

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 ...

41

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

PubMed

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

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

2012-12-01

42

Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure  

PubMed Central

AIM: Vasodilatation and increased capillary permeability have been proposed to be involved in the pathogenesis of acute and chronic form of hepatic encephalopathy. Prostacyclin (PGI2) and nitric oxide (NO) are important contributors to hyperdynamic circulation in portal hypertensive states. Our previous study showed that chronic inhibition of NO had detrimental effects on the severity of encephalopathy in thioacetamide (TAA)-treated rats due to aggravation of liver damage. To date, there are no detailed data concerning the effects of PGI2 inhibition on the severity of hepatic encephalopathy during fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/(kg.d) for 3 d. Rats were divided into two groups to receive intraperitoneal injection of indomethacin (5 mg/(kg.d), n = 20) or normal saline (N/S, n = 20) for 5 d, starting 2 d before TAA administration. Severity of encephalopathy was assessed by the counts of motor activity measured with Opto-Varimex animal activity meter. Plasma tumor necrosis factor-? (TNF-?, an index of liver injury) and 6-keto-PGF1? (a metabolite of PGI2) levels were measured by enzyme-linked immunosorbent assay. RESULTS: As compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving indomethacin (20% vs 5%, P<0.01). Inhibition of PGI2 created detrimental effects on total movement counts (indomethacin vs N/S: 438±102 vs 841±145 counts/30 min, P<0.05). Rats treated with indomethacin had significant higher plasma levels of TNF-? (indomethacin vs N/S: 22±5 vs 10±1 pg/mL, P<0.05) and lower plasma levels of 6-keto-PGF1? (P<0.001), but not total bilirubin or creatinine (P>0.05), as compared with rats treated with N/S. CONCLUSION: Chronic indomethacin administration has detrimental effects on the severity of encephalopathy in TAA-treated rats and this phenomenon may be attributed to the aggravation of liver injury. This study suggests that PGI2 may provide a protective role in the development of fulminant hepatic failure. PMID:15633222

Chu, Chi-Jen; Hsiao, Ching-Chin; Wang, Teh-Fang; Chan, Cho-Yu; Lee, Fa-Yauh; Chang, Full-Young; Chen, Yi-Chou; Huang, Hui-Chun; Wang, Sun-Sang; Lee, Shou-Dong

2005-01-01

43

Ethanol-induced hepatotoxicity; experimental observations on the role of lipid peroxidation.  

PubMed

Hepatic lipid peroxidation in vivo or in vitro as measured by UV absorption spectra of microsomal lipids or by production of TBA-reacting substances by whole liver homogenates, was studied after acute or during prolonged administration of ethanol. No evidence of peroxidative derangement of liver microsomal lipids in vivo was detected in either experimental situation, while the production of TBA-reacting substances by pooled liver homogenates incubated in vitro appeared slightly increased. Treatment with reduced glutathione (GSH and 2-mercaptopropionylglycine (2-MPG) was able to reduce fatty liver in acute and prolonged ethanol dosing, as well as the production of TBA-reacting compounds. Similar effects were obtained with 3-amino-1,2,4-triazole which was assayed only in acute experiments. By contrast, hepatic triglyceride accumulation induced by a single intoxicating dose of ethanol was not affected by preventive treatment with pyrazole which seemed to act as a pro-oxidant agent as far as the production of TBA-reacting substances is concerned. The role of lipid peroxidation as a pathogenic mechanism for acute and chronic ethanol-induced hepatotoxicity is discussed in relation to the action of anti-oxidant compounds which are active in preventing liver injury. It is concluded that lipid peroxidation is unlikely to be an important mechanism in alcohol hepatotoxicity. PMID:722405

Torrielli, M V; Gabriel, L; Dianzani, M U

1978-09-01

44

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

45

The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats.  

PubMed

This study aims to determine the effects of grape seed and colchicine on carbon tetrachloride (CCl4) induced hepatic damage and on some serum biochemical parameters. Sixty male Wistar albino rats (200-250 g) were randomly divided into six groups (ten rats/group) and included the control group the group were given isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group treated i.p. injection of CCl4 (1.0 mL/kg b.w) in corn oil twice in the first week, Groups 3 and 4 injected with CCl4 as described for group 2 and the rats were orally given (100 mg/kg b.w) GSE and i.p. injected (10 ?g/rat) with colchicine for four weeks, respectively and groups 5 and 6 were the grape seed and colchicine control groups in which rats were orally given grape seed (100 mg/kg b.w) and i.p. injected with colchicine (10 ?g/rat), respectively. Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration, changes ranging from degenerative to necrotic, increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2, treated with CCl4. Histological hepatic changes in the rats in group 3 and 4 were similar to those in group 2. The levels of serum total protein, albumin and globulin decreased in groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT) activities increased. The lowest alkaline phosphatase (ALP) activities were in groups 4 and 5. We concluded that GSE and colchicine have not sufficient ameliorative effects to CCl4 induced acute hepatic damage. PMID:24925249

Atasever, Ayhan; Yaman, Duygu

2014-10-01

46

Dietary high vanadium causes oxidative damage-induced renal and hepatic toxicity in broilers.  

PubMed

The purpose of this study was to investigate the renal and hepatic oxidative damage and toxicity caused by dietary high vanadium in broilers. A total of 420 one-day-old avian broilers were divided into six groups and fed on a corn-soybean basal diet as control diet (vanadium 0.073 mg/kg), and five high vanadium diets (vanadium 5 mg/kg, high vanadium group I; 15 mg/kg, high vanadium group II; 30 mg/kg, high vanadium group III; 45 mg/kg, high vanadium group IV; and 60 mg/kg, high vanadium group V) throughout the experimental period of 42 days. The results showed that the renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, ability to inhibit hydroxy radical, and malondialdehyde (MDA), glutathione, and vanadium contents were not significantly changed in high vanadium group I and II when compared with those of the control groups. However, the SOD and GSH-Px activities, ability to inhibit hydroxy radical, and GSH content were significantly decreased, and the MDA and vanadium contents were markedly increased in high vanadium groups III, IV, and V. At the same time, the lesions were also observed in the kidney and liver of high vanadium groups III, IV, and V. The renal tubular epithelial cells showed granular degeneration and vacuolar degeneration, and hepatocytes showed granular degeneration, vacuolar degeneration, and fatty degeneration. It was concluded that dietary vanadium in the range of 30-60 mg/kg could cause oxidative damage and vanadium accumulation, which induced renal and hepatic toxicity and lesions. The renal and hepatic function was finally impaired in boilers. PMID:21882068

Liu, Juan; Cui, Hengmin; Liu, Xiaodong; Peng, Xi; Deng, Junliang; Zuo, Zhicai; Cui, Wei; Deng, Yuanxin; Wang, Kangping

2012-02-01

47

The effects of daily supplementation of Dendrobium huoshanense polysaccharide on ethanol-induced subacute liver injury in mice by proteomic analysis.  

PubMed

Polysaccharides isolated from edible Dendrobium huoshanense have been shown to possess a hepatoprotection function for selenium- and carbon tetrachloride-induced liver injury. In this study, we investigated the preventive effects of daily supplementation with an homogeneous polysaccharide (DHP) purified from D. huoshanense on ethanol-induced subacute liver injury in mice and its potential mechanisms in liver protection by a proteomic approach. DHP was found to effectively depress the increased ratio of liver weight to body weight, reduce the elevated levels of serum aspartate aminotransferase, total cholesterol, total bilirubin and low density lipoprotein, and alleviate hepatic steatosis in mice with ethanol-induced subacute liver injury. Hepatic proteomics analysis performed by two-dimensional difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) revealed that cystathionine beta-synthase (Cbs) and D-lactate dehydrogenase (Ldhd) were two key proteins regulated by daily DHP intervention, which may assist in correcting the abnormal hepatic methionine metabolism pathway and decreasing the level of hepatic methylglyoxal generated from disordered metabolic pathways caused by ethanol. Our data suggest that DHP can protect liver function from alcoholic injury with complicated molecular mechanisms involving regulation of Cbs and Ldhd. PMID:24933018

Wang, Xiao-Yu; Luo, Jian-Ping; Chen, Rui; Zha, Xue-Qiang; Wang, He

2014-09-01

48

Smokeless tobacco induced increases in hepatic lipid peroxidation, DNA damage and excretion of urinary lipid metabolites.  

PubMed

The possible role of reactive oxygen species in the toxicity of smokeless tobacco (ST) was explored. The effects of an aqueous smokeless tobacco extract (STE) at doses of 125, 250 and 500 mg STE/kg in rats on the induction of hepatic mitochondrial and microsomal lipid peroxidation and the incidence of hepatic nuclear DNA damage 24 hours post treatment were examined. Dose-dependent increases of 1.8, 2.3 and 4.4-fold in mitochondrial and 1.5, 2.1 and 3.6-fold in microsomal lipid peroxidation occurred at 125, 250 and 500 mg STE/kg, respectively, relative to control values. At these same three doses of STE, 1.3, 1.4 and 2.7-fold increases in hepatic DNA single-strand breaks occurred relative to control values. STE administration also resulted in significant increases in excretion of urinary metabolites. Urinary excretion of the four lipid metabolites malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) was monitored by HPLC for 72 hours after treatment of rats with 125 and 250 mg STE/kg. Increases occurred in the excretion of the four lipid metabolites at every dose and time point with maximum increases in the excretion of all lipid metabolites being observed between 12 and 24 hours post treatment. The results suggest the involvement of an oxidative stress in the toxicity of STE. PMID:8086316

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

1994-06-01

49

The effects of splenectomy and glucocorticoids on survival and hepatic uptake of damaged red cells in the mouse.  

PubMed

We have studied the effects of splenectomy and glucocorticoids on the survival and sequestration of Heinz body-containing red blood cells (RBC-HZB). Mice were injected with phenylhydrazine damaged 51Cr labeled isologous red blood cells (RBCs). The spleen removed 36% and the liver 19% of the injected dose after 120 hrs. Red cell survival (T 1/2) fell from 180 hrs for undamaged red cells to 16 hrs for RBC-HZB. Splenectomy resulted in an increase in hepatic uptake of damaged RBCs (36% of the injected dose) and a modest improvement in red cell survival (T 1/2 54 hrs). Treatment of non-splenectomized mice with glucocorticoids reduced the splenic uptake to 16% and the hepatic uptake to 14% of the injected dose. The reduction of splenic upatke was associated with a decrease in splenic mass rather than a decrease in uptake per unit weight of splenic tissue, while reduction in hepatic uptake was associated with both a decrease in hepatic mass and uptake per unit weight. A marked decrease was observed in hepatic uptake and in phagocytosis by Kupffer cells in glucocorticoid-treated splenectomized mice. These data suggest that increased hepatic uptake may decrease the effectiveness of splenectomy in RBC-HZB hemolytic anemia and that glucocorticoids may decrease the hepatic uptake by reducing phagocytosis by Kupffer cells. PMID:602926

Ganick, D J; Segel, G B; Chamberlain, J; Hirsch, L; Klemperer, M R

1977-01-01

50

Isoliquiritigenin attenuates oxidative hepatic damage induced by carbon tetrachloride with or without buthionine sulfoximine.  

PubMed

Glycyrrhizae radix (G. radix) has been demonstrated to have hepatoprotective properties. This study determined the therapeutic effects of isoliquiritigenin (isoLQ) in G. radix, against liver injury induced by CCl4 in rats. CCl4 (0.5 ml/kg/d, twice) or CCl4 plus buthionine sulfoximine exerted severe liver damage assessed by increased plasma levels of alanine aminotransferase and aspartate aminotransferase, in addition to hepatic degeneration and necrosis. These pathological changes were markedly protected by pretreatment with isoLQ (5, 20 mg/kg/d, p.o.) for 3 consecutive days. In addition, pretreatment with isoLQ inhibited CCl4-induced reduction of cytochrome P450 2E1 protein and mRNA expression as well as activity in the liver. Moreover, isoLQ pretreatment reversed the decrease in hepatic antioxidant capacity induced by CCl4 as well as suppressed expression of tumor necrosis factor-alpha and cyclooxigenase-2 in the liver. These results suggest that isoLQ has a protective effect against CCl4-induced liver damage through induction of antioxidant and anti-inflammatory activities. PMID:25450236

Zhao, ZhengLin; Park, Sang Mi; Guan, LiXin; Wu, YiYan; Lee, Jong Rok; Kim, Sang Chan; Kim, Young Woo; Zhao, RongJie

2015-01-01

51

Differential effects of route of T-2 toxin exposure on hepatic oxidative damage in mice.  

PubMed

T-2 toxin is the most toxic among mycotoxins and poses a potential health hazard for both humans and animals. At high doses, T-2 toxin can cause shock-like syndrome that can result in death. We evaluated the effect of time course and route of exposure on hepatic oxidative damage in mice and it is only such study so far to compare the effects of dermal and subcutaneous exposure of T-2 toxin. Mice were exposed to 1 LD50 of T-2 toxin either by percutaneous (5.94 mg/kg body weight) or subcutaneous (1.54 mg/kg body weight) route and sacrificed at 0, 1, 3, and 7 days postexposure. Analysis of a number of serum biochemical variables, antioxidant enzymes activity, gene and protein expression by immunoblot assay showed time and route dependent effects of T-2 induced hepatic oxidative damage. Time dependent increase in protein carbonyl content and protein oxidation was seen in serum and liver. Results of our study may provide possible mechanism for developing medical countermeasures against T-2 toxin. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 64-73, 2015. PMID:23929680

Chaudhary, Manjari; Bhaskar, A S B; Rao, P V Lakshmana

2015-01-01

52

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

53

Hepatic Lipid Partitioning and Liver Damage in Nonalcoholic Fatty Liver Disease  

PubMed Central

Hepatic lipid overloading mainly in the form of triglycerides is considered a prerequisite for the development of nonalcoholic fatty liver disease (NAFLD). However, triglyceride accumulation in the liver in response to lipid overflow may represent a protective mechanism against lipotoxicity. Our aims were to assess the fundamental cellular mechanisms that link lipid compartmentation in hepatocytes to liver damage and disease progression in NAFLD by using both in vivo dietary models of NAFLD and in vitro cell models of lipid overloading. Exposure of murine or human hepatocytes to monounsaturated fatty acids (MUFAs) resulted in lipid accumulation without changes in cell viability. In contrast, cell incubation with saturated fatty acids (SFAs) significantly decreased cell viability and increased caspase activation and apoptosis, with only minor lipid droplet accumulation. Genetic or pharmacological inhibition of stearoyl-CoA desaturase-1 (SCD1), the enzyme that converts SFA to MUFA, sensitized cells to SFA-induced apoptosis. Hepatic SCD1 expression increased in experimental steatosis resulting from high fat diet and decreased in a methionine-choline-deficient (MCD) dietary model of steatohepatitis resulting in the latter situation in significantly increased hepatic SFA levels. SCD1–/– mice on the MCD diet had decreased steatosis and markedly increased hepatocellular apoptosis, liver injury, and fibrosis compared with the SCD1+/+, whereas MUFA feeding prevents the MCD-induced injury. In conclusion, this study suggests hepatic SCD1 plays a key role in prevention of steatohepatitis by partitioning excess lipid into MUFA that can be safely stored. This concept has important implications for the development of novel treatment strategies for patients with this condition. PMID:19119140

Li, Zheng Zheng; Berk, Michael; McIntyre, Thomas M.; Feldstein, Ariel E.

2009-01-01

54

Defective DNA damage response and repair in liver cells expressing hepatitis B virus surface antigen.  

PubMed

Hepatitis B virus (HBV) is implicated in liver cancer. The aim of this study was to find out whether HBV or its components [HBV surface antigen (HBsAg), HBV core protein (HBc), and HBV X protein (HBx)] could interfere with the host DNA damage response and repair pathway. The full HBV genome or individual HBV open-reading frame (ORF) was introduced into HepG2 cells to examine the effect on host genomic stability, DNA repair efficacy in response to double-strand DNA damage, and DNA damage-induced cell death. Responses to apoptosis induction in the HBV ORF-transfected HepG2 cells were also compared with those in HBV-positive and HBV-negative human hepatocellular carcinoma (HCC) cells. In the absence of HBV replication, accumulation of HBsAg in liver cells without other HBV proteins enhanced DNA repair protein and tumor suppressor promyelocytic leukemia (PML) degradation, which resulted in resistance to apoptosis induction and deficient double-strand DNA repair. However, HBsAg-positive cells exhibited increased cell death with exposure to the poly(ADP-ribose) polymerase inhibitor that blocks single-strand DNA repair. These results indicate that suppression of PML by HBsAg disrupts cellular mechanisms that respond to double-strand DNA damage for DNA repair or apoptosis induction, which may facilitate hepatocarcinogenesis and open up a synthetic lethality strategy for HBsAg-positive HCC treatment. PMID:23444429

Chung, Yih-Lin

2013-06-01

55

Promyelocytic leukaemia protein links DNA damage response and repair to hepatitis B virus-related hepatocarcinogenesis.  

PubMed

DNA damage response and repair pathways are important barriers to carcinogenesis. Here, we show that promyelocytic leukaemia (PML, also known as TRIM19), involved in sensing DNA damage and executing homologous recombination repair, is down-regulated in non-tumour liver cells surrounding hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). No PML mutation or deletion was found in HBV-infected liver or HCC cells. Immunohistochemical analysis of liver biopsies from patients with breast or liver cancer and HBV reactivation after chemotherapy revealed PML up-regulation and HBV exacerbation in normal liver tissue in response to DNA damage (functional PML), PML down-regulation in HCC peritumour cells associated with high HBsAg accumulation and low HBV replication activity (suppressive PML), and heterogeneous nuclear PML expression in HCC cells that lost HBV DNA and HBsAg and were non-reactive to DNA damage (dysregulated PML). Loss of PML in HBsAg-transgenic mice promoted chromosome breaks in liver cells and accelerated the accumulation of body and liver fat and the development of a liver steatosis-dysplasia-adenoma-carcinoma sequence in an inflammation-independent and male-predominant manner, compared to PML knock-out or HBsAg-transgenic mice during the same time period. These results indicate that PML deficiency facilitates genomic instability and promotes HBsAg-related hepatocarcinogenesis, which also involves androgen and lipid metabolism. These findings uncover a novel PML link between HBV-related tumourigenesis, DNA repair, and metabolism. PMID:23620081

Chung, Yih-Lin; Wu, Mei-Ling

2013-08-01

56

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

PubMed

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

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

2013-09-01

57

Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells  

PubMed Central

Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are innate immunity sensors that provide an early/effective response to pathogenic or injury conditions. We have reported that ethanol-induced TLR4 activation triggers signaling inflammatory responses in glial cells, causing neuroinflammation and brain damage. However, it is uncertain if ethanol is able to activate NLRs/inflammasome in astroglial cells, which is the mechanism of activation, and whether there is crosstalk between both immune sensors in glial cells. Here we show that chronic ethanol treatment increases the co-localization of caspase-1 with GFAP+ cells, and up-regulates IL-1? and IL-18 in the frontal medial cortex in WT, but not in TLR4 knockout mice. We further show that cultured cortical astrocytes expressed several inflammasomes (NLRP3, AIM2, NLRP1, and IPAF), although NLRP3 mRNA is the predominant form. Ethanol, as ATP and LPS treatments, up-regulates NLRP3 expression, and causes caspase-1 cleavage and the release of IL-1? and IL-18 in astrocytes supernatant. Ethanol-induced NLRP3/caspase-1 activation is mediated by mitochondrial (m) reactive oxygen species (ROS) generation because when using a specific mitochondria ROS scavenger, the mito-TEMPO (500 ?M) or NLRP3 blocking peptide (4 ?g/ml) or a specific caspase-1 inhibitor, Z-YVAD-FMK (10 ?M), abrogates mROS release and reduces the up-regulation of IL-1? and IL-18 induced by ethanol or LPS or ATP. Confocal microscopy studies further confirm that ethanol, ATP or LPS promotes NLRP3/caspase-1 complex recruitment within the mitochondria to promote cell death by caspase-1-mediated pyroptosis, which accounts for ?73% of total cell death (?22%) and the remaining (?25%) die by caspase-3-dependent apoptosis. Suppression of the TLR4 function abrogates most ethanol effects on NLRP3 activation and reduces cell death. These findings suggest that NLRP3 participates, in ethanol-induced neuroinflammation and highlight the NLRP3/TLR4 crosstalk in ethanol-induced brain injury. PMID:25136295

Alfonso-Loeches, Silvia; Ureña-Peralta, Juan R.; Morillo-Bargues, Maria José; Oliver-De La Cruz, Jorge; Guerri, Consuelo

2014-01-01

58

Muscular damage during telbivudine treatment in a chronic hepatitis B patient  

PubMed Central

Summary Muscle tissue damage might be related to metabolic and mechanical factors. Certain drugs have been associated with increased blood levels of creatin phospho kinase (CPK) and myoglobin that are biochemical markers of musculoskeletal damage. An increase of CPK plasma levels might suggest severe rhabdomyolysis with possible resulting renal failure. Telbivudine is an antiviral drug indicated for the treatment of chronic hepatitis B (CHB) in adult patients. An increase in CPK plasma levels has been recently described in some telbivudine-treated CHB patients without muscle-skeletal symptoms. In this paper we report a CHB patient that developed a severe increase of CPK plasma levels during telbivudine-treatment. Pharmacological evaluation, using the Naranjo probability scale, indicated a probable relationship between telbivudine and CPK increase, so telbivudine was discontinued and replaced with entecavir with a complete resolution of laboratory findings. In conclusion, telbivudine treatment can induce muscular damage in the absence of skeletal injury, therefore we suggest to closely monitor the muscular function of the patients treated with this drug in order to prevent possible major complications. PMID:23738248

Caroleo, Benedetto; Galasso, Olimpio; Staltari, Orietta; Giofrè, Chiara; De Sarro, Giovambattista; Guadagnino, Vincenzo; Gallelli, Luca

2011-01-01

59

Muscular damage during telbivudine treatment in a chronic hepatitis B patient.  

PubMed

Muscle tissue damage might be related to metabolic and mechanical factors. Certain drugs have been associated with increased blood levels of creatin phospho kinase (CPK) and myoglobin that are biochemical markers of musculoskeletal damage. An increase of CPK plasma levels might suggest severe rhabdomyolysis with possible resulting renal failure. Telbivudine is an antiviral drug indicated for the treatment of chronic hepatitis B (CHB) in adult patients. An increase in CPK plasma levels has been recently described in some telbivudine-treated CHB patients without muscle-skeletal symptoms. In this paper we report a CHB patient that developed a severe increase of CPK plasma levels during telbivudine-treatment. Pharmacological evaluation, using the Naranjo probability scale, indicated a probable relationship between telbivudine and CPK increase, so telbivudine was discontinued and replaced with entecavir with a complete resolution of laboratory findings. In conclusion, telbivudine treatment can induce muscular damage in the absence of skeletal injury, therefore we suggest to closely monitor the muscular function of the patients treated with this drug in order to prevent possible major complications. PMID:23738248

Caroleo, Benedetto; Galasso, Olimpio; Staltari, Orietta; Giofrè, Chiara; De Sarro, Giovambattista; Guadagnino, Vincenzo; Gallelli, Luca

2011-04-01

60

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

61

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

PubMed Central

The protective effect of red mold rice (RMR) against liver injury in rats fed with a Zn-deficient diet for 12 weeks was investigated in this study. Rats were orally administered RMR (151 mg/kg body weight or 755 mg/kg body weight; 1 × dose or 5 × dose, respectively) with or without Zn once a day for 4 consecutive weeks. The severity of liver damage was evaluated by measuring the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in Zn-deficient rats. RMR significantly inhibited the elevation of serum ALT levels by Zn-deficient induction. Hepatic antioxidase activity was also significantly increased in the RMR + Zn group (RZ), thereby suppressing the productions of reactive oxygen species (ROS) and proinflammatory cytokines in the liver of Zn-deficient rats. These findings suggested that RMR exerted hepatoprotective effects against Zn deficiency-induced liver inflammation. PMID:24716115

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

2012-01-01

62

Potassium permanganate toxicity: A rare case with difficult airway management and hepatic damage.  

PubMed

Potassium permanganate (KMnO4) is rarely used for suicidal attempt. Its ingestion can lead to local as well as systemic toxicities due to coagulation necrosis and damage, caused by free radicals of permanganate. We recently managed a case of suicidal ingestion of KMnO4 in a lethal dose. She had significant narrowing of upper airway leading to difficult intubation as well as hepatic dysfunction and coagulopathy as systemic manifestation. We suggest to keep ourselves ready to handle difficult airway with the aid of fiber optic bronchoscope or surgical airway management in such patients. Upper gastrointestinal (GI) endoscopy should be done at the earliest to determine the extent of upper GI injury and further nutrition planning. PMID:25538417

Agrawal, Vijay Kumar; Bansal, Abhishek; Kumar, Ranjeet; Kumawat, Bhanwar Lal; Mahajan, Parul

2014-12-01

63

Potassium permanganate toxicity: A rare case with difficult airway management and hepatic damage  

PubMed Central

Potassium permanganate (KMnO4) is rarely used for suicidal attempt. Its ingestion can lead to local as well as systemic toxicities due to coagulation necrosis and damage, caused by free radicals of permanganate. We recently managed a case of suicidal ingestion of KMnO4 in a lethal dose. She had significant narrowing of upper airway leading to difficult intubation as well as hepatic dysfunction and coagulopathy as systemic manifestation. We suggest to keep ourselves ready to handle difficult airway with the aid of fiber optic bronchoscope or surgical airway management in such patients. Upper gastrointestinal (GI) endoscopy should be done at the earliest to determine the extent of upper GI injury and further nutrition planning.

Agrawal, Vijay Kumar; Bansal, Abhishek; Kumar, Ranjeet; Kumawat, Bhanwar Lal; Mahajan, Parul

2014-01-01

64

Hepatitis  

MedlinePLUS

... be serious. Some can lead to scarring, called cirrhosis, or to liver cancer. Sometimes hepatitis goes away by itself. If it does not, it can be treated with drugs. Sometimes hepatitis lasts a lifetime. Vaccines can help prevent some viral forms.

65

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

PubMed

To find out the active principles against ethanol-induced toxicity in mice, Andrographis paniculata Nees. (Ap) was chosen and isolated andrographolide (ANDRO) and arabinogalactan proteins (AGPs). ANDRO was detected by HPTLC, FTIR and quantified by HPLC (10mg/g of Ap powder). AGPs was detected by beta-glucosyl Yariv staining of SDS-PAGE gel, FTIR and quantified by single radial gel diffusion assay with beta-glucosyl Yariv reagent (0.5mg/g Ap powder). The mice are pretreated intra-peritoneally (i.p.) with different doses (62.5, 125, 250, and 500mg/kg) of body weight of mice] of ANDRO and AGPs for 7 days and then ethanol (7.5g/kg of body weight) was injected, i.p. Besides, silymarin was used as standard hepatoprotective agent for comparative study with ANDRO and AGPs. The ameliorative activity of ANDRO and AGP against hepatic renal alcohol toxicity was measured by assessing GOT, GPT, ACP, ALP and LP levels in liver and kidney. It has been observed that pretreatment of mice with ANDRO and AGPs at 500mg/kg of body weight and 125mg/kg of body weight respectively could able to minimize the toxicity in compare to ethanol treated group as revealed by the different enzymatic assay in liver and kidney tissues and the results were comparable with silymarin. Hence, out of several ill-defined compounds present in Ap, ANDRO and AGPs are the potential bioactive compounds responsible for protection against ethanol-induced toxicity. PMID:17127022

Singha, Prajjal K; Roy, Somenath; Dey, Satyahari

2007-04-20

66

Effect of Picroliv on cadmium-induced hepatic and renal damage in the rat.  

PubMed

The therapeutic efficacy of Picroliv--a standardized extract of Picrorhiza kurroa--was investigated in male rats exposed to CdCl2 (0.5 mg/kg, sc), 5 days/week for 18 weeks. Picroliv at two doses (6 and 12 mg/kg, po) was given to the cadmium (Cd)-administered group for the last 4 weeks (i.e., weeks 15-18). The Cd altered oxidative stress indices, such as increased lipid peroxidation and membrane fluidity, reduced levels of non-protein sulphydryls (NPSHs), and Na+K+ATPase activity in the liver and kidney were found close to the control values by Picroliv treatment, suggesting its antioxidant potential. The hepatoprotective action of Picroliv was evident by its ability to lower the Cd-induced liver function parameters--the serum enzymes, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH). Bile flow and biliary Cd also increased as a result of Picroliv's choleretic property. The Cd-induced serum urea and urinary excretion of proteins, calcium (Ca), Cd and enzymes, such as N-acetyl-beta-D-glucosaminidase (NAG) and LDH, were less marked on Picroliv treatment, indicating recovery from nephrotoxicity. Organ uptake of Cd and essential metals by Cd exposure was reduced on Picroliv treatment. Cd-induced hepatic metallothionein (MT) was lowered by Picroliv, whereas renal MT was unaltered. Cd-induced hepatic damage was also minimized. However, the renal morphological changes were marginally protected by Picroliv. The 12-mg Picroliv dose was more effective than the 6-mg dose in causing amelioration of the above parameters. This study has provided clear evidence for the hepato- and renal protective efficacy of Picroliv against experimental Cd toxicity. PMID:17165624

Yadav, N; Khandelwal, S

2006-10-01

67

The effects of caloric restriction against ethanol-induced oxidative and nitrosative cardiotoxicity and plasma lipids in rats.  

PubMed

Caloric restriction (CR) prevents or delays a wide range of aging-related diseases possibly through alleviation of oxidative stress. The aim of our study was to examine the effect of CR on oxidative and nitrosative cardiac damage in rats, induced by acute ethanol intoxication. Male Wistar rats were divided into following groups: control; calorie-restricted groups with intake of 60-70% (CR60-70) and 40-50% of daily energy needs (CR40-50); ethanol-treated group (E); calorie-restricted, ethanol-treated groups (CR60-70?+?E, CR40-50?+?E). Ethanol was administered in five doses of 2?g/kg every 12?h, while the duration of CR was five weeks before ethanol treatment. Malondialdehyde level was significantly lower in CR60-70?+?E and significantly higher in CR40-50?+?E vs. control. Nitrite and nitrate level was significantly higher in CR40-50?+?E compared to control group. Activity of total superoxide dismutase (SOD) and its isoenzyme, copper/zinc-SOD (Cu/ZnSOD), was significantly higher in CR60-70?+?E and lower in CR40-50?+?E vs. control. Activity of manganese-SOD (MnSOD), that is also SOD isoenzyme, was significantly lower in ?CR40-50 + E compared to control group. Plasma content of sulfhydryl (SH) groups was significantly higher in CR60-70 group vs. control. Plasma concentration of total cholesterol, triacylglycerol, low-density lipoproteins and high-density lipoproteins was significantly lower in CR60-70 group compared to control values. Food restriction to 60-70% of daily energy needs has a protective effect on acute ethanol-induced oxidative and nitrosative cardiac damage, at least partly due to alleviation of ethanol-induced decrease in SOD activity, while restriction to 40-50% of energy needs aggravates lipid peroxidation and nitrosative stress. PMID:24157589

Vucevic, Danijela; Mladenovic, Dusan; Ninkovic, Milica; Aleksic, Vuk; Stankovic, Milena N; Stankovic, Marija; Jorgacevic, Bojan; Vukicevic, Rada Jesic; Radosavljevic, Tatjana

2013-12-01

68

Hepatitis  

MedlinePLUS

... partner. Increased rates of hepatitis A infection among gay and bisexual men have been reported in many ... by many physicians with a large number of gay and bisexual male patients. As with all STDs, ...

69

The influence of enteral nutrition on gut barrier in the post-operative patients with damaged hepatic function.  

PubMed

The safety, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the clinical implication studied. Seventy-six adult patients whose hepatic function were in Child B or C grade were randomly assigned in EN group (30 cases), total parenteral nutrition (TPN) group (26 cases) and control group (CON, 20 cases). The patients received different nutritional support. The signs of nutritional condition and hepatic function were messured at 1 day before, 5 days and 10 days after the surgical operation respectively. The changes in the urine lactulose (L) and mannitol (M) contents and L/M ratio were observed by using pulsed electrochemical detection (HPLC-PED) to acquire the different effects among the different nutritional support performance. The results showed that the patients in the EN group and TPN group had no worse hepatic function damage after operation. The patients in the EN group reached the positive nitrogen balance earlier, had a less weight loss than in the TPN group with the difference being significant (P < 0.05). There was no obvious change in L/M ratio in the postoperative patients in the EN group (P > 0.05), but there was significant difference in L/M between TPN group and CON group (P < 0.05). It was concluded that EN was a rational, safe, effective and practical nutrition support method in the patients with damaged hepatic function patients after surgical operation and EN can effectively protect the structure and function of gut barrier from sever infection. PMID:12539560

Zheng, Q; Hu, Q

2001-01-01

70

Garcinia kola seed ameliorates renal, hepatic, and testicular oxidative damage in streptozotocin-induced diabetic rats.  

PubMed

Abstract Context: In Africa, Garcinia kola Heckel (Guttiferae) seed is commonly recommended in folklore medicine for the treatment of diabetes and its associated complications. Objective: The present study evaluated this traditional claim by mechanistic investigation into the effect of G. kola seed administration on renal, hepatic, and testicular oxidative damage in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Diabetes mellitus was induced in adult male Wistar rats by an intraperitoneal injection of STZ (50?mg/kg). The diabetic rats were thereafter treated orally once per day with G. kola seed (250?mg/kg) and monitored for 14?d. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress indices, sperm characteristics, and histopathological examination of the kidney, liver, and testes were evaluated to monitor treatment-related effects of G. kola seed in STZ-induced diabetic rats. Results and discussion: Garcinia kola seed administration significantly ameliorated hyperglycemia mediated damage by decreasing the blood glucose level (72.8% and 84.6% on the 7th and 14th post-treatment days, respectively), enhancement of the antioxidant system, inhibition of lipid peroxidation, and improving the architecture of the kidney, liver, and testes in STZ-induced diabetic rats. In addition, G. kola seed intervention restored the kidney and liver function biomarkers, the sperm characteristics as well as the plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, triiodothyronine (T3), and thyroxine (T4) to normal in STZ-induced diabetic rats. Conclusion: The findings from this investigation provide persuasive scientific support for the traditional use of G. kola seed in the treatment of diabetes and its associated complications. PMID:25243878

Adedara, Isaac A; Awogbindin, Ifeoluwa O; Anamelechi, Joy P; Farombi, Ebenezer O

2014-09-22

71

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

72

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

73

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

74

Hepatoprotective and antioxidant activities of Vernonia amygdalina on acetaminophen-induced hepatic damage in mice.  

PubMed

Vernonia amygdalina Del. (Family Compositae) is used in Nigerian folk medicine as a tonic and remedy against constipation, fever, high blood pressure, and many infectious diseases. We have evaluated the hepatoprotective and antioxidant effects of an aqueous extract of V. amygdalina leaves against acetaminophen-induced hepatotoxicity and oxidative stress in mice in vivo. Activities of liver marker enzymes in serum (glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, lactate dehydrogenase, and alkaline phosphatase) and bilirubin levels were determined colorimetrically, while catalase activity, lipid peroxidation products, thiobarbituric acid-reactive substances (TBARS), iron, and total protein concentrations were measured in liver homogenate. Acetaminophen challenge (300 mg/kg, i.p) for 7 days caused significant (P < .01) increases in the levels of bilirubin, liver enzymes, TBARS, and iron, while catalase activity and total protein level were reduced significantly (P < .01). Preadministration of V. amygdalina resulted in a dose-dependent (50-100 mg/kg) reversal of acetaminophen-induced alterations of all the liver function parameters by 51.9-84.9%. Suppression of acetaminophen-induced lipid peroxidation and oxidative stress by the extract was also dose-dependent (50-100 mg/kg). The results of this study suggest that V. amygdalina elicits hepatoprotectivity through antioxidant activity on acetaminophen-induced hepatic damage in mice. PMID:17201640

Iwalokun, B A; Efedede, B U; Alabi-Sofunde, J A; Oduala, T; Magbagbeola, O A; Akinwande, A I

2006-01-01

75

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

76

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

77

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

78

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

79

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

80

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

81

Zinc inhibits ethanol-induced HepG2 cell apoptosis.  

PubMed

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

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

2008-05-15

82

Zinc inhibits ethanol-induced HepG2 cell apoptosis  

SciTech Connect

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

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

2008-05-15

83

Drug-induced hepatitis  

MedlinePLUS

Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

84

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

SciTech Connect

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

Wu Hai [University of Texas Medical Branch, Department of Pathology, 3 118A Keiller Building, Galveston, TX 77555 (United States); Cai Ping [University of Texas Medical Branch, Department of Pathology, 3 118A Keiller Building, Galveston, TX 77555 (United States); Clemens, Dahn L. [Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Jerrells, Thomas R. [Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Ansari, G.A. Shakeel [University of Texas Medical Branch, Department of Pathology, 3 118A Keiller Building, Galveston, TX 77555 (United States); Kaphalia, Bhupendra S. [University of Texas Medical Branch, Department of Pathology, 3 118A Keiller Building, Galveston, TX 77555 (United States)]. E-mail: bkaphali@utmb.edu

2006-10-15

85

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

86

Protective effect of Mesona procumbens against tert-butyl hydroperoxide-induced acute hepatic damage in rats.  

PubMed

The protective effect of Hsian-tsao (Mesona procumbens Hemsl.) and its active compounds on liver damage was evaluated using the model of tert-butyl hydroperoxide (t-BHP)-induced acute hepatic damage in rats. Male Sprague-Dawley rats (200 +/- 10 g) were orally pretreated with a water extract of Hsian-tsao (WEHT) (0.1, 0.5, and 1.0 g/kg) or caffeic acid (0.1 g/kg of body weight) for 13 days before a single dose of t-BHP (0.2 mmol/kg, intraperitoneally) to each animal, and the rats were sacrificed 18 h later by decapitation; blood samples were collected for the assays of serum biochemical values. The livers were excised from the animals and assayed for oxidative injury, antioxidant enzyme, and pathological histology. The result showed that the oral pretreatment of WEHT (0.1, 0.5, and 1.0 g/kg) or caffeic acid (0.10 g/kg) before t-BHP (0.2 mmol/kg) treatment significantly lowered the serum levels of the hepatic enzyme markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) and reduced oxidative stress of the liver by evaluation of malondialdehyde, glutathione, 8-hydroxy-2'-deoxyguanosine, glutathione peroxidase, and glutathione reductase. The histopathological evaluation of the rat livers showed that WEHT and caffeic acid reduced the incidence of liver lesions including cloudy swelling, pyknosis, and cytolysis induced by t-BHP in rats. On the basis of the results of this study, it can be speculated that M. procumbens protects liver against t-BHP-induced hepatic damage in rats. PMID:15212457

Yen, Gow-Chin; Yeh, Chi-Tai; Chen, Yen-Ju

2004-06-30

87

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

88

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

PubMed Central

Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper/T-cytotoxic type-1 cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1?; MIP-1?), CCL4 (MIP-1?), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-??inducible protein-10; IP-10), CXCL11 (interferon-inducible T-cell ? chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon ?; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver. PMID:19084927

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

2008-01-01

89

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

PubMed

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

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

2006-09-01

90

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

91

Varenicline ameliorates ethanol-induced deficits in learning in C57BL\\/6 mice  

Microsoft Academic Search

Ethanol is a frequently abused drug that impairs cognitive processes such as learning. Varenicline, an ?4?2 nicotinic receptor partial agonist and ?7 nicotinic receptor full agonist prescribed for smoking cessation, has been shown to decrease ethanol consumption. The current study investigated whether varenicline could ameliorate ethanol-induced deficits in learning and whether varenicline alters blood alcohol concentration in C57BL\\/6 mice. Conditioning

Danielle Gulick; Thomas J. Gould

2008-01-01

92

Zinc inhibits ethanol-induced HepG2 cell apoptosis  

Microsoft Academic Search

Alcohol consumption produces a variety of metabolic alterations in liver cells, associated with ethanol oxidation and with nonoxidative metabolism of ethanol, among others apoptosis of hepatocytes. As zinc is known as a potent antioxidant and an inhibitor of cell apoptosis, the aim of this paper was to investigate whether zinc supplementation could inhibit ethanol-induced HepG2 apoptosis, and whether this inhibition

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

2008-01-01

93

Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.  

PubMed

Recent work suggests that stomach-derived hormone ghrelin receptor (GHS-R1A) antagonism may reduce motivational aspects of ethanol intake. In the current study we hypothesized that the endogenous GHS-R1A agonist ghrelin modulates alcohol reward mechanisms. For this purpose ethanol-induced conditioned place preference (CPP), ethanol-induced locomotor stimulation and voluntary ethanol consumption in a two-bottle choice drinking paradigm were examined under conditions where ghrelin and its receptor were blocked, either using ghrelin knockout (KO) mice or the specific ghrelin receptor (GHS-R1A) antagonist "JMV2959". We showed that ghrelin KO mice displayed lower ethanol-induced CPP than their wild-type (WT) littermates. Consistently, when injected during CPP-acquisition, JMV2959 reduced CPP-expression in C57BL/6 mice. In addition, ethanol-induced locomotor stimulation was lower in ghrelin KO mice. Moreover, GHS-R1A blockade, using JMV2959, reduced alcohol-stimulated locomotion only in WT but not in ghrelin KO mice. When alcohol consumption and preference were assessed using the two-bottle choice test, both genetic deletion of ghrelin and pharmacological antagonism of the GHS-R1A (JMV2959) reduced voluntary alcohol consumption and preference. Finally, JMV2959-induced reduction of alcohol intake was only observed in WT but not in ghrelin KO mice. Taken together, these results suggest that ghrelin neurotransmission is necessary for the stimulatory effect of ethanol to occur, whereas lack of ghrelin leads to changes that reduce the voluntary intake as well as conditioned reward by ethanol. Our findings reveal a major, novel role for ghrelin in mediating ethanol behavior, and add to growing evidence that ghrelin is a key mediator of the effects of multiple abused drugs. PMID:23428971

Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M

2013-05-01

94

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

PubMed

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

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

2005-01-01

95

A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion.  

PubMed Central

The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication. Ethanol was administered over a 2-h period during which blood ethanol levels remained stably elevated. We report that intravenous administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completely prevented by instillation of trypsin into the duodenum or by lavage of the duodenum with saline during ethanol administration. Furthermore, the intraduodenal activity of a CCK-releasing factor is increased by infusion of ethanol. These studies indicate that administration of ethanol causes rat pancreatic exocrine secretion to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events which link ethanol abuse to the development of pancreatic injury. PMID:9022085

Saluja, A K; Lu, L; Yamaguchi, Y; Hofbauer, B; Rünzi, M; Dawra, R; Bhatia, M; Steer, M L

1997-01-01

96

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

97

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

98

Effect of magnesium on calcium-dependent brain function that prolongs ethanol-induced sleeping time in mice  

Microsoft Academic Search

The effect of intracerebroventricular (i.c.v.) administration of magnesium on calcium- and dopamine-dependent brain function was investigated behaviorally and biochemically. The duration of ethanol-induced sleeping time in mice was prolonged following i.c.v. administration of calcium chloride (10?mol\\/kg) or dopamine (30nmol\\/mouse); however, it was not affected by magnesium chloride (10 or 40?mol\\/kg). The ability of calcium to prolong ethanol-induced sleeping time was

Den'etsu Sutoo; Kayo Akiyama

2000-01-01

99

Modelling ethanol-induced sleeping time in inbred strains of mice : A repeated measures design with left-censored data  

Microsoft Academic Search

In this paper we present a repeated measures analysis of ethanol-induced anesthesia (sleeping time) in mice from the inbred long-sleep (ILS) and short-sleep (ISS) strains of mice and their derived F1 and F2 generations. Due to the difficulty in the assessment of ethanol-induced sleeping time, some of the measurements are left-censored by a fixed detection limit of 1 min. Furthermore

Roel Braekers; Paul Markel

100

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

101

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

102

Effect of green tea and (-)-epigallocatechin gallate on ethanol-induced toxicity in HepG2 cells.  

PubMed

Despite the continuing reports supporting the hepatoprotective effects of green tea against ethanol intoxication, there remain controversies regarding the active compound(s) and molecular mechanism. These issues were addressed in the present study using cultured HepG2 cells exposed to a lethal dose of ethanol. Gamma-glutamyl transferase (GGT) was chosen as a marker of ethanol toxicity because it is widely used in clinics. When the cells were treated with ethanol at various concentrations, there was a dose-dependent increase of GGT activity in the culture media and loss of cell viability. Pretreatment of the cells with green tea extract attenuated the changes significantly. Among the green tea constituents, (-)-epigallocatechin gallate (EGCG) attenuated the ethanol cytotoxicity effectively, whereas L-theanine and caffeine had no effects. The ethanol cytotoxicity was also attenuated by alcohol dehydrogenase inhibitor 4-methyl pyrazol and GGT inhibitor acivicin as well as by thiol modulators such as S-adenosyl-L-methionine, N-acetyl-L-cysteine and glutathione. EGCG failed to prevent the intracellular glutathione loss caused by ethanol, but it appeared to be a strong GGT inhibitor. Therefore the cytoprotective effects of green tea could be attributed to the inhibition of GGT activity by EGCG. This study suggests that GGT inhibitors including EGCG may provide a novel strategy for attenuating ethanol-induced liver damage. PMID:18350509

Lee, Sang Il; Kim, Hyo Jung; Boo, Yong Chool

2008-05-01

103

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

104

The protective effects of cerium oxide nanoparticles against hepatic oxidative damage induced by monocrotaline  

PubMed Central

Objective The objective of the present study was to determine the ability of cerium oxide (CeO2) nanoparticles to protect against monocrotaline (MCT)-induced hepatotoxicity in a rat model. Method Twenty male Sprague Dawley rats were arbitrarily assigned to four groups: control (received saline), CeO2 (given 0.0001 nmol/kg intraperitoneally [IP]), MCT (given 10 mg/kg body weight IP as a single dose), and MCT + CeO2 (received CeO2 both before and after MCT). Electron microscopic imaging of the rat livers was carried out, and hepatic total glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) enzymatic activities were quantified. Results Results showed a significant MCT-induced decrease in total hepatic GSH, GPX, GR, and GST normalized to control values with concurrent CeO2 administration. In addition, MCT produced significant increases in hepatic CAT and SOD activities, which also ameliorated with CeO2. Conclusions These results indicate that CeO2 acts as a putative novel and effective hepatoprotective agent against MCT-induced hepatotoxicity. PMID:21289991

Amin, Kamal A; Hassan, Mohamed S; Awad, El-Said T; Hashem, Khalid S

2011-01-01

105

Early termination of immune tolerance state of hepatitis B virus infection explains liver damage  

PubMed Central

AIM: To assess an early termination of immune tolerance state of chronic hepatitis B virus infection in Bangladesh and its clinical significance. METHODS: From a series of 167 treatment-naive chronic hepatitis B patients aged between 12 to 20 years (mean ± SD; 17.5 ± 2.8 years), percutaneous liver biopsies of 89 patients who were all hepatitis B e antigen negative at presentation were done. Of them, 81 were included in the study. They had persistently normal or raised serum alanine aminotransferase (ALT) values. A precore mutation (PCM) study was accomplished in 8 patients who were randomly selected. RESULTS: Forty-four (53.7%) patients had significant necroinflammation (HAI-NI > 7), while significant fibrosis (HAI-F ? 3) was seen in 15 (18.5%) patients. Serum ALT (cut off 42 U/L) was raised in 29 (35.8%) patients, while low HBV DNA load (< 105 copies/mL) was observed in 57 (70.4%) patients. PCM was negative in all 8 patients. CONCLUSION: This study indicates that the current concept of age-related immune tolerance state of HBV infection deserves further analyses in different population groups. PMID:25232455

Mamun-Al-Mahtab; Akbar, Sheikh Mohammad Fazle; Uddin, Helal; Khan, Sakirul Islam; Rahman, Salimur

2014-01-01

106

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

Microsoft Academic Search

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

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

2005-01-01

107

Gastroprotective effect of taurine zinc solid dispersions against absolute ethanol-induced gastric lesions is mediated by enhancement of antioxidant activity and endogenous PGE2 production and attenuation of NO production.  

PubMed

Zinc plays a key role in maintaining gastric mucosal integrity, while alcohol dependency can lead to low zinc status. Complexes containing zinc have been reported to have better ability to protect gastric mucosa than the compounds alone. In this study, taurine zinc [Zn(NH3CH2CH2SO3)2] solid dispersions (SDs) were synthesized and investigated in an ethanol-induced ulcer model in rats. Gastric ulcer index; gastric mucosa malondialdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase (SOD) activity and prostaglandin E2 (PGE2) production; and serum nitric oxide (NO) were assessed and histological analysis of the gastric mucosa tissue was performed. Taurine zinc (100, 200 mg/kg) SDs protected rat gastric mucosa from ethanol-induced injury. Moreover, the gastroprotective effect of taurine zinc SDs was accompanied by a decrease in serum NO and significant increase in gastric prostaglandin E2 (PGE2). When indomethacin, a non-selective COX inhibitor was administered before the last dose of taurine zinc, the gastroprotective effect of taurine zinc was weakened. Furthermore, taurine zinc (200 mg/kg) SDs protected against ulceration more significantly than the same dose of taurine alone, suggesting a synergistic effect between taurine and zinc. These results indicate taurine zinc protects the gastric mucosa against ethanol-induced damage by elevating antioxidants, decreasing lipid peroxidation and inhibiting the production of nitric oxide. The gastroprotective effect of taurine zinc was also partially mediated by endogenous PGE2 production. PMID:25041839

Yu, Chuan; Mei, Xue-Ting; Zheng, Yan-Ping; Xu, Dong-Hui

2014-10-01

108

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

109

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

PubMed Central

Background Cytochrome P4502E1 (CYP2E1) has been suggested to play critical roles in the pathogenesis of alcoholic fatty liver (AFL), but the underlying mechanisms remains unclear. The current study was designed to evaluate whether CYP2E1 suppression by chlormethiazole (CMZ) could suppress AFL in mice, and to explore the underlying mechanisms. Methods Mice were treated with or without CMZ (50 mg/kg bw, i.p.) and subjected to liquid diet with or without ethanol (5%, w/v) for 4 weeks. Biochemical parameters were measured using commercial kits. The protein and mRNA levels were detected by western blot and qPCR, respectively. Histopathology and immunohistochemical assay were performed with routine methods. Results CYP2E1 inhibition by CMZ completely blocked AFL in mice, shown as the decline of the hepatic and serum triglyceride levels, and the fewer fat droplets in the liver sections. Chronic ethanol exposure led to significant decrease of the mRNA and protein levels of peroxisome proliferator-activated receptor ? (PPAR-?), which was blocked by CMZ co-treatment. CMZ co-treatment suppressed ethanol-induced oxidative stress, overproduction of tumor necrosis ? (TNF-?), and decrease of protein levels of the PPAR-? co-activators including p300 and deacetylated PGC1-?. Furthermore, CMZ co-treatment led to the activation of AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), and PI3K/Akt/GSK3? pathway. However, chronic ethanol-induced decline of acyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) protein levels was partially restored by CMZ, while the activation of autophagy appeared to be suppressed by CMZ. Conclusion These results suggested that CMZ suppressed chronic ethanol-induced oxidative stress, TNF-? overproduction, decline of p300 protein level and deacetylation of PGC1-?, and activated AMPK, MAPK, and PI3K/Akt/GSK3? pathway, which might contribute to the activation of PPAR-? and account for the protection of CMZ against AFL. PMID:24892905

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

2014-01-01

110

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

111

Fractalkine is a “find-me” signal released by neurons undergoing ethanol-induced apoptosis  

PubMed Central

Apoptotic neurons generated during normal brain development or secondary to pathologic insults are efficiently cleared from the central nervous system. Several soluble factors, including nucleotides, cytokines, and chemokines are released from injured neurons, signaling microglia to find and clear debris. One such chemokine that serves as a neuronal–microglial communication factor is fractalkine, with roles demonstrated in several models of adult neurological disorders. Lacking, however, are studies investigating roles for fractalkine in perinatal brain injury, an important clinical problem with no effective therapies. We used a well-characterized mouse model of ethanol-induced apoptosis to assess the role of fractalkine in neuronal–microglial signaling. Quantification of apoptotic debris in fractalkine-knockout (KO) and CX3CR1-KO mice following ethanol treatment revealed increased apoptotic bodies compared to wild type mice. Ethanol-induced injury led to release of soluble, extracellular fractalkine. The extracellular media harvested from apoptotic brains induces microglial migration in a fractalkine-dependent manner that is prevented by neutralization of fractalkine with a blocking antibody or by deficiency in the receptor, CX3CR1. This suggests fractalkine acts as a “find-me” signal, recruiting microglial processes toward apoptotic cells to promote their clearance. Next, we aimed to determine whether there are downstream alterations in cytokine gene expression due to fractalkine signaling. We examined mRNA expression in fractalkine-KO and CX3CR1-KO mice after alcohol-induced apoptosis and found differences in cytokine production in the brains of these KOs by 6 h after ethanol treatment. Collectively, this suggests that fractalkine acts as a “find me” signal released by apoptotic neurons, and subsequently plays a critical role in modulating both clearance and inflammatory cytokine gene expression after ethanol-induced apoptosis. PMID:25426022

Sokolowski, Jennifer D.; Chabanon-Hicks, Chloe N.; Han, Claudia Z.; Heffron, Daniel S.; Mandell, James W.

2014-01-01

112

Insulin attenuates the acquisition and expression of ethanol-induced locomotor sensitization in DBA/2J mice  

PubMed Central

Aims Ethanol-induced locomotor sensitization is a behavioral manifestation of physiological responses to repeated ethanol exposures. While ethanol exerts direct effects on multiple neurotransmitter systems in the brain, ethanol-induced changes in metabolic state, including acute hyperglycemia and inhibition of insulin signaling, also have plausible roles in the expression of ethanol-related behaviors through direct and indirect effects on brain function. The current experiments examined whether insulin administration or the resultant hypoglycemia might attenuate the development of sensitization to the locomotor stimulant effect of ethanol. Main methods Male and female DBA/2J mice received daily injections of 5 or 10 IU/kg insulin before or after a stimulating dose of ethanol and subsequent testing in an automated activity monitor. Blood glucose levels were determined upon the completion of the experiments. Key findings Insulin injected prior to ethanol blunted the acute stimulant response as well as the acquisition and expression of locomotor sensitization, while insulin given after ethanol did not affect the development of the sensitized response. In a separate experiment, mice given glucose concurrently with insulin developed ethanol-induced locomotor sensitization normally. Significance These experiments suggest that insulin attenuates the development of ethanol-induced locomotor sensitization, and that blood glucose levels can largely account for this effect. Further studies of the role of ethanol-induced metabolic states should provide novel information on the expression of ethanol-related behaviors. PMID:22056372

Kliethermes, Christopher L; Heberlein, Ulrike

2011-01-01

113

Seabuckthron (Hippophae rhamnoides L.) leaf extract ameliorates the gamma radiation mediated DNA damage and hepatic alterations.  

PubMed

In vitro assessment showed that H. rhamnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (gamma) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of beta radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkappaB (p65) and IkappaBalpha increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures. PMID:25345244

Khan, Amitava; Manna, Krishnendu; Chinchubose; Das, Dipesh Kr; Sinha, Mahuya; Kesh, Swaraj Bandhu; Das, Ujjal; Dey, Rakhi Sharma; Banerji, Asoke; Dey, Sanjit

2014-10-01

114

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

115

Kupffer cells inhibition prevents hepatic lipid peroxidation and damage induced by carbon tetrachloride  

Microsoft Academic Search

The aim of this work was to determine if the action mechanism of gadolinium on CCl4-induced liver damage is by preventing lipid peroxidation (that may be induced by Kupffer cells) and its effects on liver carbohydrate metabolism. Four groups of rats were treated with CCl4, CCl4+GdCl3, GdCl3, and vehicles. CCl4 was given orally (0.4 g 100 g?1 body wt.) and

Pablo Muriel; Nicolas Alba; Victor M Pérez-Álvarez; Mineko Shibayama; Victor K Tsutsumi

2001-01-01

116

Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain  

PubMed Central

GM2 ganglioside in the brain increased during ethanol-induced acute apoptotic neurodegeneration in 7-day-old mice. A small but a significant increase observed 2 h after ethanol exposure was followed by a marked increase around 24 h. Subcellular fractionation of the brain 24 h after ethanol treatment indicated that GM2 increased in synaptic and non-synaptic mitochondrial fractions as well as in a lysosome-enriched fraction characteristic to the ethanol-exposed brain. Immunohistochemical staining of GM2 in the ethanol-treated brain showed strong punctate staining mainly in activated microglia, in which it partially overlapped with staining for LAMP1, a late endosomal/lysosomal marker. Also, there was weaker neuronal staining, which partially co-localized with complex IV, a mitochondrial marker, and was augmented in cleaved caspase-3-positive neurons. In contrast, the control brain showed only faint and diffuse GM2 staining in neurons. Incubation of isolated brain mitochondria with GM2 in vitro induced cytochrome c release in a manner similar to that of GD3 ganglioside. Because ethanol is known to trigger mitochondria-mediated apoptosis with cytochrome c release and caspase-3 activation in the 7-day–old mouse brain, the GM2 elevation in mitochondria may be relevant to neuroapoptosis. Subsequently, activated microglia accumulated GM2, indicating a close relationship between GM2 and ethanol-induced neurodegeneration. PMID:22372857

Saito, Mitsuo; Chakraborty, Goutam; Shah, Relish; Mao, Rui-Fen; Kumar, Asok; Yang, Dun-Sheng; Dobrenis, Kostantin; Saito, Mariko

2012-01-01

117

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

118

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

119

Protective effect of Quercetin in the Regression of Ethanol-Induced Hepatotoxicity  

PubMed Central

This study examined the protective effects of quercetin on chronic ethanol-induced liver injury. Rats were treated with ethanol at a dose of 4 g/100 g/day for 90 days. After ethanol intoxication, levels of serum amino transferases were significantly elevated. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase was also observed on ethanol administration. Increased amounts of lipid peroxidation products viz. hydroperoxides, conjugated dienes and malodialdehyde were observed on ethanol intoxication. Ethanol administration resulted in significant decrease in liver glutathione content. After 90 days, the control animals were divided into two groups, the control group and the control+quercetin group. Ethanol-treated group was divided into two groups, abstention group and quercetin-supplemented group. After 30 days, the animals were sacrificed and various biochemical parameters were analyzed. The changes in enzyme activities as well as levels of lipid peroxidation products were reversed to a certain extent by quercetin. Quercetin supplementation resulted in increase of glutathione content to a significant level compared to normal abstention group. Quercetin supplemented group showed a faster recovery than abstention group. This shows the protective effect of quercetin against chronic ethanol induced hepatotoxicity. Histopathological study is also in line with these results. PMID:20502571

Vidhya, A.; Indira, M.

2009-01-01

120

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

121

Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.  

PubMed

The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 ?g/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. PMID:23546397

Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

2013-03-28

122

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

123

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

Microsoft Academic Search

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

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

2001-01-01

124

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 (2.5g/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

125

Rutin attenuates ethanol-induced neurotoxicity in hippocampal neuronal cells by increasing aldehyde dehydrogenase 2.  

PubMed

Rutin is derived from buckwheat, apples, and black tea. It has been shown to have beneficial anti-inflammatory and antioxidant effects. Ethanol is a central nervous system depressant and neurotoxin. Its metabolite, acetaldehyde, is critically toxic. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde into nontoxic acetate. This study examined rutin's effects on ALDH2 activity in hippocampal neuronal cells (HT22 cells). Rutin's protective effects against acetaldehyde-based ethanol neurotoxicity were confirmed. Daidzin, an ALDH2 inhibitor, was used to clarify the mechanisms of rutin's protective effects. Cell viability was significantly increased after rutin treatment. Rutin significantly reversed ethanol-increased Bax, cytochrome c expression and caspase 3 activity, and decreased Bcl-2 and Bcl-xL protein expression in HT22 cells. Interestingly, rutin increased ALDH2 expression, while daidzin reversed this beneficial effect. Thus, this study demonstrates rutin protects HT22 cells against ethanol-induced neurotoxicity by increasing ALDH2 activity. PMID:25084483

Song, Kibbeum; Kim, Sokho; Na, Ji-Young; Park, Jong-Heum; Kim, Jae-Kyung; Kim, Jae-Hun; Kwon, Jungkee

2014-10-01

126

Two Case Reports of Life-Threatening Ethanol-Induced Anaphylaxis  

PubMed Central

Adverse reactions to alcoholic beverages are common and diverse in aetiology. Ethanol-induced anaphylaxis, however, is a rare but often life-threatening condition that warrants careful evaluation in suspected individuals. We present the cases of two patients who developed urticaria, angioedema and throat constriction within minutes of consuming white wine. Both individuals demonstrated no adverse reaction to double-blind placebo-controlled challenges to metabisulphite or sodium salicylate. However, an open challenge to white wine elicited urticaria in both subjects. This reaction was reproduced with a double-blind placebo-controlled challenge to ethanol and was accompanied by a rise in serum total tryptase levels. Positive skin test responses to 2% acetic acid, a breakdown product of ethanol, were elicited from both patients but not from three normal controls. These two cases demonstrate the need for a systematic approach for the evaluation of allergic reactions to alcohol. PMID:20508822

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

2009-01-01

127

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

128

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

129

Ethanol-induced delayed male puberty in mice is not due to impaired Leydig cell function.  

PubMed

The present study was performed to evaluate the involvement of reduced testosterone in ethanol-induced impairment of male reproductive tract development. In vivo and in vitro gonadotropin (hCG)-stimulated steroidogenesis were examined in CFW mice as a function of chronic ethanol treatment during pubertal development. Chronic ethanol treatment from ages 20 to 49 days impaired testicular growth from ages 35 days (29 +/- 2 mg vs 37 +/- 2 mg for pair-fed controls) to 50 days (42 +/- 2 mg vs 63 +/- 2 mg for pair-fed controls). Consistent with a reduction in testicular weight, testicular content of androstenedione, testosterone, and dihydrotestosterone (DHT) was depressed in ethanol-treated mice. At age 50 days, the content (expressed as pg/testis) of androstenedione, testosterone, and DHT was reduced in ethanol-treated animals by 49%, 31%, and 38%, respectively, as compared to that of their respective controls. However, no difference in plasma (ng/mL) or testicular (pg/mg protein) concentrations of steroids was observed. Except for the DHT response at ages 35 to 40 days, neither in vivo nor in vitro steroidogenesis was impaired by chronic ethanol treatment at ages 26 to 50 days; similarly, the acute ethanol effect on steroidogenesis was unaffected. However, an adaptive increase (54%-173%) in the in vivo testosterone response to hCG was seen at ages 26 to 40 days. The data indicate that 1) chronic ethanol treatment does not impair gonadotropin-stimulated steroidogenesis or result in tolerance to acute ethanol effects on steroidogenesis in older animals; and 2) ethanol-induced reduction in testosterone is not a likely mechanism for delayed sexual maturation. PMID:2520509

Anderson, R A; Phillips, J F; Berryman, S H; Zaneveld, L J

1989-01-01

130

Ethanol induces oxidative stress in alveolar macrophages via upregulation of NADPH oxidases  

PubMed Central

BACKGROUND Chronic alcohol abuse is a comorbid variable of Acute Respiratory Distress Syndrome (ARDS). Previous studies showed that, in the lung, chronic alcohol consumption increased oxidative stress and impaired alveolar macrophage (AM) function. NADPH oxidases (Nox) are the main source of reactive oxygen species (ROS) in AMs. Therefore, we hypothesized that chronic alcohol consumption increases AM oxidant stress through modulation of Nox1, Nox2 and Nox4 expression. METHODS AMs were isolated from male C57BL/6J mice, aged 8-10 weeks, which were treated ± ethanol in drinking water (20% w/v, 12 weeks). MH-S cells, a mouse AM cell line, were treated ± ethanol (0.08%, 3 days) for in vitro studies. Selected cells were treated with apocynin (300 ?M), a Nox1 and Nox2 complex formation inhibitor, or were transfected with Nox siRNAs (20-35 nM), prior to ethanol exposure. Human AMs were isolated from alcoholic and control patients’ bronchoalveolar lavage fluid. Nox mRNA levels (qRT-PCR), protein levels (western blot and immunostaining), oxidative stress (DCFH-DA and Amplex Red analysis), and phagocytosis (S. aureus internalization) were measured. RESULTS Chronic alcohol increased Nox expression and oxidative stress in mouse AMs in vivo and in vitro. Experiments using apocynin and Nox siRNAs demonstrated that ethanol-induced Nox4 expression, oxidative stress, and AM dysfunction were modulated through Nox1 and Nox2 upregulation. Further, Nox1, Nox2 and Nox4 protein levels were augmented in human AMs from alcoholics compared with controls. CONCLUSIONS Ethanol induces AM oxidative stress initially through upregulation of Nox1 and Nox2 with downstream Nox4 upregulation and subsequent impairment of AM function. PMID:22412195

Yeligar, Samantha M.; Harris, Frank L.; Hart, C. Michael; Brown, Lou Ann S.

2012-01-01

131

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...

132

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....

133

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

Microsoft Academic Search

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

Yu-Kan Liu; Wei Shen

2003-01-01

134

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

135

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

PubMed

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

Prabakaran, Dhamodaran; Ashokkumar, Natarajan

2013-02-01

136

Medium-chain TAG attenuate hepatic oxidative damage in intra-uterine growth-retarded weanling piglets by improving the metabolic efficiency of the glutathione redox cycle.  

PubMed

The present study investigated the effects of medium-chain TAG (MCT) on hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). At weaning (mean 21 (SD 1·06) d of age), twenty-four IUGR piglets and twenty-four normal-birth weight (NBW) piglets were selected according to their birth weight (BW; IUGR: mean 0·95 (SD 0·04) kg; NBW: mean 1·58 (SD 0·04) kg) and weight at the time of weaning (IUGR: mean 5·26 (SD 0·15) kg; NBW: mean 6·98 (SD 0·19) kg) and fed either a soyabean oil (SO) diet (containing 5% SO) or a MCT diet (containing 1% SO and 4% MCT) for 28 d. IUGR piglets exhibited poor (P<0·05) growth performance, lower (P<0·05) metabolic efficiency of hepatic glutathione (GSH) redox cycle, and increased (P<0·05) levels of reactive oxygen species, apoptosis and necrosis in hepatocytes compared with NBW piglets. The MCT diet increased (P<0·05) the average daily gain and feed efficiency of piglets during the first 4 weeks after weaning. Furthermore, MCT diet-fed piglets had a higher (P<0·05) GSH:oxidised glutathione ratio and increased (P<0·05) activities of glucose-6-phosphate dehydrogenase (G6PD) and GSH reductase. The expression of G6PD was up-regulated (P<0·05) by the MCT diet irrespective of BW. Moreover, malondialdehyde concentrations in the liver and apoptosis and necrosis levels in hepatocytes were decreased (P<0·05) by the MCT diet irrespective of BW. These results indicate that MCT might have auxiliary therapeutic potential to attenuate hepatic oxidative damage in IUGR offspring during early life, thus leading to an improvement in the metabolic efficiency of the hepatic GSH redox cycle. PMID:25083907

Zhang, Hao; Chen, Yueping; Li, Yue; Yang, Li; Wang, Jianjun; Wang, Tian

2014-09-28

137

Polo-like Kinase 1 Activated by the Hepatitis B Virus X Protein Attenuates Both the DNA Damage Checkpoint and DNA Repair Resulting in Partial Polyploidy*  

PubMed Central

Hepatitis B virus X protein (pX), implicated in hepatocarcinogenesis, induces DNA damage because of re-replication and allows propagation of damaged DNA, resulting in partial polyploidy and oncogenic transformation. The mechanism by which pX allows cells with DNA damage to continue proliferating is unknown. Herein, we show pX activates Polo-like kinase 1 (Plk1) in the G2 phase, thereby attenuating the DNA damage checkpoint. Specifically, in the G2 phase of pX-expressing cells, the checkpoint kinase Chk1 was inactive despite DNA damage, and protein levels of claspin, an adaptor of ataxia telangiectasia-mutated and Rad3-related protein-mediated Chk1 phosphorylation, were reduced. Pharmacologic inhibition or knockdown of Plk1 restored claspin protein levels, Chk1 activation, and p53 stabilization. Also, protein levels of DNA repair protein Mre11 were decreased in the G2 phase of pX-expressing cells but not with Plk1 knockdown. Interestingly, in pX-expressing cells, Mre11 co-immunoprecipitated with transfected Plk1 Polo-box domain, and inhibition of Plk1 increased Mre11 stability in cycloheximide-treated cells. These results suggest that pX-activated Plk1 by down-regulating Mre11 attenuates DNA repair. Importantly, concurrent inhibition of Plk1, p53, and Mre11 increased the number of pX-expressing cells with DNA damage entering mitosis, relative to Plk1 inhibition alone. By contrast, inhibition or knockdown of Plk1 reduced pX-induced polyploidy while increasing apoptosis. We conclude Plk1, activated by pX, allows propagation of DNA damage by concurrently attenuating the DNA damage checkpoint and DNA repair, resulting in polyploidy. We propose this novel Plk1 mechanism initiates pX-mediated hepatocyte transformation. PMID:20624918

Studach, Leo; Wang, Wen-Horng; Weber, Gregory; Tang, Jiabin; Hullinger, Ronald L.; Malbrue, Raphael; Liu, Xiaoqi; Andrisani, Ourania

2010-01-01

138

Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells.  

PubMed

Earlier studies from this and other laboratories show that ethanol induces apoptotic death of fetal and neonatal neurons. One mechanism that underlies these effects is the ethanol-associated reduction in the phosphatidylinositol 3' kinase pro-survival pathway. Another mechanism involves the oxidative stress caused by the ethanol-associated increase in reactive oxygen species (ROS). In the present study, we used the murine HN2-5 hippocampal-derived cell line to investigate the effects of ethanol on ROS levels and apoptosis. We also investigated the potential neuroprotective effects of two structurally unrelated antioxidants: N-acetylcysteine (NAC) and melatonin. The results demonstrate that NAC blocked an ethanol-associated increase in ROS. In addition, NAC and melatonin prevented the augmentation of apoptosis in ethanol-treated neurons. Both antioxidants significantly elevated the expression of the anti-apoptotic gene XIAP in ethanol-treated and/or control neurons and melatonin increased Bcl-2 expression in ethanol-treated neurons. Thus, it is possible that the neuroprotective effects of NAC and melatonin involve their ability to augment the expression of one or more anti-apoptotic gene as well as their classical antioxidant actions. Additional studies are needed to establish the effectiveness of these antioxidants to prevent the loss of neurons which accompanies in utero exposure to ethanol. PMID:19538946

Sheth, Dhara S; Tajuddin, Nuzhath F; Druse, Mary J

2009-08-18

139

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

PubMed Central

Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ?30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl? from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl? and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms. PMID:25033198

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

2014-01-01

140

Effects of a Drd2 Deletion Mutation on Ethanol-Induced Locomotor Stimulation and Sensitization Suggest a Role for Epistasis  

Microsoft Academic Search

Interpretation of studies using single gene mutants is complicated by possible epistatic interactions with genetic background. Dopamine D2 receptor (Drd2) knockout mice on a C57BL\\/6 (B6) background show decreased basal locomotion, ethanol preference and ethanol-induced ataxia. Epistatic interactions were studied by examining the effect of this null mutation on several traits on a B6 or 129S6 × 129S2 (129) background.

Abraham A. Palmer; Malcolm J. Low; David K. Grandy; Tamara J. Phillips

2003-01-01

141

Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.  

PubMed

The production of reactive oxygen species (ROS) is considered to be a major factor in oxidative cell injury. The antioxidant activity or the inhibition of the generation of free radicals is important in providing protection against such hepatic damage. Silymarin, derived from the milk thistle plant, Silybium marianum, has been used in traditional medicine as a remedy for diseases of the liver and biliary tract. In the present study, the effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Ethanol, at a dose of 1.6 g/kg body wt/day for 4 wks affected body weight in 16-18 week-old male albino rats (Wistar strain weighing 200-220 g). Thiobarbituric acid reactive substance (TBARS) level, superoxide dismutase (SOD), and glutathione-s-transferase (GST) activities were significantly increased, whereas GSH content, and catalase, glutathione reductase (GR) and GPx (glutathione peroxidase) activities significantly reduced, on ethanol exposure. These changes were reversed by silybin and ascorbic acid treatment. It was also observed that abstinence from ethanol might help in hepatic regeneration. Silybin showed a significant hepatoprotective activity, but activity was less than that of ascorbic acid. Furthermore, preventive measures were more effective than curative treatment. PMID:17133738

Das, Subir Kumar; Vasudevan, D M

2006-10-01

142

Involvement of tissue plasminogen activator "tPA" in ethanol-induced locomotor sensitization and conditioned-place preference.  

PubMed

Ethanol is one of the most abused drugs in the western societies. It is well established that mesolimbic dopaminergic neurons mediate the rewarding properties of ethanol. In our previous studies we have shown that the serine protease tissue plasminogen activator (tPA) is involved in the rewarding properties of morphine and amphetamine. In the current study, we investigated the role of tPA in ethanol-induced behavioral sensitization and conditioned-place preference (CPP). Ethanol treatment dose-dependently induced tPA enzymatic activity in the nucleus accumbens (NAc). In addition, ethanol-induced increase in tPA activity was completely inhibited by pre-treatment with the dopamine D1 and D2 receptor antagonists SCH23390 and raclopride respectively. Furthermore, ethanol-induced locomotor stimulation, behavioral sensitization and conditioned-place preference were enhanced following tPA over-expression in the NAc using a lentiviral vector. In contrast, tPA knock down in the NAc with specific shRNA blocked the rewarding properties of ethanol. The defect of locomotor stimulation in shRNA-injected mice was reversed by microinjections of exogenous recombinant tPA into the nucleus accumbens. Collectively, these results indicate, for the first time, that activation of tPA is effective in enhancing the rewarding effects of ethanol. Targeting the tissue plasminogen activator system would provide new therapeutic approaches to the treatment of alcoholism. PMID:21945298

Bahi, Amine; Dreyer, Jean-Luc

2012-01-01

143

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

PubMed

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

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

2005-08-22

144

Oxidative stress mediated toxicity exerted by ethanol-inducible CYP2E1  

SciTech Connect

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

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

2005-09-01

145

Ethanol induced mitochondria injury and permeability transition pore opening: Role of mitochondria in alcoholic liver disease  

PubMed Central

AIM: To observe changes of mitochondria and investigate the effect of ethanol on mitochondrial perme-ability transition pore (PTP), mitochondrial membrane potential (MMP, ??m) and intracellular calcium concentration in hepatocytes by establishing an animal model of alcoholic liver disease (ALD). METHODS: Fourty adult male Wistar rats were randomly divided into two groups, the model group (20) was administered alcohol intragastrically plus an Oliver oil diet to establish an ALD model, and the control group (20) was given an equal amount of normal saline. The ultramicrostructural changes of mitochondria were observed under electron microscopy. Mitochondria of liver was extracted, and patency of PTP, mitochondrial membrane potential (??m), mitochondrial mass and intracellular calcium concentration of isolated hepacytes were detected by flow cytometry using rhodamine123 (Rh123), Nonyl-Acridine Orange and calcium fluorescent probe Fluo-3/AM, respectively. RESULTS: Membrane and cristae were broken or disappeared in mitochondria in different shapes under electron microscopy. Some mitochondria showed U shape or megamitochondrion. In the model group, liver mitochondria PTP was broken, and mitochondria swelled, the absorbance at 450 nm, A540 decreased (0.0136 ± 0.0025 vs 0.0321 ± 0.0013, model vs control, P < 0.01); mitochondria transmembrane potential (239.4638 ±12.7263 vs 377.5850 ± 16.8119, P < 0.01) was lowered; mitochondrial mass (17.4350 ± 1.9880 vs 31.6738 ± 3.4930, P < 0.01); and [Ca2+]i was increased in liver cells (7.0020 ± 0.5008 vs 10.2050 ± 0.4701, P < 0.01). CONCLUSION: Chronic alcohol intake might lead to broken mitochondria PTP, decreased mitochondria membrane potential and injury, and elevated intracellular Ca2+ production. Ethanol-induced chondriosome injury may be an important mechanism of alcoholic diseases. PMID:17511037

Yan, Ming; Zhu, Ping; Liu, Hui-Min; Zhang, Hai-Tao; Liu, Li

2007-01-01

146

Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis.  

PubMed

The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin. PMID:17484288

Kaviarasan, S; Anuradha, C V

2007-04-01

147

Ethanol-Induced Microphthalmia is Not Mediated by Changes in Retinoic Acid or Sonic Hedgehog Signaling During Retinal Neurogenesis  

PubMed Central

Background Microphthalmia (reduced eye size), generally accompanied by vision defects, is a hallmark of fetal alcohol spectrum disorder (FASD) in humans. In zebrafish, embryonic ethanol exposure over the time of retinal neurogenesis also results in microphthalmia. This microphthalmia is in part the consequence of reduced retinal cell differentiation, including photoreceptors. Here we pursue 2 signaling pathways implicated in other aspects of FASD pathogenesis: retinoic acid (RA) and Sonic hedgehog (Shh). Methods We evaluated markers for RA and Shh signaling within the eyes of embryos treated with ethanol during the period of retinal neurogenesis. We also perrormed rescue experiments using administration of exogenous RA and microinjection of cholesterol, which augments Shh signaling. Results Using sequential or co-treatments, RA did not rescue ethanol-induced microphthalmia at any concentration tested. In addition, RA itself caused microphthalmia, although the underlying mechanisms were distinct from those or ethanol. Interestingly, RA treatment appeared to recover photoreceptor differentiation in a concentration-dependent manner. This may be an independent effect or exogenous RA, as ethanol treatment alone did not alter RA signaling in the eye. Cholesterol injection also did not rescue ethanol-induced microphthalmia at any concentration tested, and ethanol treatments did not alter expression of shh, or of ptc-2, which is normally regulated by Shh signaling. Conclusions Together these findings indicate that, during the time of retinal neurogenesis, effects of ethanol on eye development are likely independent of the RA and Shh signaling pathways. These studies suggest that FASD intervention strategies based upon augmentation or RA or Shh signaling may not prevent ethanol-induced microphthalmia. PMID:21554333

Kashyap, Bhavani; Frey, Ruth A.; Stenkamp, Deborah L.

2012-01-01

148

Depletion of activated hepatic stellate cell correlates with severe liver damage and abnormal liver regeneration in acetaminophen-induced liver injury.  

PubMed

Hepatic stellate cells (HSCs) are important part of the local 'stem cell niche' for hepatic progenitor cells (HPCs) and hepatocytes. However, it is unclear as to whether the products of activated HSCs are required to attenuate hepatocyte injury, enhance liver regeneration, or both. In this study, we performed 'loss of function' studies by depleting activated HSCs with gliotoxin. It was demonstrated that a significantly severe liver damage and declined survival rate were correlated with depletion of activated HSCs. Furthermore, diminishing HSC activation resulted in a 3-fold increase in hepatocyte apoptosis and a 66% decrease in the number of proliferating hepatocytes. This was accompanied by a dramatic decrease in the expression levels of five genes known to be up-regulated during hepatocyte replication. In particular, it was found that depletion of activated HSCs inhibited oval cell reaction that was confirmed by decreased numbers of Pank-positive cells around the portal tracts and lowered gene expression level of cytokeratin 19 (CK19) in gliotoxin-treated liver. These data provide clear evidence that the activated HSCs are involved in both hepatocyte death and proliferation of hepatocytes and HPCs in acetaminophen (APAP)-induced acute liver injury. PMID:21335335

Shen, Kuntang; Chang, Wenju; Gao, Xiaodong; Wang, Hongshan; Niu, Weixin; Song, Lujun; Qin, Xinyu

2011-04-01

149

AIM2 Mediates Inflammation-Associated Renal Damage in Hepatitis B Virus-Associated Glomerulonephritis by Regulating Caspase-1, IL-1?, and IL-18  

PubMed Central

Background & Aims. AIM2 plays an important role in innate immunity, but its role in regulating the immune response to hepatitis B virus (HBV) is unknown. We hypothesized that AIM2 expression is positively correlated with HBV-mediated inflammation in patients with HBV-associated glomerulonephritis (HBV-GN), potentiating inflammation and leading to renal damage. We therefore analyzed the expression of AIM2 and inflammatory factors in HBV-GN tissues and cell lines relative to the inflammatory response to HBV infection and HBV status. Methods. Seventy-nine patients with chronic nephritis (CN) were included: 54 with HBV-GN and 24 with chronic glomerulonephritis (CGN). Expression of AIM2, caspase-1, and IL-1? was detected by immunohistochemistry in renal biopsies from each patient. Following siRNA-mediated knockdown of AIM2 in HBV-infected and HBV-uninfected human glomerular mesangial (HGM) cells, expression of caspase-1, IL-1?, and IL-18 was detected by qRT-PCR and Western blot. Results. AIM2 expression in HBV-GN biopsies (81.4%) was significantly higher than in CGN (4.0%) and positively correlated with caspase-1 and IL-1? expression in HBV-GN. In vitro, AIM2 knockdown reduced caspase-1, IL-1?, and IL-18 expression in HBV-infected and HBV-uninfected HGM cells. Conclusion. AIM2 elevation during HBV infection or replication may contribute to inflammatory damage, thus providing a putative therapeutic target for HBV-GN. PMID:24701032

Zhen, Junhui; Zhang, Le; Pan, Jiachao; Ma, Shumin; Yu, Xiaojian; Li, Xiaobo; Chen, Shijun; Du, Wenjun

2014-01-01

150

Hepatoprotective effect of the aqueous extract of Simarouba amara Aublet (Simaroubaceae) stem bark against carbon tetrachloride (CCl4)-induced hepatic damage in rats.  

PubMed

Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle-corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver. PMID:25365298

Maranhão, Hélida M L; Vasconcelos, Carlos F B; Rolim, Larissa A; Neto, Pedro J Rolim; Neto, Jacinto da C Silva; Filho, Reginaldo C da Silva; Fernandes, Mariana P; Costa-Silva, João H; Araújo, Alice V; Wanderley, Almir G

2014-01-01

151

Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage: relevance to cancer reduction.  

PubMed

Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl(3) (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe(3+) was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe(3+) was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe(3+)-induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis. PMID:11255233

Karbownik, M; Reiter, R J; Garcia, J J; Cabrera, J; Burkhardt, S; Osuna, C; Lewi?ski, A

2001-01-01

152

Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases  

Microsoft Academic Search

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

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

2003-01-01

153

Zonal differences in ethanol-induced impairments in receptor-mediated endocytosis of asialoglycoproteins in isolated rat hepatocytes  

SciTech Connect

We have shown previously that ethanol-induced defects in receptor-mediated endocytosis of asialoorosomucoid occurred as early as 1 wk after ethanol feeding. This study was undertaken as an initial attempt to establish a possible role of defective receptor-mediated endocytosis in liver injury by investigating whether differences exist in the effects of ethanol on receptor-mediated endocytosis in hepatocytes isolated from different regions of the liver. Perivenule cells, present in the distal half of the liver, are thought to be more susceptible to ethanol-induced liver injury than are the periportal cells located in the proximal half of the liver acini. For these studies, we fed male Sprague-Dawley rats for 7 days with liquid diets containing either ethanol (36% of calories) or isocaloric carbohydrate. Perivenule and periportal hepatocytes were then isolated using a digitonin-collagenase perfusion method. In control animals, cells isolated from the perivenule region bound significantly more ligand than did cells from the periportal region. Amounts of ligand internalized and degraded were also greater in perivenule than in periportal cells in these animals. After ethanol feeding, cells isolated from both the perivenule and periportal regions bound significantly less ligand than their respective controls. This impairment in surface and total binding was more pronounced in perivenule than in periportal cells. Internalization and degradation of the ligand were also more adversely affected in the centrilobular region as shown by decreases of greater than 60% in perivenule cells and by only 20% to 30% in periportal cells of ethanol-fed animals compared with controls.

Casey, C.A.; Kragskow, S.L.; Sorrell, M.F.; Tuma, D.J. (Department of Veterans Affairs Medical Center, Omaha, NE (USA))

1991-02-01

154

Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways  

PubMed Central

As we previously demonstrated in human hepatocellular carcinoma (HepG2) cells, ethanol at low concentration triggers the Fas apoptotic pathway. However, its role in other intracellular signaling pathways remains unknown. Therefore, the aim of the present study was to evaluate the role of low concentration of ethanol on different intracellular signaling pathways. For this purpose, HepG2 cells were treated with 1 mM ethanol for 10 min and the phosphorylation state of protein kinases was determined. In addition, the mRNA levels of transcription factors and genes associated with the Fas apoptotic pathway were determined. Our data demonstrated that ethanol-induced phosphorylation of protein kinases modulates both anti-apoptotic and pro-apoptotic mechanisms in HepG2 cells. Pro-apoptosis resulted mainly from the strong inhibition of the G-protein couple receptor signaling pathway. Moreover, the signal transduction initiated by ethanol-induced protein kinases phosphorylation lead to increased expression of the transcription factors with subsequent expression of genes associated with the Fas apoptotic pathway (Fas receptor, Fas ligand, FADD and caspase 8). These results indicate that low concentration of ethanol exert their effect by predominant activation of pro-apoptotic events that can be divided in two phases. An early phase characterized by a rapid transient effect on protein kinases phosphorylation, after 10 min exposure, with subsequent increased expression of transcription factors for up to 6 hr. This early phase is followed by a second phase associated with increased gene expression that began after 6 hr and persisted for more than 24 hr. This information provided a novel insight into the mechanisms of action of ethanol (1mM) in human hepatocellular carcinoma cells. PMID:17088943

Castaneda, Francisco; Rosin-Steiner, Sigrid

2006-01-01

155

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

156

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

157

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...

158

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...

159

Autophagy in Hepatic Fibrosis  

PubMed Central

Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future. PMID:24779010

Zhao, Yingying; Wang, Fei; Tao, Lichan; Yang, Changqing

2014-01-01

160

The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats.  

PubMed

This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl4 administration. Pretreatment with DADS attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-?B) and phosphorylation of I kappaB alpha (I?B?) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, DADS inhibited NF-?B translocation and I?B? phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, DADS prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that DADS increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury. These findings indicate that DADS induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-?B activation. PMID:24246655

Lee, In-Chul; Kim, Sung-Hwan; Baek, Hyung-Seon; Moon, Changjong; Kang, Seong-Soo; Kim, Sung-Ho; Kim, Yun-Bae; Shin, In-Sik; Kim, Jong-Choon

2014-01-01

161

Administration of eliprodil during ethanol withdrawal in the neonatal rat attenuates ethanol-induced learning deficits  

Microsoft Academic Search

Rationale Prenatal exposure to alcohol can disrupt brain development, leading to a variety of behavioral alterations, including learning deficits. We have postulated that some central nervous system damage may be due to N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity that occurs during ethanol withdrawal. Consistent with this hypothesis, we previously demonstrated that administration of MK-801, an NMDA receptor antagonist, during ethanol withdrawal attenuates

J. D. Thomas; G. G. Garcia; H. D. Dominguez; E. P. Riley

2004-01-01

162

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

PubMed Central

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

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

2011-01-01

163

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

PubMed Central

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

2013-01-01

164

Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal Cells-PC12.  

PubMed

Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral changes are well documented. Experimental evidences suggest that ethanol could enhance the absorption of metals in the body, and alcohol consumption may increase the susceptibility to metal intoxication in the brain. However, the underlying mechanism of ethanol action in affecting metal toxicity in brain cells is poorly understood. Thus, an attempt was made to investigate the modulatory effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells were co-exposed to biological safe doses of Pb (10 ?M) and ethanol (200 mM), and data were compared to the response of cells which received independent exposure to these chemicals at similar doses. Ethanol (200 mM) exposure significantly aggravated the Pb-induced alterations in the end points associated with oxidative stress and apoptosis. The finding confirms the involvement of reactive oxygen species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane potential, which subsequently facilitate the translocation of triggering proteins between cytoplasm and mitochondria. We further confirmed the apoptotic changes due to induction of mitochondria-mediated caspase cascade. These cellular changes were found to recover significantly, if the cells are exposed to N-acetyl cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate Pb-induced cellular damage in brain cells, but such damaging effects could be recovered by inhibition of ROS generation. These results open up further possibilities for the design of new therapeutics based on antioxidants to prevent neurodegeneration and associated health problems. PMID:25367877

Kumar, V; Tripathi, V K; Jahan, S; Agrawal, M; Pandey, A; Khanna, V K; Pant, A B

2014-11-01

165

Nitric oxide mediated intestinal injury is required for alcohol-induced gut leakiness and liver damage  

PubMed Central

Background Alcoholic liver disease (ALD) requires endotoxemia and is commonly associated with intestinal barrier leakiness. Using monolayers of intestinal epithelial cells as an in vitro barrier model, we showed that ethanol-induced intestinal barrier disruption is mediated by iNOS (inducible nitric-oxide synthase) upregulation, NO (nitric oxide) overproduction, and oxidation/nitration of cytoskeletal proteins. We hypothesized that iNOS inhibitors (L-NAME, L-NIL) in vivo will inhibit the above cascade and liver injury in an animal model of alcoholic steatohepatitis (ASH). Methods Male Sprague-Dawley rats were gavaged daily with alcohol (6 g/kg/day) or dextrose for 10 weeks ± L-NAME, L-NIL or vehicle. Systemic and intestinal NO levels were measured by nitrites and nitrates in urine and tissue samples, oxidative damage to the intestinal mucosa by protein carbonyl and nitrotyrosine, intestinal permeability by urinary sugar tests, and liver injury by histological inflammation scores, liver fat, and myeloperoxidase activity. Results Alcohol caused tissue oxidation, gut leakiness, endotoxemia and ASH. L-NIL and L-NAME, but not the D-enantiomers, attenuated all steps in the alcohol-induced cascade including NO overproduction, oxidative tissue damage, gut leakiness, endotoxemia, hepatic inflammation and liver injury. Conclusions The mechanism we reported for alcohol-induced intestinal barrier disruption in vitro – NO overproduction, oxidative tissue damage, leaky gut, endotoxemia and liver injury – appears to be relevant in vivo in an animal model of alcohol-induced liver injury. That iNOS inhibitors attenuated all steps of this cascade suggests that prevention of this cascade in alcoholics will protect the liver against the injurious effects of chronic alcohol and that iNOS may be a useful target for prevention of ALD. PMID:19389191

Tang, Yueming; Forsyth, Christopher B.; Farhadi, Ashkan; Rangan, Jayanthi; Jakate, Shriram; Shaikh, Maliha; Banan, Ali; Fields, Jeremy Z.; Keshavarzian, Ali

2010-01-01

166

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

PubMed

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

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

2013-09-01

167

Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity.  

PubMed

Non-synonymous single nucleotide polymorphisms (nsSNPs) that cause amino acid changes are believed to have a large impact on protein function. It is important to distinguish those deleterious nsSNPs that affect protein function from those that are functionally neutral. Ethanol causes organ toxicity with involvement of a number of genes encoding functional proteins. We have identified 1509 alcohol-responsive genes after a systemic search of previous human studies, with 580 being up-regulated and 847 down-regulated. The samples for gene expression analysis of ethanol exposure are from the brain, liver, and cultured human cells. These genes mainly encode proteins involved in nucleic acid binding, transcription, and signal transduction. These ethanol-responsive genes also correlated with other biological pathways, such as angiogenesis, integrin signalling pathway, and inflammation. The number of nsSNPs in the 1509 validated alcohol-responsive genes was 9207. Using the PolyPhen and SIFT algorithms, 41.5% nsSNPs were predicted to be deleterious. These findings provide some insights into the molecular targets of ethanol-induced toxicity and how genetic mutation would affect the toxicity phenotype. A better understanding of the relationship between genotype and phenotype of nsSNPs of ethanol-responsive genes will provide useful hints for further research on alcohol-induced toxicity and potential therapy. PMID:19429251

Wang, Lin-Lin; Li, Yong; Zhou, Shu-Feng

2009-06-01

168

Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.  

PubMed

Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders. PMID:23194312

Bahi, Amine

2013-07-01

169

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

PubMed

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

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

2013-01-01

170

Changes in CREB activation in the prefrontal cortex and hippocampus blunt ethanol-induced behavioral sensitization in adolescent mice  

PubMed Central

Drug dependence is a major health problem in adults and has been recognized as a significant problem in adolescents. We previously demonstrated that repeated treatment with a behaviorally sensitizing dose of ethanol in adult mice induced tolerance or no sensitization in adolescents and that repeated ethanol-treated adolescents expressed lower Fos and Egr-1 expression than adult mice in the prefrontal cortex (PFC). In the present work, we investigated the effects of acute and repeated ethanol administration on cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) DNA-binding activity using the electrophoretic mobility shift assay (EMSA) and the phosphorylated CREB (pCREB)/CREB ratio using immunoblotting in both the PFC and hippocampus in adolescent and adult mice. Adult mice exhibited typical locomotor sensitization after 15 days of daily treatment with 2.0 g/kg ethanol, whereas adolescent mice did not exhibit sensitization. Overall, adolescent mice displayed lower CREB binding activity in the PFC compared with adult mice, whereas opposite effects were observed in the hippocampus. The present results indicate that ethanol exposure induces significant and differential neuroadaptive changes in CREB DNA-binding activity in the PFC and hippocampus in adolescent mice compared with adult mice. These differential molecular changes may contribute to the blunted ethanol-induced behavioral sensitization observed in adolescent mice. PMID:24379765

Soares-Simi, Sabrina L.; Pastrello, Daniel M.; Ferreira, Zulma S.; Yonamine, Mauricio; Marcourakis, Tania; Scavone, Cristoforo; Camarini, Rosana

2013-01-01

171

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

172

Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.  

PubMed

Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward. PMID:23601049

Bahi, Amine; Dreyer, Jean-Luc

2013-07-01

173

Alcoholic hepatitis and concomitant hepatitis C virus infection  

PubMed Central

Hepatitis C virus (HCV) infection and alcohol abuse are two most important causes of chronic liver disease in the United States. Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality. About 20% of patients presenting with alcoholic hepatitis have concomitant HCV infection. Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage. Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection. The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research. PMID:25232227

Shoreibah, Mohamed; Anand, Bhupinderjit S; Singal, Ashwani K

2014-01-01

174

Diminution of ethanol-induced hyperglycaemia in the rat by administration of beta-lactam antibiotics with a tetrazole thiol group.  

PubMed

The acute-onset hyperglycaemia produced by i.p. injection of 2 g of ethanol/kg body weight in adult female SPF Sprague-Dawley rats (200-220 g) was considerably less pronounced when 100 mumol/kg b.w. of one of the following tetrazole thiol-containing beta-lactam antibiotics (BLAs) was given i.p. 3 hours in advance: cephamandole (CMD), moxalactam (MOX), cephoperazone (CPZ) or cephothiam (CTM). An equimolar dose of cephazolin (CEZ), a thiadiazole thiol-containing cephalosporin, did not affect the ethanol-induced hyperglycaemia. Administration of an equimolar oral dose of disulfiram, which has an NCS structure similar to that of the tetrazole thiol-containing BLAs, produced an additional increase of the ethanol-induced hyperglycaemia. The diminution of the ethanol-induced hyperglycaemia by BLAs with a tetrazole thiol group appears to be linked to their NCS structure. It is conceivable that this effect which might be important for human therapy, is causally related to an inhibition of the glycolytic or gluconeogenetic enzyme system. PMID:6889426

Römer, K G; Alanis, O T; de Torres, G G; Freundt, K J

1983-06-01

175

Hepatitis B  

MedlinePLUS

... of the liver due to infection with the hepatitis B virus (HBV). Other types of viral hepatitis include: Hepatitis ... Hepatitis B infection is caused by the hepatitis B virus (HBV).You ... or body fluids (such as semen, vaginal fluids, and saliva) of a ...

176

Hepatitis B  

MedlinePLUS

... is a serious liver infection caused by the hepatitis B virus. The virus is usually spread from person to ... Hepatitis B is caused by infection with the hepatitis B virus. You can get the virus if you have ...

177

Hepatitis C Virus Infection Activates the Immunologic (Type II) Isoform of Nitric Oxide Synthase and Thereby Enhances DNA Damage and Mutations of Cellular Genes  

Microsoft Academic Search

Hepatitis C virus (HCV) infection causes hepatitis, hepatocellular carcinoma, and B-cell lymphomas in a significant number of patients. Previously we have shown that HCV infection causes double-stranded DNA breaks and enhances the mutation frequency of cellular genes, including proto-oncogenes and immunoglobulin genes. To determine the mechanisms, we studied in vitro HCV infection of cell culture. Here we report that HCV

Keigo Machida; Kevin T.-H. Cheng; Vicky M.-H. Sung; Ki Jeong Lee; Alexandra M. Levine; Michael M. C. Lai

2004-01-01

178

Dantrolene blockade of ryanodine receptor impairs ethanol-induced behavioral stimulation, ethanol intake and loss of righting reflex.  

PubMed

Calcium has been characterized as one of the most ubiquitous, universal and versatile intracellular signals. Among other substances with the ability to alter intracellular calcium levels, ethanol has been described as particularly relevant because of its social and economic impact. Ethanol effects on calcium distribution and flux in vitro have been widely studied, showing that acute ethanol administration can modulate intracellular calcium concentrations in a dose dependent manner. Intracellular calcium released from the endoplasmic reticulum plays a determinant role in several cellular processes. In this study, we aim to assess the effect of dantrolene, a ryanodine receptor antagonist, on three different ethanol-elicited behaviors: locomotor activity, loss of righting reflex and ethanol intake. Mice were challenged with an injection of dantrolene (0-5 mg/kg, i.p.) 30 min before ethanol (0-4 g/kg, i.p.) administration. Animals were immediately placed in an open field cylinder to monitor distance travelled horizontally or in a V-shaped trough to measure righting reflex recovery time. For ethanol intake, dantrolene (0-5mg/kg, i.p.) was administered 30 min before ethanol (20%, v/v) exposure, following a drinking in the dark paradigm. Our results showed that dantrolene selectively reduces ethanol-induced stimulation, loss of righting reflex, and ethanol intake in a dose dependent manner. Together, these data suggest that intracellular calcium released from the endoplasmic reticulum may play a critical role in behavioral effects caused by ethanol, and point to a calcium-dependent pathway as a possible cellular mechanism of action for ethanol. PMID:22677274

Tarragon, Ernesto; Baliño, Pablo; Aragon, Carlos M G

2012-08-01

179

Presynaptic BK channels modulate ethanol-induced enhancement of GABAergic transmission in the rat central amygdala nucleus.  

PubMed

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; Moore, Scott D

2014-10-01

180

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

PubMed Central

The transient exposure of immature rodents to ethanol during postnatal day 7 (P7), which is comparable to the third trimester human pregnancy, induces synaptic dysfunctions. However, the molecular mechanisms underlying these dysfunctions are still poorly understood. Although the endocannabinoid system has been shown to be an important modulator of ethanol sensitivity in adult mice, its potential role in synaptic dysfunctions in mice exposed to ethanol during early brain development is not examined. In this study, we investigated the potential role of endocannabinoids and the cannabinoid receptor type 1 (CB1R) in neonatal neurodegeneration and adult synaptic dysfunctions in mice exposed to ethanol at P7. Ethanol treatment at P7, which induces neurodegeneration, increased anandamide (AEA) but not 2-arachidonylglycerol biosynthesis and CB1R protein expression in the hippocampus and cortex, two brain areas that are important for memory formation and storage, respectively. N-arachidonoyl phosphatidylethanolamine-phospholipase D (NAPE-PLD), glycerophosphodiesterase (GDE1) and CB1Rs protein expression were enhanced by transcriptional activation of the genes encoding NAPE-PLD, GDE1 and CB1R proteins respectively. In addition, ethanol inhibited ERK1/2 and AKT phosphorylation. The blockade of CB1Rs prior to ethanol treatment at P7 relieved ERK1/2 but not AKT phosphorylation and prevented neurodegeneration. CB1R knockout mice exhibited no ethanol-induced neurodegeneration and inhibition of ERK1/2-phosphorylation. The protective effects of CB1R blockade through pharmacological or genetic deletion resulted in normal adult synaptic plasticity and novel object recognition memory in mice exposed to ethanol at P7. The AEA/CB1R/pERK1/2 signaling pathway may be directly responsible for the synaptic and memory deficits associated with fetal alcohol spectrum disorders. PMID:23575834

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

2013-01-01

181

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

182

Sexual transmission of viral hepatitis.  

PubMed

Identification and vaccination of adults at risk for hepatitis B virus acquisition through sexual contact is a key strategy to reduce new hepatitis B virus infections among at-risk adults. Hepatitis C has emerged as a sexually transmitted infection among men with male sex partners (MSM). Several biological and behavioral factors have been linked to hepatitis C virus transmission among MSM, including human immunodeficiency virus coinfection; participation in sexual practices that result in mucosal damage or result in exposure to blood; presence of sexually transmitted diseases (STIs), particularly ulcerative STIs; multiple/casual sex partners; and unprotected anal intercourse. PMID:24275272

Gorgos, Linda

2013-12-01

183

Protective action of fenugreek ( Trigonella foenum graecum ) seed polyphenols against alcohol-induced protein and lipid damage in rat liver  

Microsoft Academic Search

The study investigates the effect of fenugreek seed polyphenol extract (FPEt) on ethanol-induced damage in rat liver. Chronic\\u000a ethanol administration (6 g kg?1 day?1?×?60 days) caused liver damage that was manifested by excessive formation of thiobarbituric-acid-reactive substances, lipid\\u000a hydroperoxides, and conjugated dienes, the end products of lipid peroxidation, and significant elevation of protein carbonyl\\u000a groups and diminution of sulfhydryl groups, a marker

S. Kaviarasan; R. Sundarapandiyan; C. V. Anuradha

2008-01-01

184

Protective action of fenugreek ( Trigonella foenum graecum ) seed polyphenols against alcohol-induced protein and lipid damage in rat liver  

Microsoft Academic Search

The study investigates the effect of fenugreek seed polyphenol extract (FPEt) on ethanol-induced damage in rat liver. Chronic\\u000a ethanol administration (6 g kg?1 day?1?×?60 days) caused liver damage that was manifested by excessive formation of thiobarbituric-acid-reactive substances, lipid\\u000a hydroperoxides, and conjugated dienes, the end products of lipid peroxidation, and significant elevation of protein carbonyl\\u000a groups and diminution of sulfhydryl groups, a marker

S. Kaviarasan; R. Sundarapandiyan; C. V. Anuradha

185

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

186

Hepatitis B and Hepatitis C in Pregnancy  

MedlinePLUS

... sometimes causes no signs or symptoms. How is hepatitis B virus infection spread? Hepatitis B virus is spread by ... and hepatitis C infections during pregnancy? • How is hepatitis B virus infection spread? • What is acute hepatitis B virus ...

187

Pre-administration of G9a/GLP inhibitor during synaptogenesis prevents postnatal ethanol-induced LTP deficits and neurobehavioral abnormalities in adult mice.  

PubMed

It has been widely accepted that deficits in neuronal plasticity underlie the cognitive abnormalities observed in fetal alcohol spectrum disorder (FASD). Exposure of rodents to acute ethanol on postnatal day 7 (P7), which is equivalent to the third trimester of fetal development in human, induces long-term potentiation (LTP) and memory deficits in adult animals. However, the molecular mechanisms underlying these deficits are not well understood. Recently, we found that histone H3 dimethylation (H3K9me2), which is mediated by G9a (lysine dimethyltransferase), is responsible for the neurodegeneration caused by ethanol exposure in P7 mice. In addition, pharmacological inhibition of G9a prior to ethanol treatment at P7 normalized H3K9me2 proteins to basal levels and prevented neurodegeneration in neonatal mice. Here, we tested the hypothesis that pre-administration of G9a/GLP inhibitor (Bix-01294, Bix) in conditions in which ethanol induces neurodegeneration would be neuroprotective against P7 ethanol-induced deficits in LTP, memory and social recognition behavior in adult mice. Ethanol treatment at P7 induces deficits in LTP, memory and social recognition in adult mice and these deficits were prevented by Bix pretreatment at P7. Together, these findings provide physiological and behavioral evidence that the long-term harmful consequences on brain function after ethanol exposure with a third trimester equivalent have an epigenetic origin. PMID:25017367

Subbanna, Shivakumar; Basavarajappa, Balapal S

2014-11-01

188

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

189

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

190

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...

191

TOP1 and 2, polysaccharides from Taraxacum officinale, attenuate CCl(4)-induced hepatic damage through the modulation of NF-kappaB and its regulatory mediators.  

PubMed

In this work, we estimate the inhibitory effect of two polysaccharides from Taraxacum officinale (TOP) on CCl(4)-induced oxidative stress and inflammation in Sprague-Dawley rats. TOP1 and 2 (304, 92 mg/kg bw) were administered for 7 days via a stomach sonde, and hepatitis was induced by a single dose of CCl(4) (50% CCl(4)/olive oil; 0.5 mL/kg bw) administration. CCl(4) significantly elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Histopathological observation further revealed that CCl(4)-induced moderate levels of inflammatory cell infiltration, centrilobular fatty change, apoptosis, and necrosis. However, TOPs pretreatment markedly decreased AST and ALT activities as well as hepatic lesions. TOPs also increased free radical scavenging activity, as exhibited by a lowered TBARS concentration. TOPs pretreatment also reversed other hepatitis-associated symptoms, including GSH depletion, inhibited anti-oxidative enzyme activities, up-regulation of NF-kappaB and increased expression of its regulatory inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta. These results suggest that TOPs have a hepatoprotective effect by modulating inflammatory responses and ameliorating oxidative stress. PMID:20170702

Park, Chung Mu; Youn, Hyun Joo; Chang, Hee Kyung; Song, Young Sun

2010-05-01

192

Apoptotic Damage of Pancreatic Ductal Epithelia by Alcohol and Its Rescue by an Antioxidant  

PubMed Central

Alcohol abuse is a major cause of pancreatitis. However alcohol toxicity has not been fully elucidated in the pancreas and little is known about the effect of alcohol on pancreatic ducts. We report the molecular mechanisms of ethanol-induced damage of pancreatic duct epithelial cells (PDEC). Ethanol treatment for 1, 4, and 24 h resulted in cell death in a dose-dependent manner. The ethanol-induced cell damage was mainly apoptosis due to generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP), and activation of caspase-3 enzyme. The antioxidant N-acetylcysteine (NAC) attenuated these cellular responses and reduced cell death significantly, suggesting a critical role for ROS. Acetaldehyde, a metabolic product of alcohol dehydrogenase, induced significant cell death, depolarization of MMP, and caspase-3 activation as ethanol and this damage was also averted by NAC. Reverse transcription-polymerase chain reaction revealed the expression of several subtypes of alcohol dehydrogenase and acetaldehyde dehydrogenase. Nuclear magnetic resonance spectroscopy data confirmed the accumulation of acetaldehyde in ethanol-treated cells, suggesting that acetaldehyde formation can contribute to alcohol toxicity in PDEC. Finally, ethanol increased the leakage of PDEC monolayer which was again attenuated by NAC. In conclusion, ethanol induces apoptosis of PDEC and thereby may contribute to the development of alcohol-induced pancreatitis. PMID:24244749

Seo, Jong Bae; Gowda, G. A. Nagana; Koh, Duk-Su

2013-01-01

193

Hepatitis C  

MedlinePLUS Videos and Cool Tools

... impairs liver function and may necessitate a liver transplant • 1-5 of persons might die from the ... Hepatitis C is a leading indication for liver transplants. Diagnosis It is often difficult to diagnose hepatitis ...

194

Viral Hepatitis  

MedlinePLUS

... cleaned properly Eating raw shellfish that came from sewage-contaminated water You can get hepatitis B if ... commonly seen in the United States. Hepatitis A prevention Get vaccinated. People with certain risk factors and ...

195

Hepatitis C  

MedlinePLUS

... can't be spread unless a person has direct contact with infected blood. This means a person who ... hepatitis C? Hepatitis C is usually spread through direct contact with the blood of a person who has ...

196

Antioxidant effect of dry olive ( Olea europaea L.) leaf extract on ethanol-induced gastric lesions in rats  

Microsoft Academic Search

Previous studies demonstrated that the damaging action of absolute ethanol could be attributed to the enhancement in the reactive\\u000a oxygen species, increase in lipid peroxidation and inhibition of antioxidative enzyme activity. In this study we investigated\\u000a the mechanism of protective effect of olive leaf extract (OLE), a natural antioxidant, on gastric mucosal damage induced by\\u000a absolute ethanol in rats. OLE

D. Dekanski; S. Risti?; D. M. Mitrovi?

2009-01-01

197

Scrub typhus hepatitis confirmed by immunohistochemical staining  

PubMed Central

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi (O. tsutsugamushi). We report herein the case of a woman who presented with fever and elevated serum levels of liver enzymes and who was definitively diagnosed with scrub typhus by histopathological examination of liver biopsy specimens, serological tests and nested polymerase chain reaction. Immunohistochemical staining using a monoclonal anti-O. tsutsugamushi antibody showed focally scattered positive immunoreactions in the cytoplasm of some hepatocytes. This case suggests that scrub typhus hepatitis causes mild focal inflammation due to direct liver damage without causing piecemeal necrosis or interface hepatitis. Thus, scrub typhus hepatitis differs from acute viral hepatitis secondary to liver damage due to host immune responses, which causes severe lobular disarray with diffuse hepatocytic degeneration, necrosis and apoptosis as well as findings indicative of hepatic cholestasis, such as hepatic bile plugs or brown pigmentation of hepatocytes. PMID:23049227

Chung, Jong-Hoon; Lim, Sung-Chul; Yun, Na-Ra; Shin, Sung-Heui; Kim, Choon-Mee; Kim, Dong-Min

2012-01-01

198

Ethanol induced acetylation of histone at G9a exon1 and G9a-mediated histone H3 dimethylation leads to neurodegeneration in neonatal mice.  

PubMed

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, S; Nagre, N N; Shivakumar, M; Umapathy, N S; Psychoyos, D; Basavarajappa, B S

2014-01-31

199

Involvement of the Beta-Endorphin Neurons of the Hypothalamic Arcuate Nucleus in Ethanol-Induced Place Preference Conditioning in Mice  

PubMed Central

Background Increasing evidence indicates that mu- and delta-opioid receptors are decisively involved in the retrieval of memories underlying conditioned effects of ethanol. The precise mechanism by which these receptors participate in such effects remains unclear. Given the important role of the proopiomelanocortin (POMc)-derived opioid peptide beta-endorphin, an endogenous mu- and delta-opioid receptor agonist, in some of the behavioral effects of ethanol, we hypothesized that beta-endorphin would also be involved in ethanol conditioning. Methods In the present study we treated female Swiss mice with estradiol valerate (EV), which induces a neurotoxic lesion of the beta-endorphin neurons of the hypothalamic arcuate nucleus (ArcN). These mice were compared to saline-treated controls to investigate the role of beta-endorphin in the acquisition, extinction and reinstatement of ethanol (0 or 2 g/kg; i.p.)-induced conditioned place preference (CPP). Results Immunohistochemical analyses confirmed a decreased number of POMc-containing neurons of the ArcN with EV treatment. EV did not affect the acquisition or reinstatement of ethanol-induced CPP, but facilitated its extinction. Behavioral sensitization to ethanol, seen during the conditioning days, was not present in EV-treated animals. Conclusions The present data suggest that ArcN beta-endorphins are involved in the retrieval of conditioned memories of ethanol, and are implicated in the processes that underlie extinction of ethanol-cue associations. Results also reveal a dissociated neurobiology supporting behavioral sensitization to ethanol and its conditioning properties, as a beta-endorphin deficit affected sensitization to ethanol, while leaving acquisition and reinstatement of ethanol-induced CPP unaffected. PMID:22014186

Pastor, Raúl; Font, Laura; Miquel, Marta; Phillips, Tamara J.; Aragon, Carlos M.G.

2014-01-01

200

Hepatitis B  

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... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

201

Coenzyme Q10 rescues ethanol-induced corneal fibroblast apoptosis through the inhibition of caspase-2 activation.  

PubMed

Recent studies indicate that caspase-2 is involved in the early stages of apoptosis, particularly before the occurrence of mitochondrial damage. Here we report the important role of the coenzyme Q10 (CoQ10) on the activity of caspase-2 upstream of mitochondria in ethanol (EtOH)-treated corneal fibroblasts. After EtOH exposure, cells produce excessive reactive oxygen species formation, p53 expression, and most importantly, caspase-2 activation. After the activation of the caspase-2, the cells exhibited hallmarks of apoptotic pathway, such as mitochondrial damage and translocation of Bax and cytochrome c, which were then followed by caspase-3 activation. By pretreating the cells with a cell-permeable, biotinylated pan-caspase inhibitor, we identified caspase-2 as an initiator caspase in EtOH-treated corneal fibroblasts. Loss of caspase-2 inhibited EtOH-induced apoptosis. We further found that caspase-2 acts upstream of mitochondria to mediate EtOH-induced apoptosis. The loss of caspase-2 significantly inhibited EtOH-induced mitochondrial dysfunction, Bax translocation, and cytochrome c release from mitochondria. The pretreatment of CoQ10 prevented EtOH-induced caspase-2 activation and mitochondria-mediated apoptosis. Our data demonstrated that by blocking caspase-2 activity, CoQ10 can protect the cells from mitochondrial membrane change, apoptotic protein translocation, and apoptosis. Taken together, EtOH-induced mitochondria-mediated apoptosis is initiated by caspase-2 activation, which is regulated by CoQ10. PMID:23430247

Chen, Chun-Chen; Liou, Shiow-Wen; Chen, Chi-Chih; Chen, Wen-Chung; Hu, Fung-Rong; Wang, I-Jong; Lin, Shing-Jong

2013-04-26

202

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

PubMed

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

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

2014-01-01

203

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

204

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

205

Hepatitis C and bile duct loss.  

PubMed Central

AIM: To assess whether bile duct loss is associated with the bile duct damage induced by chronic hepatitis C. METHODS: Sections were examined from 171 liver biopsy specimens from patients with chronic hepatitis C, 98 biopsy specimens from patients with chronic hepatitis B, 25 postmortem specimens from patients with no evidence of liver disease, and 23 patients who underwent protocol liver biopsy at the time of cholecystectomy. RESULTS: The bile duct:portal tract ratio for the hepatitis C group was 0.89, for the hepatitis B group was 0.93 and for the two control groups was 0.96 and 0.90, respectively. The ratio was lower in the hepatitis C group than in the other three. In no case of chronic hepatitis C was the ratio less than 0.60. In the hepatitis C group greater bile duct loss was seen in cirrhotic patients. CONCLUSIONS: Hepatitis C is associated with bile duct loss and this was related to the stage of the disease. However, in the cases studied this did not reach what is generally considered to be significant (that is, greater than 50% of portal tracts lacking bile ducts). This does not preclude a contributory effect of hepatitis C to bile duct loss in the presence of other risk factors, especially in liver transplant recipients. PMID:8943752

Goldin, R D; Patel, N K; Thomas, H C

1996-01-01

206

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 ...

207

Hepatitis C  

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... who had hepatitis C Received a tattoo or acupuncture with needles that were not disinfected properly after ... have a tattoo license or permit or an acupuncture license) Received an organ transplant from a donor ...

208

Hepatitis E  

MedlinePLUS

... hepatitis E virus is transmitted mainly through contaminated drinking water. It is usually a self-limiting infection and ... faecal-oral route due to faecal contamination of drinking water. Other transmission routes have been identified, which include: ...

209

Fenugreek (Trigonella foenum graecum) seed extract prevents ethanol-induced toxicity and apoptosis in Chang liver cells.  

PubMed

The protective effect of a polyphenolic extract of fenugreek seeds (FPEt) against ethanol (EtOH)-induced toxicity was investigated in human Chang liver cells. Cells were incubated with either 30 mM EtOH alone or together in the presence of seed extract for 24 h. Assays were performed in treated cells to evaluate the ability of seeds to prevent the toxic effects of EtOH. EtOH treatment suppressed the growth of Chang liver cells and induced cytotoxicity, oxygen radical formation and mitochondrial dysfunction. Reduced glutathione (GSH) concentration was decreased significantly (P < 0.05) while oxidized glutathione (GSSG) concentration was significantly elevated in EtOH-treated cells as compared with normal cells. Incubation of FPEt along with EtOH significantly increased cell viability in a dose-dependent manner, caused a reduction in lactate dehydrogenase leakage and normalized GSH/GSSG ratio. The extract dose-dependently reduced thiobarbituric acid reactive substances formation. Apoptosis was observed in EtOH-treated cells while FPEt reduced apoptosis by decreasing the accumulation of sub-G1 phase cells. The cytoprotective effects of FPEt were comparable with those of a positive control silymarin, a known hepatoprotective agent. The findings suggest that the polyphenolic compounds of fenugreek seeds can be considered cytoprotective during EtOH-induced liver damage. PMID:16574673

Kaviarasan, Subramanian; Ramamurty, Nalini; Gunasekaran, Palani; Varalakshmi, Elango; Anuradha, Carani Venkatraman

2006-01-01

210

Ethanol-induced impairments in receptor-mediated endocytosis of asialoorosomucoid in isolated rat hepatocytes: Time course of impairments and recovery after ethanol withdrawal  

SciTech Connect

Chronic ethanol administration markedly impairs the process of receptor-mediated endocytosis (RME) of a representative asialoglycoprotein, asialoorosomucoid (ASOR), by the liver. In this study, we further characterized these impairments by identifying the time of onset for ethanol-induced changes in RME as well as establishing the time course for recovery to normal endocytotic values after ethanol withdrawal. Ethanol administration for 3 days did not alter any aspect of endocytosis examined in this study. After feeding ethanol to rats for 7 days, however, significant decreases in amounts of ligand bound, internalized, and degraded were apparent. These impairments persisted throughout the 5-week feeding study although the effects were somewhat attenuated with more prolonged ethanol feeding. In addition, an accumulation of intracellular receptors was observed in ethanol-fed animals relative to controls after 7 days of ethanol feeding. In all cases, recovery of endocytotic values to control levels was partially completed after 2 to 3 days of refeeding control diet and was fully completed after 7 days of refeeding. These results indicate that ethanol feeding for as little as 7 days profoundly impairs the process of RME by the liver. These impairments can be reversed after refeeding control diet for 7 days.

Casey, C.A.; Kragskow, S.L.; Sorrell, M.F.; Tuma, D.J.

1989-04-01

211

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

212

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

213

Hepatitis A  

Microsoft Academic Search

\\u000a Although hepatitis A is arguably among the most ancient of human diseases and among the first to have been recorded by physicians,\\u000a the responsible infectious agent, a unique picornavirus, hepatitis A virus (HAV), was identified less than 40 years ago (Feinstone\\u000a et al. 1973). The discovery of the virus built on decades of previous research led by investigators such as

Leonard N. Binn; Stanley M. Lemon

214

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

215

Delta agent (Hepatitis D)  

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216

Protective effects of melatonin against ethanol-induced reactive gliosis in hippocampus and cortex of young and aged rats.  

PubMed

Evidence has been accumulated indicating that chronic ethanol consumption leads to direct or indirect changes in the viability of central nervous system cells. The effects of aging and chronic ethanol consumption on glial markers [glial fibrillary acidic protein (GFAP) and S100B] and oxidant and antioxidant status of rats were studied. Furthermore, protective effects of melatonin against aging and alcohol consumption were also assayed. Chronic ethanol administration to young and aged rats produced an increase in lipid peroxidation, and a decline in glutathione (GSH) levels, which was significantly reversed by the co-administration of melatonin. Lipid peroxidation status was markedly affected in aged rats treated with alcohol compared to the young rats. An age-related increase in GFAP and S100B levels were found in the cortex and hippocampus. Long-term alcohol exposure resulted in distinct elevation in GFAP content in young rats (P < 0.01) while there was less increase in the cortex of aged rats (P < 0.05). In old rats, hippocampal GFAP levels were not significantly changed by alcohol treatment (P > 0.05). Co-administration of melatonin with alcohol significantly reduced GFAP contents both in the hippocampus (P < 0.01) and cortex (P < 0.001) of aged rats. No significant effects of alcohol treatment were found on the levels of neuron-specific enolase (NSE) in aged rats. This finding suggests that melatonin exerts its protective effect on injured nervous tissues by scavenging free radicals and stabilizing glial activity against the damaging effects of ethanol and aging. Furthermore, this work suggests that the signal to initiate gliosis is mediated, at least indirectly, by free radical formation. PMID:15899254

Baydas, Giyasettin; Tuzcu, Mehmet

2005-07-01

217

Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention  

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... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

218

[Hepatic encephalopathy].  

PubMed

Hepatic encephalopathy (EH) is a severe complication of hepatic cirrhosis that is characterized by multiple neuropsychiatric manifestations. EH is usually triggered by a precipitating factor and occurs in patients with severely impaired hepatic function. Minimal EH is characterized by minor cognitive impairments that are difficult to specify but represent a risk for the patients. The primary pathophysiological mechanism of EH is considered to be an increase in blood ammonia with an impairment in the patency of the blood-brainbarrier and its metabolism to glutamine in astrocytes. The diagnosis is clinical and neuroimaging techniques can be complementary. The diagnosis of minimal EH requires specific neurocognitive tests. The clinical evaluation should be directed towards identifying the trigger. Nonabsorbable disaccharides and rifaximin constitute the treatment of choice, along with prophylaxis for new episodes. PMID:25087716

Córdoba, Juan; Mur, Rafael Esteban

2014-07-01

219

Differences in sensitivity to ethanol-induced conditioned taste aversions emerge after pre- or post-pubertal gonadectomy in male and female rats  

PubMed Central

We have previously demonstrated that gonadectomy either prior to (early) or after (late) puberty elevated ethanol consumption in males to levels similar to intact adult females—effects that were attenuated by testosterone replacement. To assess whether alterations in the aversive effects of ethanol might contribute to gonadectomy-associated increases in ethanol intake in males, the present study examined the impact of gonadectomy on conditioned taste aversions (CTA) to ethanol in male and female Sprague-Dawley rats. Animals were gonadectomized, received sham surgery (SH) or non-manipulated (NM) on postnatal (P) day 23 (early) or 67 (late) and tested for CTA to ethanol in adulthood. Water-deprived rats were given 1 hr access every-other-day to 10% sucrose followed by an injection of ethanol (0, 1 g/kg) for 5 test sessions. Test data were analyzed to determine the first day significant aversions emerged in each ethanol group (i.e., sucrose intakes significantly less than their saline-injected counterparts). Early gonadectomized males acquired the CTA more rapidly than did early SH and NM males (day 1 vs 3 and 4 respectively), whereas a gonadectomy-associated enhancement in ethanol CTA was not evident in late males. Among females, gonadectomy had little impact on ethanol-induced CTA, with females in all groups showing an aversion by the first or second day, regardless of surgery age. These data suggest that previously observed elevations in ethanol intake induced by either pre- or post-pubertal gonadectomy in males are not related simply to gonadectomy-induced alterations in the aversive effects of ethanol indexed via CTA. PMID:23195111

Morales, Melissa; Spear, Linda P.

2012-01-01

220

Nociceptin/orphanin FQ decreases glutamate transmission and blocks ethanol-induced effects in the central amygdala of naive and ethanol-dependent rats.  

PubMed

The central nucleus of the amygdala (CeA) mediates several addiction-related processes and nociceptin/orphanin FQ (nociceptin) regulates ethanol intake and anxiety-like behaviors. Glutamatergic synapses, in the CeA and throughout the brain, are very sensitive to ethanol and contribute to alcohol reinforcement, tolerance, and dependence. Previously, we reported that in the rat CeA, acute and chronic ethanol exposures significantly decrease glutamate transmission by both pre- and postsynaptic actions. In this study, using electrophysiological techniques in an in vitro CeA slice preparation, we investigated the effects of nociceptin on glutamatergic transmission and its interaction with acute ethanol in naive and ethanol-dependent rats. We found that nociceptin (100-1000?nM) diminished basal-evoked compound glutamatergic receptor-mediated excitatory postsynaptic potentials (EPSPs) and spontaneous and miniature EPSCs (s/mEPSCs) by mainly decreasing glutamate release in the CeA of naive rats. Notably, nociceptin blocked the inhibition induced by acute ethanol (44?mM) and ethanol blocked the nociceptin-induced inhibition of evoked EPSPs in CeA neurons of naive rats. In neurons from chronic ethanol-treated (ethanol-dependent) rats, the nociceptin-induced inhibition of evoked EPSP amplitude was not significantly different from that in naive rats. Application of [Nphe1]Nociceptin(1-13)NH2, a nociceptin receptor (NOP) antagonist, revealed tonic inhibitory activity of NOP on evoked CeA glutamatergic transmission only in ethanol-dependent rats. The antagonist also blocked nociceptin-induced decreases in glutamatergic responses, but did not affect ethanol-induced decreases in evoked EPSP amplitude. Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses. PMID:24169802

Kallupi, Marsida; Varodayan, Florence P; Oleata, Christopher S; Correia, Diego; Luu, George; Roberto, Marisa

2014-04-01

221

The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 prevents reinstatement of extinguished ethanol-induced conditioned place preference in mice.  

PubMed

Alcohol dependence is considered a major public health problem in modern societies. The role for glutamatergic neurotransmission in the reinforcing effects of ethanol is becoming increasingly evident. Our previous findings have shown that in rats, the mGluR7 positive allosteric agonist AMN082, but not its allosteric antagonist MMPIP, prevented ethanol consumption and preference in the two-bottle choice paradigm. This study was conducted to determine the effects of AMN082 and MMPIP on the extinction and reinstatement of ethanol-elicited place preference (CPP) in C57BL/6 mice. AMN082 and MMPIP were administered during extinction of ethanol CPP to determine whether mGluR7 signaling is required. Furthermore, the effects of AMN082 and MMPIP on reinstatement of CPP were also evaluated. Finally, spontaneous locomotor activity and ethanol pharmacokinetics were assessed following systemic administration of AMN082 and MMPIP. Our results indicate that mGluR7 pharmacological modulation had no effect on ethanol-elicited CPP extinction. In contrast, mGluR7 activation using AMN082 reduced ethanol-induced CPP reinstatement, an effect reversed by co-administration of MMPIP. Collectively, these results indicate, for the first time, that activation of the mGluR7 receptor is effective in reducing the reinstatement of conditioned rewarding effects of ethanol. Taken together, the efficacy of AMN082 on the various phases of alcohol-CPP could represent an interesting pharmacological approach and could open a new line of research for the development of therapies to reduce ethanol intake in patients. PMID:22269296

Bahi, Amine

2012-04-01

222

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

PubMed

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

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

2014-01-01

223

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

224

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

225

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

PubMed Central

A large body of research has aimed to determine the neurochemical factors driving differential sensitivity to ethanol between individuals in an attempt to find predictors of ethanol abuse vulnerability. Here we find that the locomotor activating effects of ethanol are markedly greater in DBA/2J compared to C57BL/6J mice, although it is unclear as to what neurochemical differences between strains mediate this behavior. Dopamine elevations in the nucleus accumbens and caudate-putamen regulate locomotor behavior for most drugs, including ethanol; thus, we aimed to determine if differences in these regions predict strain differences in ethanol-induced locomotor activity. Previous studies suggest that ethanol interacts with the dopamine transporter, potentially mediating its locomotor activating effects; however, we found that ethanol had no effects on dopamine uptake in either strain. Ex vivo voltammetry allows for the determination of ethanol effects on presynaptic dopamine terminals, independent of drug-induced changes in firing rates of afferent inputs from either dopamine neurons or other neurotransmitter systems. However, differences in striatal dopamine dynamics did not predict the locomotor-activating effects of ethanol, since the inhibitory effects of ethanol on dopamine release were similar between strains. There were differences in presynaptic dopamine function between strains, with faster dopamine clearance in the caudate-putamen of DBA/2J mice; however, it is unclear how this difference relates to locomotor behavior. Because of the role of the dopamine system in reinforcement and reward learning, differences in dopamine signaling between the strains could have implications for addiction-related behaviors that extend beyond ethanol effects in the striatum. PMID:24349553

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

2013-01-01

226

Effects of cysteine and antioxidants on the hepatic redox-state, acetaldehyde and triglyceride levels after acute ethanol dosing.  

PubMed

Cysteine and the synthetic antioxidants butylated hydroxytoluene (BHT) and N,N'-diphenyl-phenylenediamine (DPPD) have been found to protect against the increase in hepatic triglycerides caused by acute ethanol administration (2 g/kg/i.p.) in rats. None of these agents affected the ethanol-induced increase in the hepatic redox-state, measured as lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios, and there was no influence of any of the compounds on ethanol metabolism. Of the three agents tested, only cysteine was found to lower the liver acetaldehyde concentration after ethanol administration, confirming reports that trapping of acetaldehyde can protect against ethanol hepatotoxicity. The protective action of the anti-oxidants suggests that lipid peroxidation (probably initiated by acetaldehyde) is an important event in the pathogenesis of acute alcoholic fatty liver. PMID:3426693

Ryle, P R; Chakraborty, J; Thomson, A D

1987-01-01

227

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

228

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

229

Antioxidant liposoluble vitamins and carotenoids in chronic hepatitis  

Microsoft Academic Search

Background: It is known that antioxidant liposoluble vitamins and carotenoids are reduced in liver cirrhosis, but little is known about chronic viral hepatitis, where oxidative damage has to be taken into account. Methods: Fifty-five patients with chronic hepatitis, mainly C virus-related, were matched with 16 patients with biliary stones and 20 healthy controls. Plasma and liver analyses were carried out

E. Rocchi; G. Casalgrandi; A. Ronzoni; M. C. Rosa; G. Cioni; A. Marazzi; A. Manenti; S. Marchini; E. Ventura

2001-01-01

230

Acute liver damage and ecstasy ingestion  

Microsoft Academic Search

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

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

1996-01-01

231

Diclofenac hepatitis  

Microsoft Academic Search

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

P Purcell; D Henry; G Melville

1991-01-01

232

An ethanol-inducible MDR ethanol dehydrogenase/acetaldehyde reductase in Escherichia coli: structural and enzymatic relationships to the eukaryotic protein forms.  

PubMed

An ethanol-active medium-chain dehydrogenase/reductase (MDR) alcohol dehydrogenase was isolated and characterized from Escherichia coli. It is distinct from the fermentative alcohol dehydrogenase and the class III MDR alcohol dehydrogenase, both already known in E. coli. Instead, it is reminiscent of the MDR liver enzyme forms found in vertebrates and has a K(m) for ethanol of 0.7 mM, similar to that of the class I enzyme in humans, however, it has a very high k(cat), 4050 min(-1). It is also inhibited by pyrazole (K(i) = 0.2 microM) and 4-methylpyrazole (K(i)= 44 microM), but in a ratio that is the inverse of the inhibition of the human enzyme. The enzyme is even more efficient in the reverse direction of acetaldehyde reduction (K(m) = 30 microM and k(cat) = 9800 min(-1)), suggesting a physiological function like that seen for the fermentative non-MDR alcohol dehydrogenase. Growth parameters in complex media with and without ethanol show no difference. The structure corresponds to one of 12 new alcohol dehydrogenase homologs present as ORFs in the E. coli genome. Together with the previously known E. coli MDR forms (class III alcohol dehydrogenase, threonine dehydrogenase, zeta-crystallin, galactitol-1-phosphate dehydrogenase, sensor protein rspB) there is now known to be a minimum of 17 MDR enzymes coded for by the E. coli genome. The presence of this bacterial MDR ethanol dehydrogenase, with a structure compatible with an origin separate from that of yeast, plant and animal ethanol-active MDR forms, supports the view of repeated duplicatory origins of alcohol dehydrogenases and of functional convergence to ethanol/acetaldehyde activity. Furthermore, this enzyme is ethanol inducible in at least one E. coli strain, K12 TG1, with apparently maximal induction at an enthanol concentration of approximately 17 mM. Although present in several strains under different conditions, inducibility may constitute an explanation for the fairly late characterization of this E. coli gene product. PMID:10406936

Shafqat, J; Höög, J O; Hjelmqvist, L; Oppermann, U C; Ibáñez, C; Jörnvall, H

1999-07-01

233

Diamine oxidase activity and related substrates in rat liver after chronic ethanol feeding  

Microsoft Academic Search

Chronic ethanol feeding as 12% or 36% of total calories caused a dose-dependent diminution of diamine oxidase activity in rat liver. Hepatic cadaverine and histamine levels were unmodified by ethanol, whereas putrescine increased, partially in relation to the decrease in diamine oxidase activity. Such results may be of interest in view of an aggravation of ethanol-induced hepatic damage when exogenous

A. Sessa; A. Perin

1992-01-01

234

Viral hepatitis.  

PubMed

Hepatitis A is still the most frequently reported vaccine preventable disease. A reduction in the incidence will only be achieved by routine childhood vaccination rather than by targeted vaccination of high-risk groups. A larger vaccine program is warranted. Hepatitis B remains a large public health problem. Vaccination targeted to high-risk adults failed to decrease the incidence of hepatitis B virus (HBV) infection. Sexual as well as nosocomial transmission remain serious problems. Vaccine escape variants have also been identified in newborns from infected mothers who had been vaccinated at birth. Clearance of HBV infection results from complex immune mechanisms including TH1 cytokines significantly associated with HLA class II alleles. Escape HBV mutants, especially precore mutants, influence the outcome. The sequences of the promoter and other critical regions were associated with severe activity. Lamivudine is a major advance in therapy of chronic hepatitis B which was recently approved in many countries. Although drug resistant mutants may be selected during therapy, additional nucleoside analogues including adefovir are promising. Optimal combination strategies of different active compounds need to be researched. Three per cent of the world population has been infected with hepatitis C virus (HCV). Epidemiology has shifted from transfusion to non-transfusion settings. Intravenous drug abuse is currently the main risk but nosocomial infection is also of concern. Three independent factors seem associated with fibrosis progression: age, daily alcohol consumption of 50 g or more and male gender. Median duration of progression to cirrhosis is about 30 years. At the cirrhotic stage, about 3-5% of patients per year develop hepatocellular carcinoma. There is little evidence that direct cytopathicity plays a significant role in liver cell injury. HCV also infects extrahepatic cells which seems critical in the pathogenesis of the many extrahepatic manifestations. The recent identification of CD81 protein as one of the HCV receptor candidates may help us to understand how chronic HCV infection may trigger a wide spectrum of clinical manifestations, autoimmune or even lymphoproliferative, through potent continuous B cell activation in the context of various host and/or environmental cofactors. Direct measurement of HCV RNA has clarified HCV replication kinetics and variability. Among patients with chronic hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy produced a response rate of 28% among those with genotype 1 and 66% with other genotypes. Similar differences were found for combination therapy among patients who had relapsed following previous interferon (IFN) therapy. Viral load prior to treatment has been clearly shown to be predictive of response to interferon treatment, with increased viral load associated with decrease rates of response. In patients non-responsive to interferon, a second course of interferon alone has no beneficial effect whereas combination therapy may induce response in 25%. In conclusion, combination therapy should be given in all situations. Viral eradication should not be the only objective of the treatment since histological improvement may be obtained despite persisting viral replication with prolonged maintenance of antiviral therapy. PMID:17035815

Trépo, C; Zoulim, F; Pradat, P

1999-10-01

235

Betulin and betulinic acid attenuate ethanol-induced liver stellate cell activation by inhibiting reactive oxygen species (ROS), cytokine (TNF-?, TGF-?) production and by influencing intracellular signaling  

Microsoft Academic Search

Background\\/aimsLiver fibrosis has been reported to be inhibited in vivo by oleanolic and ursolic acids. However, the mechanisms of the action of those triterpenoids are poorly understood. In this study, we aimed to determine the antifibrotic potential of other triterpenes, betulin and betulinic acid, and to characterize their influence on the signal transduction pathways involved in ethanol-activated hepatic stellate cells

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

2011-01-01

236

Hepatic encephalopathy.  

PubMed

Hepatic encephalopathy (HE) represents a continuum of transient and reversible neurologic and psychiatric dysfunction. It is a reversible state of impaired cognitive function or altered consciousness in patients with liver disease or portosystemic shunting. Over the last several years, high-quality studies have been conducted on various pharmacologic therapies for HE; as more data emerge, it is hoped that HE will become a more easily treated complication of decompensated liver disease. In the interim, it is important that physicians continue to screen for minimal HE and treat patients early in addition to continuing to provide current treatments of overt HE. PMID:22541700

Khungar, Vandana; Poordad, Fred

2012-05-01

237

Hepatic hydrothorax.  

PubMed

Hepatic hydrothorax (HH) is an uncommon complication in patients with end-stage liver disease. Only 5% to 10% of patients with end-stage liver disease develop HH, which may result in dyspnea, hypoxia, and infection, and portends a poor prognosis. The most likely explanation for development is passage of fluid from the peritoneal space to the pleural space due to small diaphragmatic defects. Initial management consists of diuretics with dietary sodium restriction and thoracentesis, and a transjugular intrahepatic portosystemic shunt may ultimately be required. Afflicted patients can develop morbid and fatal complications, pose management dilemmas, and should warrant evaluation for liver transplantation. PMID:24679505

Norvell, John Paul; Spivey, James R

2014-05-01

238

Hepatic Effects of 2-Butoxyethanol in Rodents  

Microsoft Academic Search

Chronic inhalation of 2-butoxyethanol resulted in an increase in liver hemangiosarcomas and hepatic carcinomas in male mouse liver. No increase in liver neoplasia was observed in similarly exposed male and female rats or female mice. We proposed that the production of liver neoplasia in the male mouse is the result of oxidative damage secondary to the hemolytic deposition of iron

Angela M. Siesky; Lisa M. Kamendulis; James E. Klaunig

2002-01-01

239

Hepatitis B therapy  

Microsoft Academic Search

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

Hellan Kwon; Anna S. Lok

2011-01-01

240

Hepatic osteodystrophy  

PubMed Central

Summary Metabolic disturbances of bone are frequent in patients with chronic liver disease. The prevalence of osteoporosis among patients with advanced chronic liver disease is reported between 12% and 55%; it is higher in primary biliary cirrhosis. All patients with advanced liver disease should be screened for osteoporosis with a densitometry, especially if the etiology is cholestatic and in the presence of other risk factors. Clinical relevance of hepatic osteodystrophy increases after liver transplantation. After liver transplant, a rapid loss of bone mineral density can be detected in the first 6 months, followed by stabilization and slight improvement of the values. At the time of transplantation, bone density values are very important prognostic factors. Therapy of hepatic osteodystrophy is based primarily on the control of risk factors: cessation of tobacco and alcohol assumption, reduction of caffeine ingestion, exercise, supplementation of calcium and vitamin D, limitation of drugs such as loop diuretics, corticosteroids, cholestyramine. Bisphosphonates have been proposed for the therapy of osteoporosis in patients with liver disease, particularly after liver transplantation. The possible side effects of oral administration of bisphosphonates, such as the occurrence of esophageal ulcerations, are of particular concern in patients with liver cirrhosis and portal hypertension, due to the risk of gastrointestinal hemorrhage from ruptured esophageal varices, although this risk is probably overestimated. PMID:25568651

Gatta, Angelo; Verardo, Alberto; Di Pascoli, Marco; Giannini, Sandro; Bolognesi, Massimo

2014-01-01

241

Alcoholic hepatitis  

PubMed Central

Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that generally occurs after decades of harmful alcohol consumption. Less severe forms of acute AH (AAH) frequently respond to alcoholic abstinence; whereas severe AAHs are characterized by a poor prognosis: up to 40-60% of these patients die within six months. Glucocorticoids currently remain the mainstay for treating severe AAH in patients with Maddrey’s Discriminant Function score > 32. Standard contraindications include recent upper gastrointestinal bleeding, renal insufficiency and uncontrolled infections. The evaluation of concomitant viral infections (hepatitis C and B viruses) is mandatory. Liver transplantation (LT), in non-responders patients, is a possible therapeutic option for severe AAH, but it is rarely used because a 6-month abstinence period is required before listing for LT. Unfortunately, most of these patients die before the end of this sober period. In our opinion, in case of severe AAH and in case of patients with a good social support and without severe psychotic or personality disorders, the lack of pre-LT abstinence period alone should not be considered a hindrance to LT. PMID:23904876

Testino, G

2013-01-01

242

Alcoholic hepatitis.  

PubMed

Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and liver failure that generally occurs after decades of harmful alcohol consumption. Less severe forms of acute AH (AAH) frequently respond to alcoholic abstinence; whereas severe AAHs are characterized by a poor prognosis: up to 40-60% of these patients die within six months. Glucocorticoids currently remain the mainstay for treating severe AAH in patients with Maddrey's Discriminant Function score > 32. Standard contraindications include recent upper gastrointestinal bleeding, renal insufficiency and uncontrolled infections. The evaluation of concomitant viral infections (hepatitis C and B viruses) is mandatory. Liver transplantation (LT), in non-responders patients, is a possible therapeutic option for severe AAH, but it is rarely used because a 6-month abstinence period is required before listing for LT. Unfortunately, most of these patients die before the end of this sober period. In our opinion, in case of severe AAH and in case of patients with a good social support and without severe psychotic or personality disorders, the lack of pre-LT abstinence period alone should not be considered a hindrance to LT. PMID:23904876

Testino, G

2013-06-15

243

Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Turnover studies.  

PubMed Central

The effect of acute ethanol administration on rates of synthesis and utilization of hepatic glutathione (GSH) was studied in rats after a pulse of [35S]cysteine. A 35% decrease in hepatic GSH content 5h after administration of 4 g of ethanol/kg body wt. was accompanied by a 33% increase in the rate of GSH utilization. The decrease occurred without increases in hepatic oxidized glutathione (GSSG) or in the GSH/GSSG ratio. The rate of non-enzymic condensation of GSH with acetaldehyde could account for only 6% of the rate of hepatic GSH disappearance. The increased loss of [35S]GSH induced by ethanol was not accompanied by an increased turnover; rather, a 30% inhibition of GSH synthesis balanced the increased rate of loss, leaving the turnover rate unchanged. The rate of acetaldehyde condensation with cysteine in vitro occurred at about one-third of the rate of GSH loss in ethanol-treated animals. However, ethanol induced only a minor decrease in liver cysteine content, which did not precede, but followed, the decrease in GSH. The characteristics of 2-methylthiazolidine-4-carboxylic acid, the condensation product between acetaldehyde and cysteine, were studied and methodologies were developed to determine its presence in tissues. It was not found in the liver of ethanol-treated animals. Ethanol administration led to a marked increase (47%) in plasma GSH in the post-hepatic inferior vena cava, but not in its pre-hepatic segment. Data suggest that an increased loss of GSH from the liver constitutes an important mechanism for the decrease in GSH induced by ethanol. In addition, an inhibition of GSH synthesis is observed. PMID:3977847

Speisky, H; MacDonald, A; Giles, G; Orrego, H; Israel, Y

1985-01-01

244

473?Evaluating Total Serum IgE Levels in Patients with Chronic Hepatitis B and C  

PubMed Central

Background Liver disease has been considered a prominent cause of IgE elevation. Significant differences may be observed depending on the cause of liver damage. For viral hepatitis, increased IgE concentrations have been observed during acute hepatitis A and B. Chronic hepatitis B carriers may also have high IgE levels. But no data on serum IgE levels in chronic hepatitis C and hepatitis B patients have been reported. The aim of the study was to evaluate serum IgE levels in patients with chronic hepatitis C and hepatitis B and to corelate with atopic patients. Methods Serum IgE levels were determined in 568 adult patients with chronic hepatitis B, in 47 patients with chronic hepatitis C, and 311 patients with atopic diseases. Results The averages of serum IgE levels were 103,9 IU/mL in chronic hepatitis C, 95,1 IU/mL in hepatits B patients, and 126,6 IU/mL in atopic patients. There was no statistically significant difference between hepatits B and hepatits C patients. Total serum IgE levels were lower in patients with either chronic hepatitis C or hepatitis B than the atopic group. Conclusions According to the results presented, chronic hepatitis C and hepatitis B are not prominent causes of increased serum IgE values. Further studies are needed to clarify the differences and significance of IgE levels between hepatitis and atopic patients.

Köse, Sükran; Senger, Süheyla Serin; Yalcin, Arzu Didem; Cavdar, Gülsün; Atalay, Sabri; Ersan, Gürsel

2012-01-01

245

Prevalence of Hepatitis E Virus Antibodies in Patients with Chronic Hepatitis B and Chronic Hepatitis C  

Microsoft Academic Search

Objectives: To investigate the prevalence of hepatitis E virus (HEV) among patients with chronic hepatitis B and chronic hepatitis C, serum samples were collected between January and December 2004 from patients with chronic hepatitis B and chronic hepatitis C. Methods: There were 190 adult patients with chronic hepatitis B virus (HBV) and 174 with chronic hepatitis C virus (HCV) infection

A. Bayram; F. Eksi; M. Mehli; E. Sözen

2007-01-01

246

Congenital Hepatic Vascular Malformations  

Microsoft Academic Search

\\u000a Congenital hepatic vascular malformations are rare entities that result in abnormal shunting of blood through the liver. Three\\u000a different types of shunting can occur: arteriovenous (hepatic artery to hepatic vein), arterioportal (hepatic artery to portal\\u000a vein) and portovenous (portal vein to hepatic vein). Malformations result from alterations in the formation of blood vessels\\u000a during fetal development and can occur as

Guadalupe Garcia-Tsao

247

Ethanol-induced fatty liver in the rat examined by in vivo 1H chemical shift selective magnetic resonance imaging and localized spectroscopic methods.  

PubMed

In vivo 1H magnetic resonance imaging (MRI), chemical shift selective imaging (CSI), and localized (VOSY) 1H magnetic resonance spectroscopy (MRS) were used to study fatty infiltration in the livers of rats chronically fed an ethanol-containing all-liquid DeCarli-Lieber diet. Conventional total proton MRI showed a somewhat hyperintense liver for ethanol-fed rats, compared with pair-fed controls. CSI showed a dramatic increase in the fat signal intensity for ethanol-treated rats that was fairly homogeneous throughout the liver. However, CSI also showed a substantial decrease in the water signal intensity for the ethanol-treated rats compared to pair-fed control rats. 1H VOSY MR spectra also showed a 5.5-fold increase in the methylene resonance (1.3 ppm) of fat and a 50-70% decrease in the water resonance (4.8 ppm). Relative in vivo proton T1 and T2 relaxation times for the water resonance separate from the fat resonance, determined from modified VOSY experiments, were found to tend to increase and decrease, respectively, for ethanol-treated rat livers compared with controls. The decrease in hepatic water signal intensity could be accounted for by the decrease in T2 and decrease in water density due to the presence of accumulated hepatic fat (approximately 25 mg/g wet weight of liver). When ethanol was withdrawn from the chronically treated rats, fatty infiltration was observed by both CSI and VOSY spectra to revert toward control values with a half-life of 2-4 days. By day 16, however, the signal intensity for hepatic fat was still significantly higher than control levels. In vitro 1H MRS studies of chloroform-methanol extracts confirmed the 5.5-fold increase in total hepatic fat induced by the chronic ethanol treatment, and showed further that triacylglycerols were increased 7.7-fold, cholesterol was increased fourfold, and phospholipids were increased 3.3-fold, compared with liver extracts from pair-fed control rats. PMID:1501537

Ling, M; Brauer, M

1992-01-01

248

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

249

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

250

Hepatitis Foundation International  

MedlinePLUS

... OF HFI'S NEWSLETTER READ MORE... Hepatitis Patient Registry Network (HepPRN) ENGAGING INDIVIDUALS. FINDING SOLUTIONS. SAVING LIVES. HFI ... pleased to launch its new Hepatitis Patient Registry Network (HepPRN). The patient-centric registry collects self-reported ...

251

Hepatitis B Test  

MedlinePLUS

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

252

Travelers' Health: Hepatitis B  

MedlinePLUS

... HBsAg, hepatitis B surface antigen; IM, intramuscular; ELU, ELISA units of inactivated HAV; HAV, hepatitis A virus. ... Climates Humanitarian Aid Workers Humanitarian Aid Organizations During Ebola Outbreak Ebola Outbreak: Advice for Humanitarian Aid Workers ...

253

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 ...

254

Erythropoietic and hepatic porphyrias  

Microsoft Academic Search

Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10% of patients. Acute hepatic porphyrias (d-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological–psychiatric and

U. Gross; G. F. Hoffmann; M. O. Doss

2000-01-01

255

Human hereditary hepatic porphyrias  

Microsoft Academic Search

The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Some gene carriers are vulnerable to a range

Yves Nordmann; Hervé Puy

2002-01-01

256

[Epidemiology of viral hepatitis].  

PubMed

Understanding the country-specific epidemiology of disease, which may vary greatly among countries, is crucial for identifying the most appropriate preventive and control measures. An overview of the local epidemiology of viral hepatitis in Croatia is given in this paper. The overall prevalence of hepatitis B in Croatia is low (less than 2% HBsAg carriers in the general population). Hepatitis B incidence and prevalence began to decline significantly following the introduction of universal hepatitis B vaccination in 1999. Information on HBsAg seroprevalence is derived from routine testing of certain subpopulations (pregnant women, blood donors) and seroprevalence studies mostly targeted at high-risk populations. Universal childhood vaccination against hepatitis B remains the main preventive measure. We recommend testing for immunity one to two months after the third dose of hepatitis B vaccine for health-care workers. The incidence and prevalence of hepatitis C have also been declining in the general population. The main preventive measures are ensuring safety of blood products, prevention of drug abuse, and harm reduction programs for intravenous drug users. Hepatitis A incidence has declined dramatically since fifty years ago, when thousands of cases were reported annually. In the last five years, an average of twenty cases have been reported per year. The reduction of hepatitis A is a consequence of improved personal and community hygiene and sanitation. Hepatitis D has not been reported in Croatia. The risk of hepatitis D will get to be even smaller as the proportion of population vaccinated against hepatitis B builds up. Hepatitis E is reported only sporadically in Croatia, mostly in persons occupationally in contact with pigs and in travelers to endemic countries. In conclusion, Croatia is a low prevalence country for hepatitides A, B and C. Hepatitis D has not been reported to occur in Croatia and there are only sporadic cases of hepatitis E. Since hepatitis A is a rare disease occurring sporadically, which is a consequence of improved sanitation and hygiene, hepatitides B and C are the main causes of viral hepatitis in Croatia. The introduction of universal mandatory hepatitis B vaccination of schoolchildren in 1999 resulted in a decrease in the incidence of hepatitis B, which is most pronounced in adolescents and young adults, and further decrease in the incidence and prevalence is expected as the pool of susceptible individuals decreases through vaccination. The incidence of hepatitis C is decreasing as well. In spite of a relatively favorable epidemiological situation, hepatitis B and C are still a significant public health burden with an estimated 25,000 persons chronically infected with HBV and about 40,000 persons chronically infected with HCV in Croatia. PMID:24984326

Kai?, Bernard; Vilibi?-Cavlek, Tatjana; Filipovi?, Sanja Kureci?; Nemeth-Blazi?, Tatjana; Pem-Novosel, Iva; Vucina, Vesna Visekruna; Simunovi?, Aleksandar; Zajec, Martina; Radi?, Ivan; Pavli?, Jasmina; Glamocanin, Marica; Gjenero-Margan, Ira

2013-10-01

257

Ammonia: Key factor in the pathogenesis of hepatic encephalopathy  

Microsoft Academic Search

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

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

1987-01-01

258

Hepatitis C: a disease with a wide morphological spectrum?  

PubMed

We describe the pathological findings of 50 biopsies of Mexican (Mestizo, or mixed race, usually Indian and white heritage) patients with hepatitis C infection confirmed by a second generation test. Although half of the patients were asymptomatic, the histological examination revealed advanced stages of disease. Chronic active hepatitis was found in 26 cases, cirrhosis in 23, and acute hepatitis in one case. Common histological changes included steatosis, lymphoid aggregates, and apoptotic bodies, whereas indisputable bile duct damage was observed in only four cases. Comparison with other series in which different types of populations were analyzed revealed a wide morphological spectrum with respect to some histological changes and the type of hepatitis reported. The apparently contradictory results found in the literature indicate the need to apply universal histological criteria in biopsies of patients with hepatitis C. PMID:8742651

Arista-Nasr, J; Pichardo-Bahena, R; Castañeda, B; Lisker, M; Keirns, C

1996-03-01

259

Bitter correlationship between autoimmune hepatitis and smoking.  

PubMed

Cigarette smoke contains numerous toxic, carcinogenic and mutagenic chemicals, stable and unstable free radicals and reactive oxygen species (ROS) which cause biological oxidative damage. Continuous exposure to those chemicals leads to immense amount of damage to the human health either directly or indirectly. A hypothesis is advanced here that a possible explanation for developing autoimmune hepatitis (AIH) is due to regular smoking for long years of time. To examine this hypothesis, I relied on an experience of a case of a patient, as well as critical reading of the literature on smoking and different autoimmune disorders. Among the autoimmune diseases, rheumatoid arthritis (RA), multiple sclerosis (MS), thyroid disease, primary biliary cirrhosis (PBC) are reported mostly among tobacco-exposed animals. The observational and theoretical knowledge strengthen the hypothesis that smoking can be one of the causes of generating autoimmune hepatitis. This hypothesis could lead to a new diagnostic category, as well as therapeutic approaches for changing the regular smoking behavior. PMID:25543266

Bose, Tanima

2015-02-01

260

Oxidative stress and antioxidants in hepatic pathogenesis  

PubMed Central

Long term hepatitis B virus (HBV) infection is a major risk factor in pathogenesis of chronic liver diseases, including hepatocellular carcinoma (HCC). The HBV encoded proteins, hepatitis B virus X protein and preS, appear to contribute importantly to the pathogenesis of HCC. Both are associated with oxidative stress, which can damage cellular molecules like lipids, proteins, and DNA during chronic infection. Chronic alcohol use is another important factor that contributes to oxidative stress in the liver. Previous studies reported that treatment with antioxidants, such as curcumin, silymarin, green tea, and vitamins C and E, can protect DNA from damage and regulate liver pathogenesis-related cascades by reducing reactive oxygen species. This review summarizes some of the relationships between oxidative stress and liver pathogenesis, focusing upon HBV and alcohol, and suggests antioxidant therapeutic approaches. PMID:21182217

Ha, Hye-Lin; Shin, Hye-Jun; Feitelson, Mark A; Yu, Dae-Yeul

2010-01-01

261

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

262

Iron and hepatitis C  

Microsoft Academic Search

Serum iron markers are often elevated in hepatitis C virus infection, particularly in African-American persons, although the\\u000a clinical significance of this finding remains unclear. Although hepatic iron is usually only mildly elevated in hepatitis\\u000a C virus, iron overload is associated with more advanced disease, nonresponse to interferon monotherapy, and increased risk\\u000a of hepatocellular carcinoma. Iron status does not predict response

James E. Nelson; Kris V. Kowdley

2004-01-01

263

Hepatic manifestations of celiac disease  

PubMed Central

Different hepatic and biliary tract disorders may occur with celiac disease. Some have been hypothesized to share genetic or immunopathogenetic factors, such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Other hepatic changes in celiac disease may occur with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. PMID:21694844

Freeman, Hugh James

2010-01-01

264

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

265

Sun Damage  

MedlinePLUS

newsletter | contact Share | Sun Damage A A A The sun has a profound effect over years of exposure on the skin, causing premature ... changes. Exposure to ultraviolet (UV) light from the sun accounts for most premature skin aging. Many skin ...

266

Potential in vitro Protective Effect of Quercetin, Catechin, Caffeic Acid and Phytic Acid against Ethanol-Induced Oxidative Stress in SK-Hep-1 Cells  

PubMed Central

Phytochemicals have been known to exhibit potent antioxidant activity. This study examined cytoprotective effects of phytochemicals including quercetin, catechin, caffeic acid, and phytic acid against oxidative damage in SK-Hep-1 cells induced by the oxidative and non-oxidative metabolism of ethanol. Exposure of the cells to excess ethanol resulted in a significant increase in cytotoxicity, reactive oxygen species (ROS) production, lipid hydroperoxide (LPO), and antioxidant enzyme activity. Excess ethanol also caused a reduction in mitochondrial membrane potential (MMP) and the quantity of reduced glutathione (GSH). Co-treatment of cells with ethanol and quercetin, catechin, caffeic acid and phytic acid significantly inhibited oxidative ethanol metabolism-induced cytotoxicity by blocking ROS production. When the cells were treated with ethanol after pretreatment of 4-methylpyrazole (4-MP), increased cytotoxicity, ROS production, antioxidant enzyme activity, and loss of MMP were observed. The addition of quercetin, catechin, caffeic acid and phytic acid to these cells showed suppression of non-oxidative ethanol metabolism-induced cytotoxicity, similar to oxidative ethanol metabolism. These results suggest that quercetin, catechin, caffeic acid and phytic acid have protective effects against ethanol metabolism-induced oxidative insult in SK-Hep-1 cells by blocking ROS production and elevating antioxidant potentials. PMID:24009840

Lee, Ki-Mo; Kang, Hyung-Sik; Yun, Chul-Ho; Kwak, Hahn-Shik

2012-01-01

267

Reversed light-dark cycle and cage enrichment effects on ethanol-induced deficits in motor coordination assessed in inbred mouse strains with a compact battery of refined tests  

PubMed Central

The laboratory environment existing outside the test situation itself can have a substantial influence on results of some behavioral tests with mice, and the extent of these influences sometimes depends on genotype. For alcohol research, the principal issue is whether genotype-related ethanol effects will themselves be altered by common variations in the lab environment or instead will be essentially the same across a wide range of lab environments. Data from 20 inbred strains were used to reduce an original battery of seven tests of alcohol intoxication to a compact battery of four tests: the balance beam and grip strength with a 1.25 g/kg ethanol dose and the accelerating rotarod and open-field activation tests with 1.75 g/kg. The abbreviated battery was then used to study eight inbred strains housed under a normal or reversed light-dark cycle, or a standard or enriched home cage environment. The light-dark cycle had no discernable effects on any measure of behavior or response to alcohol. Cage enrichment markedly improved motor coordination in most strains. Ethanol-induced motor coordination deficits were robust; the well documented strain-dependent effects of ethanol were not altered by cage enrichment. PMID:21664382

Munn, Elizabeth; Bunning, Mark; Prada, Sofia; Bohlen, Martin; Crabbe, John C.; Wahlsten, Douglas

2011-01-01

268

A functional analysis of the yeast ubiquitin ligase Rsp5: the involvement of the ubiquitin-conjugating enzyme Ubc4 and poly-ubiquitination in ethanol-induced down-regulation of targeted proteins.  

PubMed

Rsp5 is an essential ubiquitin ligase in Saccharomyces cerevisiae. We have found that the Ala401Glu rsp5 mutant is hypersensitive to various stresses, suggesting that Rsp5 is a key enzyme for yeast cell growth under stress conditions. The ubiquitination and the subsequent degradation of stress-induced misfolded proteins are indispensable for cell survival under stress conditions. In this study, we analyzed the ubiquitin-conjugating enzyme Ubc4 and the poly-ubiquitination of targeted proteins involved in the function of Rsp5 under ethanol stress conditions. Ubc4 was found to be important in yeast cell growth and poly-ubiquitination of the bulk proteins in the presence of ethanol. The general amino acid permease Gap1 is poly-ubiquitinated via Lys63 and is down-regulated after the addition of ammonium ions through a process requiring Rsp5. We found that Gap1 was removed from the plasma membrane in the presence of ethanol in a Rsp5-dependent manner, and that the disappearance of Gap1 required Ubc4 and involved the lysine residues of ubiquitin. Our results also indicate that Lys6 of ubiquitin might inhibit the disappearance of Gap1. These results suggest that Rsp5 down-regulates the ethanol-induced misfolded forms of Gap1. In addition, it appears that the substrates of Rsp5 are appropriately poly-ubiquitinated via different lysine residues of ubiquitin under various growth conditions. PMID:19809202

Hiraishi, Hiroyuki; Okada, Masahiro; Ohtsu, Iwao; Takagi, Hiroshi

2009-10-01

269

Erythropoietic and hepatic porphyrias.  

PubMed

Porphyrias are divided into erythropoietic and hepatic manifestations. Erythropoietic porphyrias are characterized by cutaneous symptoms and appear in early childhood. Erythropoietic protoporphyria is complicated by cholestatic liver cirrhosis and progressive hepatic failure in 10%, of patients. Acute hepatic porphyrias (delta-aminolaevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) are characterized by variable extrahepatic gastrointestinal, neurological-psychiatric and cardiovascular manifestations requiring early diagnosis to avoid life-threatening complications. Acute hepatic porphyrias are pharmacogenetic and molecular regulatory diseases (without porphyrin accumulation) mainly induced by drugs, sex hormones, fasting or alcohol. The disease process depends on the derepression of hepatic delta-aminolaevulinic acid synthase following haem depletion. In contrast to the acute porphyrias, nonacute, chronic hepatic porphyrias such as porphyria cutanea tarda are porphyrin accumulation disorders leading to cutaneous symptoms associated with liver disease, especially caused by alcohol or viral hepatitis. Alcohol, oestrogens, haemodialysis, hepatitis C and AIDS are triggering factors. Porphyria cutanea tarda is the most common porphyria, followed by acute intermittent porphyria and erythropoietic protoporphyria. The molecular genetics of the porphyrias is very heterogenous. Nearly every family has its own mutation. The mutations identified account for the corresponding enzymatic deficiencies, which may remain clinically silent throughout life. Thus, the recognition of the overt disorder with extrahepatic manifestations depends on the demonstration of biochemical abnormalities due to these primary defects and compensatory hepatic overexpression of hepatic delta-aminolaevulinic acid synthase in the acute porphyrias. Consequently, haem precursors are synthesized in excess. The increased metabolites upstream of the enzymatic defect are excreted into urine and faeces. The diagnosis is based on their evaluation. Primary enzymatic or molecular analyses are noncontributary and may be misleading. Acute polysymptomatic exacerbations accompany a high excretory constellation of porphyrin precursors delta-aminolaevulinic acid and porphobilinogen. Homozygous or compound heterozygous variants of acute hepatic porphyrias may already manifest in childhood. PMID:11117426

Gross, U; Hoffmann, G F; Doss, M O

2000-11-01

270

Hepatitis C and Incarceration  

MedlinePLUS

... or other equipment, including cookers, cottons, ties, or water to inject drugs. • Do not share razors, toothbrushes, ... t cleaning kill the Hepatitis C virus? Bleaching, boiling, ... infected with the Hepatitis C virus at some point in time. If this test is positive for ...

271

Enteric hepatitis viruses  

PubMed Central

Hepatitis viruses are infectious agents that can infect liver and cause inflammation. The infection triggers immune response against infected cells that leads to the destruction of hepatic cells. This destruction has two consequences: leaking ALT and AST liver enzymes which increases during the course of disease and accumulation of bilirubin- a red pigmented compound released from dead red cells- which causes the yellow coloration of eyes and skin. These viruses transmit through diverse routes i.e. blood transfusion, sexual contacts and consuming water or food contaminated by feces. Enteric hepatitis viruses use the latter route for transmission; hence their outbreaks are more common in underdeveloped countries. There are currently two distinguished enteric hepatitis viruses, hepatitis A and hepatitis E. These viruses belong to different family of viruses and their epidemiological characteristics are different. These infections can be diagnosed by an ELISA for IgM antibody. A vaccine has been developed in last decade of twentieth century for hepatitis A virus, which is administered mostly in the developed world i.e. U.S and Japan. Treatment for these infections is mostly supportive; however, in the case of fulminant hepatitis the liver transplantation might be necessary. PMID:24834192

Tahaei, Seyed Mohammad Ebrahim; Zali, Mohammad Reza

2012-01-01

272

Hepatic porphyrias in children  

Microsoft Academic Search

Clinically overt hepatic porphyria is uncommon in children. The autosomal dominant acute hepatic porphyrias, acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP), are rarely present before puberty. Identification of asymptomatic children who have inherited these disorders is an important aspect of the management of the disease in their families and requires either enzymatic or DNA methods. Homozygous

G. H. Elder

1997-01-01

273

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

274

Hepatitis C: epidemiology and review of complementary/alternative medicine treatments.  

PubMed

Hepatitis C is emerging as a serious worldwide problem. In the United States the current mortality figures may triple in the next ten years, rivaling HIV. The disease has a latency of 10-30 years and symptoms or signs may not appear until cirrhosis is evident. Adequate diagnosis, including liver biopsy, is essential in assessing the current stage of the viral infection and the need for treatment. Hepatitis C may manifest as hepatic fibrosis, cirrhosis, hepatocellular carcinoma, lichen planus, glomerulonephritis, mixed cryoglobulinemia, or porphyria. The hepatic damage is due both to the cytopathic effect of the virus and the inflammatory changes secondary to immune activation. The use of the botanical components glycyrrhizin, catechin, silymarin and phytosterols, and the antioxidants N-acetylcysteine and vitamin E are reviewed for their efficacy in treating chronic hepatitis and affecting liver damage. PMID:10468647

Patrick, L

1999-08-01

275

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

276

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

PubMed

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 p53(K386)acetylation, PUMA expression and Ly6c+ cell infiltration. Subsequent to increased apoptosis, ethanol enhanced induction of pro-fibrotic markers including stellate cell activation, collagen 1 expression and extracellular matrix deposition, following CCl4 exposure. Ethanol-induced exacerbation of hepatocyte apoptosis, p53(K386) 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

2014-10-01

277

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

278

Hepatitis A FAQs  

MedlinePLUS

... the feces, or stool, of an infected person. Statistics How common is Hepatitis A in the United ... South America, Mexico, and certain parts of Asia, Africa, and Eastern Europe. CDC’s Travelers’ Health site provides ...

279

Human hereditary hepatic porphyrias.  

PubMed

The human hereditary hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Porphyrias can be classified as either hepatic or erythroid, depending on the major production site of porphyrins or their precursors. The pathogenesis of inherited hepatic porphyrias has now been defined at the molecular level. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric and/or cutaneous symptoms. Early diagnosis is of prime importance since it makes way for counselling. In this article we present an overview of recent advances on hepatic porphyrias: 5-aminolevulinic acid dehydratase deficiency porphyria, acute intermittent porphyria (AIP), porphyria cutanea tarda (PCT), hereditary coproporphyria (HC), and variegate porphyria (VP). PMID:12367763

Nordmann, Yves; Puy, Hervé

2002-11-01

280

[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

281

Benefits of Hepatitis A  

E-print Network

of Family Physicians, “Most children younger than 6 years do not show symptoms of hepatitis A. If illness does occur, the symptoms can last up to 2 months, but children do not usually have jaundice. We do know that infected children spread the hepatits A virus to the adults around them, and this can be serious. When adults are infected with hepatitis A, their symptoms can be much worse, sometimes requiring hospitalization.” The Hepatitis A Vaccine — A Safe and Effective Way to Protect Your Child According to Dr. Murphy, “Vaccinating all children is the most effective way to prevent them from spreading the infection to their family and others, and protects children as they grow older, when the illness can be more severe.” For the best protection, children and adults need two doses of the hepatitis A vaccine spaced 6 months apart. The first vaccine dose is recommended at age 12 months. The hepatitis A vaccine is very effective — nearly all of children and adults who receive both doses of the vaccine will be protected from hepatitis A. “Rates of hepatitis A in the United States have decreased by 80 % since we started vaccinating for this disease. This is a real testament to how effective this vaccine is, ” says Dr. Campos-Outcalt. The hepatitis A vaccine has an excellent safety record. This vaccine has never been known to cause any serious side effects. About 1 out of 6 children feels soreness after receiving the shot. About 1 out of 10 children may have a mild fever or poor appetite. If these problems occur, they usually last a day or two. However, vaccines like any medicine, could very rarely cause a severe allergic reaction.

Bonanni P; Boccalini S; Bechini A. Vaccination Against

282

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 ...

283

Delta hepatitis in Malaysia.  

PubMed

Sera from one hundred and fifty nine Malaysian individuals were screened for the prevalence of delta markers. These included 15 HBsAg positive homosexuals, 16 acute hepatitis B cases, 9 chronic hepatitis B patients, 13 healthy HBsAg carriers and 106 intravenous (i.v.) drug abusers, of whom 27 were positive for HBsAg only and the rest were anti-HBc IgG positive but HBsAg negative. The prevalence of delta markers in the homosexuals was found to be 6.7%, in the HBsAg positive drug abusers 17.8%, in acute hepatitis B cases 12.5%. No evidence of delta infection was detected in healthy HBsAg carriers, chronic hepatitis B cases and HBsAg negative i.v. drug abusers. With reference to i.v. drug abusers, the prevalence of delta markers was higher in Malays (23%) than in Chinese (7%) although the latter had a higher HBsAg carrier rate. Although the HBsAg carrier rate in the homosexuals was high, their delta prevalence rate was low as compared to drug abusers. In Malaysia, as in other non-endemic regions, hepatitis delta virus transmission appeared to occur mainly via the parenteral and sexual routes. This is the first time in Malaysia that a reservoir of delta infection has been demonstrated in certain groups of the population at high risk for hepatitis B. PMID:3787309

Sinniah, M; Dimitrakakis, M; Tan, D S

1986-06-01

284

Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A  

PubMed Central

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) and transforming growth factor beta (TGF-?) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-?B and TGF-? production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-?B and TGF-? production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis. PMID:25098714

Wan, Y.; Tang, M.H.; Chen, X.C.; Chen, L.J.; Wei, Y.Q.; Wang, Y.S.

2014-01-01

285

Mangafodipir Protects against Hepatic Ischemia-Reperfusion Injury in Mice  

PubMed Central

Introduction and Aim Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. Methods Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. Results Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. Conclusions Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury. PMID:22073237

Coriat, Romain; Leconte, Mahaut; Kavian, Niloufar; Bedda, Sassia; Nicco, Carole; Chereau, Christiane; Goulvestre, Claire; Weill, Bernard

2011-01-01

286

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

287

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

288

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

289

Calpain and lipopolysaccharide mediated hepatitis  

E-print Network

-mediated hepatitis model to investigate the mechanisms of hepatic neutrophil infiltration following LPS administration was developed by repeat intravenous injection of LPS at a dose of 10 mg/kg to rats. Blood was collected for hematologic and biochemical analysis...

Rose, Robert Edward

2009-06-02

290

Hepatitis B: Information for Parents  

MedlinePLUS

... is a contagious liver disease caused by the hepatitis B virus. When a person is first infected with the ... 6 months after someone is infected with the hepatitis B virus. This infection can range from a very mild ...

291

Hepatic cysticercosis: a rare entity.  

PubMed

Hepatic cysticercosis is a very rare entity; only four cases have been reported to date. High-resolution ultrasonography of the abdomen is the initial and most reliable modality for evaluation of hepatic cysticercosis. Medical therapy is the mainstay of treatment. We report a case of hepatic cysticercosis in a 28-year-old male who presented with right upper quadrant pain, fever, and jaundice. The article also describes the imaging patterns of hepatic cysticercosis based on different stages of evolution. PMID:24806312

Chaudhary, Vikas; Bano, Shahina; Kumar, Praveen; Narula, Mahender Kaur; Anand, Rama

2014-12-01

292

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

293

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

294

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

295

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 is addressed in the present paper. The ability of Lemaitre's damage law to describe low and high cycle fatigue

296

[Hepatitis E as zoonosis].  

PubMed

The hepatitis E virus (HEV) the causative agent of hepatitis E, is a non-enveloped RNA virus. HEV is transmitted through oral consumption of contaminated food and water According to the currently knowledge now be considered as zoonosis. The main reservoir of HEV are pigs, boars and deer. For the first time HEV was isolated from animals (pigs) in 1997 in the U.S. Genetic analysis of strains isolated from pigs showed high similarity to strains HEV isolated from humans. This was the first evidence showing that HEV is a zoonosis. Further studies have shown that occupational groups e.g. veterinarians, swine breeders with close contact to pigs have an increased risk for HEV infections. The additional evidence supported the zoonotic potential of HEV were reports of acute hepatitis E after the consumption of undercooked meat from deer and wild boar. Infection of HEV in the domestic pig and wild boar population in Europe is widespread. PMID:21735829

Baumann-Popczyk, Anna

2011-01-01

297

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

298

The benefit of animal models for autoimmune hepatitis.  

PubMed

Autoimmune hepatitis (AIH) is a chronic liver disease which is normally recognized during late stage of the disease. Due to limited knowledge about the onset and course of disease and need for chronic immunosuppression with significant side-effects there is a requirement for a good preclinical animal model, mirroring main characteristics of AIH. In addition to the exclusion of other liver diseases, AIH is characterized by elevated serum transaminases, specific autoantibodies and elevated gammaglobulins as well as a specific liver histopathology. A good preclinical model should mirror most of these criteria. In the last decades several models have been published using different approaches to break hepatic tolerance and induce liver damage. The induction of a chronic hepatitis similar to the human disease remained a difficult challenge. Nevertheless, these models helped to get more information about the aspects of AIH induction and liver immunology. PMID:22117631

Jaeckel, Elmar; Hardtke-Wolenski, Matthias; Fischer, Katja

2011-12-01

299

The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD)  

PubMed Central

Nonalcoholic fatty liver disease is increasingly regarded as a hepatic manifestation of metabolic syndrome, and the severity of nonalcoholic fatty liver disease seems to increase in parallel with other features of metabolic syndrome. Excess lipid accumulation in the liver cells is not only a mediator of Metabolic Syndrome and indicator of a lipid overload but also accompanied by a range of histological alterations varying from 'simple' steatosis to nonalcoholic steatohepatitis, with time progressing to manifest cirrhosis. Hepatocellular carcinoma may also occur in nonalcoholic steatohepatitis -related cirrhosis with a mortality rate similar to or worse than for cirrhosis associated with hepatitis C. This review summarizes the knowledge about the causal relationship between hepatic fat accumulation, insulin resistance, liver damage and the etiological role of hepatic fat accumulation in pathogenesis of extra- and intra-hepatic manifestations. Special emphasis is given suggestions of new targets treatment and prevention of nonalcoholic fatty liver disease. PMID:20426802

2010-01-01

300

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

301

Acute liver damage and ecstasy ingestion.  

PubMed Central

Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery. Images Figure 1 Figure 2 Figure 3 PMID:8675102

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

1996-01-01

302

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

303

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

304

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

305

4 Acute hepatitis C  

Microsoft Academic Search

Acute hepatitis C is usually a sub-clinical disease, thus it is not included in the differential diagnosis of patients with acute disease. Making the diagnosis is also diffi cult because the virus antibodies appear at later stages and many even be negative even if the patient has symptoms; at this point the diagnosis of the disease could be made with

Jay H. Hoofnagle; JUAN CARLOS RESTREPO; John Jaime; Juan Carlos; Restrepo Gutiérrez; Gutiérrez Calle

2000-01-01

306

Hepatitis C virus  

Microsoft Academic Search

Summary HepCV is the major cause of NANB PT hepatitis and is also implicated as the cause in a large proportion of sporadic cases of NANBH. Chronic infection with HepCV has also been linked to the development of hepatocellular carcinoma. Chimpanzees and marmosets are the only animals found to be experimentally infectable and the virus has not been propagated in

P. G. W. Plagemann

1991-01-01

307

Management of Hepatic Encephalopathy  

PubMed Central

Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease. PMID:21994873

Wright, G.; Chattree, A.; Jalan, R.

2011-01-01

308

Infected solitary hepatic cyst.  

PubMed

An unusual case involving an infected hepatic cyst in which the correct diagnosis was made without operation is reported. A 93-year-old woman presented with acute onset of right upper quadrant abdominal pain, mild left lower quadrant abdominal pain, diarrhea, and fever. On admission, computed tomography revealed a 15 cm solitary hepatic cyst in the anterior-superior segment of the liver with a thickened wall that enhanced with contrast media. Ultrasonography demonstrated a 15 cm anechoic lesion with a hypoechoic area in the dependent portion of the cyst and a thickened wall. The serum concentration of C-reactive protein was 24.3 mg/dL, and the white blood cell count was 13,800/microL. A diagnosis of infected hepatic cyst was suspected, and percutaneous transhepatic drainage of the cyst was performed. Milky yellow fluid was obtained and the patient's right upper quadrant abdominal pain resolved after drainage. Klebsiella pneumoniae was cultured from the drainage fluid. The patient was discharged 20 days after drainage. Infection has not recurred and the hepatic cyst has not enlarged after 18 months. PMID:14685292

Yoshida, Hiroshi; Tajiri, Takashi; Mamada, Yasuhiro; Taniai, Nobuhiko; Kawano, Youichi; Mizuguchi, Yoshiaki; Shimizu, Tetsuya; Takahashi, Tsubasa; Uchida, Eiji; Watanabe, Manabu; Uchida, Eiichi

2003-12-01

309

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

310

Hepatitis B Foundation  

MedlinePLUS

... important for anybody who is into rolex replica yoga or Pilates. Tracking down the best yoga mat rolex replica bag can occasionally be arduous ... with Hepatitis B Adults and HBV Pregnant Women Children and HBV Journal Articles Personal Stories Treatment Options ...

311

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

312

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

313

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.

314

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.

315

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

316

Hepatitis G virus infection in fulminant hepatic failure  

Microsoft Academic Search

Background—RNA sequences of the recently identified hepatitis GB virus C (HGBV-C), also named hepatitis G virus (HGV), have been detected in patients with idiopathic fulminant hepatic failure (FHF) but the role of this agent in the disease remains controversial.Aims—To investigate the presence and implications of HGV infection in a large series of Spanish patients with FHF.Patients—Sixty eight patients with FHF,

J C Sáiz; M Sans; A Mas; E Olmedo; X Forns; F X López-Labrador; J C Restrepo; J Costa; J M Salmerón; M Guilera; S Ampurdanés; J M Sánchez-Tapias; M T Jiménez de Anta; J Rodés

1997-01-01

317

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 ...

318

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 ...

319

Special report: Autoimmune hepatitis  

Microsoft Academic Search

Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Autoimmune hepatitis can be treated effectively with either prednisone alone or a lower dose of prednisone in combination\\u000a with azathioprine.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a All types of autoimmune hepatitis should be treated similarly.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a The combination schedule of prednisone and azathioprine is preferred since it is associated with fewer side effects than a\\u000a higher dose of prednisone alone.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Lifestyle

Albert J. Czaja

1999-01-01

320

[Acute hepatic vascular complications].  

PubMed

Acute hepatic vascular complications are rare. Acute portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BSC) are the leading causes. Coagulopathy and local factors are present in up to 80% of cases. Diagnosis is established by colour-coded Doppler sonography, contrast-enhanced computed tomography or magnetic resonance imaging. Patients with acute PVT present with abdominal pain and disturbed intestinal motility. In the absence of cirrhosis anticoagulation with heparin is established followed by oral anticoagulation. In severe cases, surgical thrombectomy or transjugular thrombolysis with stent shunt may be necessary. Acute or fulminant BCS may require emergency liver transplantation or a transjugular intrahepatic portosystemic stent shunt, if patients present with acute liver failure. Milder cases receive anticoagulation for thrombolysis of occluded hepatic veins. Sinusoidal obstruction syndrome (SOS) is diagnosed after total body irradiation or chemotherapy, the term SOS replacing the former veno-occlusive disease. The treatment of congenital vascular malformations, complications in the setting of OLTX as well as patients with hepatic involvement of hereditary hemorrhagic telangiectasia requires significant expertise in a multidisciplinary approach. PMID:21667100

Ochs, A

2011-07-01

321

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

322

Alcoholic hepatitis: current management.  

PubMed

Alcoholic hepatitis is an acute manifestation of alcoholic liver disease with mortality as high as 40-50% in severe cases. Patients usually have a history of prolonged alcohol abuse with or without a known history of liver disease. Although there is significant range in severity at presentation, patients with severe alcoholic hepatitis typically present with anorexia, fatigue, fever, jaundice, and ascites. The use of either pentoxifylline or corticosteroids in those with severe disease (Maddrey's discriminate function >32) has significant mortality benefit. The addition of N-acetylcysteine to corticosteroids decreases the incidences of hepatorenal syndrome, infection, and short-term mortality, but does not appear to significantly affect 6-month mortality. Nutritional support with high-calorie, high-protein diet is recommended in all patients screening positive for malnutrition. Liver transplantation for a highly selected group of patients with severe alcoholic hepatitis may be an option in the future, but is not currently recommended or available at most transplant institutions. PMID:24798996

Spengler, Erin K J; Dunkelberg, Jeffrey; Schey, Ron

2014-10-01

323

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

324

Radioembolization of hepatic tumors.  

PubMed

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 ((90)Y), 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

Kennedy, Andrew

2014-06-01

325

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

326

Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation.  

PubMed Central

The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1446866

Lucey, M R; Graham, D M; Martin, P; Di Bisceglie, A; Rosenthal, S; Waggoner, J G; Merion, R M; Campbell, D A; Nostrant, T T; Appelman, H D

1992-01-01

327

'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

328

Effects of Urtica dioica on hepatic  

E-print Network

OBJECTIVES: To evaluate the effects of Urtica dioica on hepatic ischemia-reperfusion injury. METHODS: Thirty adult male Wistar albino rats were divided into three groups: sham group (group 1), control group (group 2), and Urtica dioica group (group 3). All the rats were exposed to hepatic ischemia for 60 min, followed by 60 min of reperfusion. In group 2, a total of 2 ml/kg 0.9 % saline solution was given intraperitoneally. In group 3, a total of 2 ml/kg Urtica dioica was given intraperitoneally. At the end of the procedure, liver tissue and blood samples were taken from all rats. Serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ceruloplasmin, catalase, paraoxonase, arylesterase, and lipid hydroperoxide levels were measured. Liver tissue histopathologies were also evaluated by light microscopy. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels were significantly higher in group 2 than in group 1, and significantly lower in group 3 than in group 2. Also, group 2 had higher serum lipid hydroperoxides and ceruloplasmin levels but lower catalase, paraoxonase, and arylesterase levels than group 1. In group 3, serum lipid hydroperoxides and ceruloplasmin levels were significantly lower, and catalase, paraoxonase, and arylesterase levels were higher than those in group 2. Histopathological examination showed that liver tissue damage was significantly decreased in group 3 compared with group 2.

unknown authors

329

Theoretical Modeling for Hepatic Microwave Ablation  

PubMed Central

Thermal tissue ablation is an interventional procedure increasingly being used for treatment of diverse medical conditions. Microwave ablation is emerging as an attractive modality for thermal therapy of large soft tissue targets in short periods of time, making it particularly suitable for ablation of hepatic and other tumors. Theoretical models of the ablation process are a powerful tool for predicting the temperature profile in tissue and resultant tissue damage created by ablation devices. These models play an important role in the design and optimization of devices for microwave tissue ablation. Furthermore, they are a useful tool for exploring and planning treatment delivery strategies. This review describes the status of theoretical models developed for microwave tissue ablation. It also reviews current challenges, research trends and progress towards development of accurate models for high temperature microwave tissue ablation. PMID:20309393

Prakash, Punit

2010-01-01

330

Hepatitis C and Ozone Therapy  

Microsoft Academic Search

Hepatitis C (HCV) is a global disease with a worldwide expanding incidence and prevalence base. Of massive public health importance, hepatitis C presents supremely challenging problems in view of its adaptability and its pathogenic capacity. The unique strategies that HCV utilizes to parasitize its hosts make it a formidable enemy and therapeutic interventions need considerable sophistication to counter its progress.

Gerard V. Sunnen

331

[Hepatitis in dogs; a review].  

PubMed

As with most liver diseases, the symptoms of hepatitis in dogs are nearly always aspecific: the dogs eat less, are apathetic, sometimes have polyuria/polydipsia, and sometimes have diarrhoea. Hepatoencephalopathy and ascites only occur with these symptoms in very advanced stages of chronic hepatitis. Only a part of the dogs have jaundice. Because of these aspecific symptoms, the diagnosis hepatitis is often not taken into consideration, even though the presence of a liver disease can be easily detected by measuring plasma concentrations of alkaline phosphatase and bile acids, one or both of which are elevated. The diagnosis is confirmed by histological examination of a liver biopsy sample. The most common forms of hepatitis are non-specific reactive hepatitis, acute hepatitis, and chronic hepatitis. Non-specific reactive hepatitis is a reaction against endotoxin as a result of sepsis or an increased gastrointestinal absorption. Treatment is directed to the primary process. Leptospirosis also causes non-specific reactive hepatitis, but then renal insufficiency is the most prominent feature. The diagnosis is made not on the basis of a liver biopsy but on the basis of increased IgM titres against Leptospira. Immediate treatment with antibiotics and infusions at the first signs (jaundice and uraemia) can save the animal's life. Acute hepatitis can develop as a result of infection, toxins, or liver hypoxia. There is no specific treatment, but adequate recovery often occurs with supportive treatment. Corticosteroids are contraindicated. Chronic hepatitis, which can lead to cirrhosis, is the most common form of hepatitis. It is an autoimmune inflammatory reaction that is usually caused by a virus infection but sometimes by poisoning (intoxication). Long treatment with prednisolone or azathioprine is usually successful, but early recognition of the disease increases the likelihood of success. Nowadays, chronic hepatitis due to hepatic copper accumulation in Beddlington terriers can be detected by DNA tests. Such tests make it possible to distinguish between carriers and non-carriers. Affected animals can be kept symptom-free by life-long treatment with zinc gluconate or penicillamine. PMID:9584348

Rothuizen, J; van den Ingh, T S

1998-04-15

332

Tamarix gallica ameliorates thioacetamide-induced hepatic oxidative stress and hyperproliferative response in Wistar rats.  

PubMed

Tamarix gallica, a hepatic stimulant and tonic, was examined for its ability to inhibit thioacetamide (TAA)-induced hepatic oxidative stress, toxicity and early tumor promotion response in male Wistar rats. TAA (6.6 mmol/kg body wt. i.p) enhanced lipid peroxidation, hydrogen peroxide content, glutathione S-transferase and xanthine oxidase with reduction in the activities of hepatic antioxidant enzymes viz., glutathione peroxidase, superoxide dismutase and caused depletion in the level of hepatic glutathione content. A marked increase in liver damage markers was also observed. TAA treatment also enhanced tumor promotion markers, ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with Tamarix gallica extract (25 and 50 mg/kg body weight) prevented TAA-promoted oxidative stress and toxicity. Prophylaxis with Tamarix gallica significantly reduced the susceptibility of the hepatic microsomal membrane for iron-ascorbate induced lipid peroxidation, H2O2 content, glutathione S-transferase and xanthine oxidase activities. There was also reversal of the elevated levels of liver marker parameters and tumor promotion markers. Our data suggests that Tamarix gallica is a potent chemopreventive agent and may suppress TAA-mediated hepatic oxidative stress, toxicity, and tumor promotion response in rats. PMID:16789436

Sehrawat, Anuradha; Sultana, Sarwat

2006-04-01

333

Percutaneous Management of a Hepatic Artery Aneurysm: Bleeding After Liver Transplantation  

SciTech Connect

In this article we present an unusual case of hepatic artery aneurysm bleeding due to a hepatic artery thrombosis after liver transplantation. The patient developed a recurrent hepatic artery thrombosis leading to severe graft failure in four consecutive liver transplantations. While being evaluated for a fifth transplant, stabilization of the clinical situation was attempted by interventional therapy. The first intervention was to place a stent into the hepatic artery to prevent further ischemic damage. This failed to improve graft function, but unfortunately led to the development of a pseudoaneurysm at the distal end with a subsequent rupture into the biliary tree. Bleeding was treated successfully by direct puncture and coil embolization of the aneurysm. In addition, the patient demonstrated a hemodynamically relevant portal vein stenosis on the CT scan. Stenting of the portal vein markedly improved graft function. After extensive investigations, a paroxysmal nocturnal hemoglobinuria was found to be the underlying cause of the recurrent hepatic artery thrombosis. Here we suggest that hepatic artery aneurysm bleeding is a rare but potentially fatal complication that can be successfully treated by percutaneous coil embolization. Additionally, we propose that stenting of the portal vein can lead to a significant improvement of the graft perfusion even though the hepatic artery remained occluded.

Millonig, Gunda; Graziadei, Ivo W. [University of Innsbruck, Department of Gastroenterology and Hepatology (Austria)], E-mail: ivo.graziadei@uibk.ac.at; Waldenberger, Peter [University of Innsbruck, Department of Radiology I (Austria); Koenigsrainer, Alfred [University of Innsbruck, Transplant Surgery (Austria); Jaschke, Werner [University of Innsbruck, Department of Radiology I (Austria); Vogel, Wolfgang [University of Innsbruck, Department of Gastroenterology and Hepatology (Austria)

2004-09-15

334

Three-Dimensional Imaging of Hepatic Sinusoids in Mice Using Synchrotron Radiation Micro-Computed Tomography  

PubMed Central

Hepatic sinusoid, the smallest vessel in the liver, plays important roles in hepatic microcirculation. Although the structure of the hepatic sinusoids affects diverse functions of the liver, little is known about morphological alterations in the sinusoids under pathological conditions. In this study, we show that the structure of hepatic sinusoids can be identified three-dimensionally in normal and carbon tetrachloride-injured mouse liver, using the absorption mode of synchrotron radiation micro-computed tomography. We observed that the hepatic sinusoidal structure on tomographic slice images was similar to that on histological images of normal and acutely injured mice. Moreover, centrilobular necrosis and structural alterations of the sinusoids in the necrotic region were detectable on tomographic slice and volume-rendered images of the acutely injured mice. Furthermore, quantitative analyses on 3D volume-rendered images of the injured sinusoid revealed decrease in the volume of the sinusoid and connectivity of the sinusoidal network. Our results suggest that the use of synchrotron radiation micro-computed tomography may improve our understanding of the pathogenesis of hepatic diseases by detecting the hepatic sinusoids and their alterations in three-dimensional structures of the damaged liver. PMID:23861925

Yoon, Yae Jin; Chang, Soeun; Kim, Oh Youn; Kang, Bo-Kyeong; Park, Jaesung; Lim, Jae-Hong; Yun Huang, Jung; Kim, Yoon-Keun; Byun, Jae Ho; Gho, Yong Song

2013-01-01

335

Iron overload facilitates hepatic fibrosis in the rat alcohol\\/low-dose carbon tetrachloride model  

Microsoft Academic Search

The role of iron deposition in initiating hepatic fibrosis in iron overload disorders is not clearly established, and it is becoming increasingly recognized that iron may be interacting with other potential liver-damaging agents. The authors therefore examined the interplay of iron and alcohol in rats administered subtoxic doses of carbon tetrachloride (CCL4) vapor at 20 ppm in customized chambers. At

Malcolm MacKinnon; Cindy Clayton; John Plummer; Michael Ahern; Patricia Cmielewski; Anthony Ilsley; Pauline Hall

1995-01-01

336

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

337

Chobert MN et al LIVER PRECURSOR CELLS INCREASE HEPATIC FIBROSIS INDUCED BY CHRONIC  

E-print Network

Chobert MN et al LIVER PRECURSOR CELLS INCREASE HEPATIC FIBROSIS INDUCED BY CHRONIC CARBON liver CCl4-induced fibrosis Pages of text: 27 Tables: 1 Black and white or grayscale figures: 1 Color complication of virtually all types of chronic liver damage, usually begins in portal areas, and its severity

Boyer, Edmond

338

Opioid receptor blockade reduces Fas-induced hepatitis in mice.  

PubMed

Fas (CD95)-induced hepatocyte apoptosis and cytotoxic activity of neutrophils infiltrating the injured liver are two major events leading to hepatitis. Because it has been reported that opioids, via a direct interaction, sensitize splenocytes to Fas-mediated apoptosis by upregulating Fas messenger RNA (mRNA) and modulated neutrophil activity, we assumed that opioids may participate in the pathophysiology of hepatitis. Using the hepatitis model induced by agonistic anti-Fas antibody in mice, we showed that opioid receptor blockade reduced liver damage and consequently increased the survival rate of animals when the antagonist naltrexone was injected simultaneously or prior to antibody administration. Treatment of mice with morphine enhanced mortality. Naloxone methiodide-a selective peripheral opioid antagonist-had a protective effect, but the absence of opioid receptors in the liver, together with lack of morphine effect in Fas-induced apoptosis of primary cultured hepatocytes, ruled out a direct effect of opioids on hepatocytes. In addition, the neutralization of opioid activity by naltrexone did not modify Fas mRNA expression in the liver as assessed with real-time quantitative polymerase chain reaction. Injured livers were infiltrated by neutrophils, but granulocyte-depleted mice were not protected against the enhancing apoptotic effect of morphine. In conclusion, opioid receptor blockade improves the resistance of mice to Fas-induced hepatitis via a peripheral mechanism that does not involve a down-modulation of Fas mRNA in hepatocytes nor a decrease in proinflammatory activity of neutrophils. PMID:15389866

Jaume, Martial; Jacquet, Sébastien; Cavaillès, Pierre; Macé, Gaëtane; Stephan, Lionel; Blanpied, Catherine; Demur, Cécile; Brousset, Pierre; Dietrich, Gilles

2004-11-01

339

Effects of hepatic arterial yttrium 90 glass microspheres in dogs.  

PubMed

A 22-micron glass microsphere called TheraSphere (Theragenics Corp., Atlanta, GA) has been developed in which yttrium 89 oxide is incorporated into the glass matrix and is activated by neutron bombardment to form the beta-emitting isotope yttrium 90 (Y 90) before using the spheres as radiotherapeutic vehicles. The injection of up to 12 times (on a liver weight basis) the anticipated human dose of nonradioactive TheraSphere into the hepatic arteries of dogs was well tolerated and produced clinically silent alterations within centrolobular areas. The hepatic arterial (HA) injection of radioactive TheraSphere also produced portal changes similar to those observed in humans after external beam therapy. While the extent of damage increased with the delivered dose, radiation exposures in excess of 30,000 cGy did not cause total hepatic necrosis and were compatible with survival. No microspheres distributed to the bone marrow and absolutely no myelosuppression was encountered in any animal. Proposed hepatic exposures to humans of 5000 to 10,000 cGy by means of these microspheres, therefore, would appear to be feasible and tolerable. Radiotherapeutic microsphere administration preceded by regional infusion of a radiosensitizing agent and/or immediately following the redistribution of blood flow toward intrahepatic tumor by vasoactive agents can potentially yield a synergistic, highly selective attack on tumors confined to the liver. PMID:3345490

Wollner, I; Knutsen, C; Smith, P; Prieskorn, D; Chrisp, C; Andrews, J; Juni, J; Warber, S; Klevering, J; Crudup, J

1988-04-01

340

Occult hepatitis B among Iranian hepatitis C patients  

PubMed Central

BACKGROUND: Occult hepatitis B is defined as presence of HBV DNA in tissue or serum without hepatitis B surface antigen. The aim of this study is to determine frequency of occult hepatitis B among hepatitis C patients in Tehran and compare the route of transmission and liver enzymes between positive and negative HBV DNA patients. METHODS: In a cross sectional study, serum of 103 hepatitis C cases (79.6% men and 20.4% women) were analyzed for s, x and core genes via a nested polymerase chain reaction technique. RESULTS: HBV DNA was detectable in serum of 20 patients (19.4%). No significant difference in age, sex and route of transmission were seen in HBV DNA positive and negative patients. In HBV DNA positive and negative groups, mean of AST was 73, 47 (p < 0.05) and mean of ALT was 76 and 36 respectively (p < 0.05). CONCLUSION: Occult hepatitis B was observed in a considerable number of hepatitis C patients in Tehran. It was associated with elevation in liver enzyme but was not related to route of transmission. PMID:21772856

Shavakhi, Ahmad; Norinayer, Babak; Esteghamat, Fateme Sadat; Seghatoleslami, Mohamad; Khodadustan, Mahsa; Somi, Mohamad Hosein; Masoodi, Mohsen; Zali, Mohamad Reza

2009-01-01

341

[Cholecystolithiasis as a cause of local hepatitis].  

PubMed

In an acute inflammation of gallbladder inflammatory process spreads on surrounding tissues, including hepatic tissue, what causes the regional hepatitis occurrence. In some patients, suffering calculous cholecystitis on background of transition of inflammatory process from gallbladder to hepatic tissue likewise a regional hepatitis, hyperbilirubinemia, the skin yellowness are revealed, what simulates choledocholithiasis and obturation jaundice. PMID:25417284

Dolimov, K S; Il'khamov, F A; Abdumazhidov, A Sh; Tukhtamuradov, Z Z; Dolimov, T K; Pivnitski?, I O

2014-08-01

342

Nilotinib counteracts thioacetamide-induced hepatic oxidative stress and attenuates liver fibrosis progression.  

PubMed

The aim of this study was to evaluate and compare the effects of imatinib and nilotinib to that of silymarin on established liver fibrosis and oxidative stress in a thioacetamide (TAA) rat model. Male Wistar rats received intraperitoneal (i.p.) injections of TAA (150mg/kg, twice weekly) for 12weeks. Daily treatments with imatinib (10mg/kg), nilotinib (10mg/kg), and silymarin (100mg/kg) were administered orally during the last 4weeks of TAA-administration. At the end of the study, hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis. Hepatic oxidative stress was assessed by measuring malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), total nitrate/nitrite (NOx), and reduced glutathione (GSH) contents, as well as myeloperoxidase (MPO) and superoxide dismutase (SOD) activities. Nilotinib, silymarin and, to a lesser extent, imatinib treatments ameliorated TAA-induced hepatic oxidative stress and damage as indicated by hepatic MDA, 4-HNE, NOx, GSH, MPO and SOD levels, as well as liver function tests. Hepatic histopathology results revealed that nilotinib, imatinib, and silymarin treatments decreased the mean score of fibrosis in TAA-treated rats by 24, 14, and 3%, respectively. However, nilotinib and silymarin, but not imatinib, treatments decreased hepatic collagen content in TAA-treated rats by 17 and 36%, respectively. In conclusion, we demonstrated for the first time that nilotinib not only protected against hepatic oxidative stress, but also slowed down liver fibrosis progression. Thus, we provide the first evidence that nilotinib might be a promising anti-fibrotic drug. PMID:20408881

Shaker, Mohamed E; Salem, Hatem A; Shiha, Gamal E; Ibrahim, Tarek M

2011-04-01

343

Inhibitor of nuclear factor-Kappa B activation attenuates venular constriction, leukocyte rolling-adhesion and microvessel rupture induced by ethanol in intact rat brain microcirculation: relation to ethanol-induced brain injury  

Microsoft Academic Search

The present study was designed to test the hypothesis that acute, local administration of a specific inhibitor of nuclear factor-Kappa B activation (which prevents rapid proteolysis of IKB-?) will attenuate cerebral (cortical) venular constrictions, leukocyte-endothelial wall interactions and postcapillary damage induced by medium to high concentrations of ethanol in the intact rat brain. Perivascular or i.p. administration of ethanol (100,

Burton M Altura; Asefa Gebrewold

2002-01-01

344

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

345

CHEMOKINES IN THE IMMUNOPATHOGENESIS OF HEPATITIS C INFECTION  

PubMed Central

Chronic infection with the hepatitis C virus (HCV), a noncytopathic hepatotropic RNA virus, affects over 170 million people worldwide1,2. In the majority of cases neither the early innate nor the later adaptive immune response succeeds in clearing the virus and infection becomes chronic1. Furthermore, in many patients the ineffective inflammatory response drives fibrogenesis and the development of cirrhosis3. It is critical to understand this immune pathology if preventative and curative therapies are to be developed. Chemokines are a superfamily of small proteins that promote leukocyte migration and orchestrate the immune response to viruses including HCV4. Chemokines are crucial for viral elimination but inappropriate persistence of expression in chronic hepatitis C infection can drive tissue damage and inflammation5. Here we review the role of chemokines and their receptors in HCV. PMID:19177577

Heydtmann, Mathis; Adams, David H.

2010-01-01

346

Chronic hepatitis B virus infection in Asian countries.  

PubMed

Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC. PMID:11197043

Merican, I; Guan, R; Amarapuka, D; Alexander, M J; Chutaputti, A; Chien, R N; Hasnian, S S; Leung, N; Lesmana, L; Phiet, P H; Sjalfoellah Noer, H M; Sollano, J; Sun, H S; Xu, D Z

2000-12-01

347

Hepatitis B vaccination.  

PubMed

Hepatitis B virus is a worldwide leading cause of acute and chronic liver disease including cirrhosis and hepatocellular carcinoma. Effective vaccines have been available since the early '80s and vaccination has proved highly successful in reducing the disease burden, the development of the carrier state and the HB-related morbidity and mortality in the countries where vaccination has been implemented.   Neutralizing (protective) antibodies (anti-HBs) induced by vaccination are targeted largely towards the amino acid hydrophilic region, referred to as the common a determinant which is present on the outer protein coat or surface antigen (HBsAg), spanning amino acids 124-149. This provides protection against all HBV genotypes (from A to H) and is responsible for the broad immunity afforded by hepatitis B vaccination. Thus, alterations of residues within this region of the surface antigen may determine conformational changes that can allow replication of the mutated HBV in vaccinated people. An important mutation in the surface antigen region was identified in Italy some 25 years ago in infants born to HBsAg carrier mothers who developed breakthrough infections despite having received HBIG and vaccine at birth. This virus had a point mutation from guanosine to adenosine at nucleotide position 587, resulting in aa substitution from glycine (G) to arginine (R) at position 145 in the a determinant. Since the G145R substitution alters the projecting loop (aa 139-147) of the a determinant, the neutralizing antibodies induced by vaccination are no longer able to recognize the mutated epitope. Beside G145R, other S-gene mutations potentially able to evade neutralizing anti-HBs and infect vaccinated people have been described worldwide. In addition, the emergence of Pol mutants associated with resistance to treatment with nucleos(t)ide analogues can select viruses with crucial changes in the overlapping S-gene, potentially able to alter the S protein immunoreactivity. Thus such mutants have the potential to infect both naïve and immunized people, negatively affecting the efficacy of both the antiviral treatment and the vaccination programs. Despite concern, at present the overall impact of vaccine escapes mutants seems to be low and they do not pose a public health threat or a need to modify the established hepatitis B vaccination programs. The development of novel NAs with a high barrier to resistance is warranted. PMID:25483515

Romanò, Luisa; Paladini, Sara; Galli, Cristina; Raimondo, Giovanni; Pollicino, Teresa; Zanetti, Alessandro R

2014-08-01

348

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

349

Transfusion-transmitted virus in association with hepatitis A-E viral infections in various forms of liver diseases in India  

PubMed Central

AIM: To describe the prevalence of transfusion-transmitted virus (TTV) infection in association with hepatitis A-E viral infections in different forms of liver diseases in North India. METHODS: Sera from a total number of 137 patients, including 37 patients with acute viral hepatitis (AVH), 37 patients with chronic viral hepatitis (CVH), 31 patients with cirrhosis of liver and 32 patients with fulminant hepatic failure (FHF), were analyzed both for TTV-DNA and hepatitis A-E viral markers. Presence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis E virus (HEV) infections was detected in different proportions in different groups. Moreover, TTV-DNA was simultaneously tested in 100 healthy blood donors also. RESULTS: None of the patients had hepatitis A virus (HAV) and hepatitis D virus (HDV) infections. Overall prevalence of TTV-DNA was detected in 27.1% cases with AVH, 18.9% cases with CVH, 48.4% cases with cirrhosis and 9.4% cases with FHF. TTV-DNA simultaneously tested in 100 healthy blood donors showed 27% positivity. On establishing a relation between TTV infection with other hepatitis viral infections, TTV demonstrated co-infection with HBV, HCV and HEV in these disease groups. Correlation of TTV with ALT level in sera did not demonstrate high ALT level in TTV-infected patients, suggesting that TTV does not cause severe liver damage. CONCLUSION: TTV infection is prevalent both in patients and healthy individuals in India. However, it does not have any significant correlation with other hepatitis viral infections, nor does it produce an evidence of severe liver damage in patients with liver diseases. PMID:16688839

Irshad, M; Sharma, Y; Dhar, I; Singh, J; Joshi, YK

2006-01-01

350

[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

351

Diabetes and Hepatitis B Vaccination  

MedlinePLUS

... for hepatitis B if they share blood glucose meters, fingerstick devices or other diabetes-care equipment such ... to have occurred from: • Use of blood glucose meter for more than one resident without cleaning and ...

352

Hepatitis viruses and liver transplantation.  

PubMed

Acute and chronic liver diseases related to hepatitis viruses are the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. The risk of viral B reinfection is: 80% in the absence of prophylaxis; is related to the presence of active viral B replication prior to transplantation; is higher in patients with chronic liver disease, rather than with fulminant hepatitis; and is higher in patients with hepatitis B virus (HBV)-related liver disease alone rather than in those with HBV-hepatitis delta virus (HDV) infection. Post-transplant long-term passive antibody to hepatitis B (anti-HB) immunoprophylaxis reduces the risk of HBV recurrence to 30% in patients with HBV cirrhosis, and to less than 10% in those with fulminant hepatitis B. Patients with HBV-HDV liver disease receiving passive anti-HB immunoprophylaxis are at low risk of HBV recurrence (10-15%), but at high risk of HDV recurrence (80%). However, HDV reinfection of the graft has no clinicopathological consequence in the absence of concomitant HBV reinfection. The five year survival of patients transplanted for HBV cirrhosis and for HDV cirrhosis at the Hepatobiliary Center, Hôpital Paul Brousse is 72% and 85%, respectively. Hepatitis B virus reinfection of the graft is characterized by a high level of viral replication, and a chronic outcome. Antiviral treatments such as ganciclovir, adenine arabinoside monophosphate, famcyclovir, and lamivudine have a place after transplantation and may stop HBV replication, ganciclovir, famcyclovir and lamivudine should be continued for several months and in some cases indefinitely. Hepatitis C virus reinfection is almost constant, assessed by the persistence of hepatitis C virus (HCV)-RNA in the serum in 90% of cases. Acute lobular hepatitis appeared in 75% of patients at a median of 4 months post transplantation with a range of between 23 days and 4 years. In our series, the 5 year actuarial rate of HCV acute hepatitis on the graft, chronic hepatitis, and cirrhosis, is 75, 60, and 8%, respectively. Hepatitis C virus RNA level is dramatically increased after transplantation and seems to correlate with the occurrence of acute hepatitis on the graft. A positive relation between genotype 1b and prevalence and severity of HCV hepatitis on the graft have been suggested in European series. There is no demonstrated way to prevent HCV reinfection. The use of interferon for the treatment of HCV hepatitis on the graft was disappointing due to a poor antiviral effect and the occurrence of chronic rejection episodes in some patients. Promising results of the combination of interferon and ribavirine have been reported and need confirmation. The 5 year survival of patients transplanted for viral C cirrhosis at the Hepatobiliary Center, Hôpital Paul Brousse is 78%. In conclusion, patients with HBV cirrhosis and without HBV replication are candidates for liver transplantation. Long-term passive anti-HB prophylaxis is the best way to prevent HBV recurrence. Patients with HBV replication should be included in protocols using combinations of antiviral treatments and passive anti-HB immunoprophylaxis. Viral C reinfection is frequent, but medium-term survival is good. However, long-term graft and patient survival remains unknown and methods to prevent and treat HCV reinfection on the graft are needed. PMID:9407355

Samuel, D; Feray, C; Bismuth, H

1997-10-01

353

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

354

CHARACTERIZATION OF DAMAGED MATERIALS  

SciTech Connect

Thermal damage experiments were conducted on LX-04, LX-10, and LX-17 at high temperatures. Both pristine and damaged samples were characterized for their material properties. A pycnometer was used to determine sample true density and porosity. Gas permeability was measured in a newly procured system (diffusion permeameter). Burn rate was measured in the LLNL strand burner. Weight losses upon thermal exposure were insignificant. Damaged pressed parts expanded, resulting in a reduction of bulk density by up to 10%. Both gas permeabilities and burn rates of the damaged samples increased by several orders of magnitude due to higher porosity and lower density. Moduli of the damaged materials decreased significantly, an indication that the materials became weaker mechanically. Damaged materials were more sensitive to shock initiation at high temperatures. No significant sensitization was observed when the damaged samples were tested at room temperature.

Hsu, P C; Dehaven, M; McClelland, M; Chidester, S; Maienschein, J L

2006-06-23

355

Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation  

PubMed Central

Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFk? pathway (I?B?) by TNF-? was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-? blockage by anti-TNF-? in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-?). PMID:25197426

Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

2014-01-01

356

Protective action of fenugreek (Trigonella foenum graecum) seed polyphenols against alcohol-induced protein and lipid damage in rat liver.  

PubMed

The study investigates the effect of fenugreek seed polyphenol extract (FPEt) on ethanol-induced damage in rat liver. Chronic ethanol administration (6 g kg(-1) day(-1) x 60 days) caused liver damage that was manifested by excessive formation of thiobarbituric-acid-reactive substances, lipid hydroperoxides, and conjugated dienes, the end products of lipid peroxidation, and significant elevation of protein carbonyl groups and diminution of sulfhydryl groups, a marker of protein oxidation. Decreased activities of enzymic and non-enzymic antioxidant levels and decreased levels of thiol groups (both non-protein and protein) were observed in ethanol-treated rats. Further, ethanol significantly increased the accumulation of 4-hydroxynonenal protein adducts, nitrated and oxidized proteins in liver which was evidenced by immunohistochemistry. Administration of FPEt to ethanol-fed rats (200 mg kg(-1) day(-1)) significantly reduced the levels of lipid peroxidation products and protein carbonyl content, increased the activities of antioxidant enzymes, and restored the levels of thiol groups. The effects of FPEt were comparable with those of a positive control, silymarin. These findings show that FPEt ameliorates the pathological liver changes induced by chronic ethanol feeding. PMID:18240000

Kaviarasan, S; Sundarapandiyan, R; Anuradha, C V

2008-10-01

357

Phosphoinositide 3-kinase ?/? inhibition does not prevent concanavalin A-induced hepatitis.  

PubMed

An increasing number of studies have suggested that phosphoinositide 3-kinase-? (PI3K?) and PI3K? are involved in the pathogenesis of autoimmune and inflammatory diseases, such as asthma and atherosclerosis. However, the underlying mechanism of acute hepatitis remains unknown. The present study aimed to determine the effect of PI3K?/? inhibition on hepatic injury in a murine model of hepatitis induced by concanavalin A (ConA). It was demonstrated that the pharmacological inhibition of PI3K?/? by TG100-115 did not prevent liver damage following ConA challenge. Furthermore, the PI3K?/? inhibition resulted in elevated transaminase activity in the serum, aggravated hepatic lesions characterized by hepatic necrosis, increased inflammatory cell infiltration and apoptosis of hepatocytes. Survival tests demonstrated that TG100-115 significantly increased the death rate of mice following ConA challenge. In addition, TG100-115 increased the serum levels of the proinflammatory cytokine IL-2 following ConA injection. These results may oppose the development of PI3K?/? inhibitors as therapeutic agents, particularly for the treatment of human hepatitis. PMID:23969545

Liu, Yuanyuan; Xiong, Li; Chang, Ying; Tang, Jianying; Ang, Wei; Yang, Tao; Pi, Weiyi; Yang, Xiaoyan; Ye, Weiwei; Luo, Youfu; Wang, Zhenling

2013-11-01

358

Tamoxifen prevents induction of hepatic neoplasia by zeranol, an estrogenic food contaminant.  

PubMed Central

Zeranol (alpha-zearalanol) is a beta-resorcylic acid lactone (RAL) that has estrogen activity. It is synthesized by molds and is difficult to avoid in human food products. We tested the ability of this mycoestrogen to damage the liver of the Armenian hamster, a rodent that is especially sensitive to hepatotoxic effects of exogenous estrogens. Zeranol induced acute hepatotoxicity and, subsequently, hepatic carcinogenesis; both effects were blocked by tamoxifen, suggesting estrogen receptor mediation. Because zeranol is acting alone as a primary initiator of hepatic neoplasms, this model provides an unusual opportunity to study the pathogenesis of estrogen-initiated tumorigenesis. PMID:1736291

Coe, J E; Ishak, K G; Ward, J M; Ross, M J

1992-01-01

359

Regulation of hepatic growth.  

PubMed

The liver is a conditional renewal system, which in the adult organism undergoes minimal cell production and/or cell renewal. However, a reduction in liver cell mass, because of either actual cell loss or cell atrophy, evokes a rapid regenerative response tailored to replace the lost tissue. Synthesis of DNA begins as early as 15 h after a two-thirds hepatectomy, and the fact that all the remaining hepatocytes enter DNA synthesis within the next 48 h does indicate they are all potentially proliferative, and it is unlikely that a distinct stem cell compartment exists. The temporal sequelae of events can be best explained by the semisynchronous passage of cells from G0 into the proliferative cycle (see Fig. 2) where they undergo one or more rounds of cell division before decycling back into the proliferatively quiescent G0 state. The age of the animal and its nutritional and hormonal status are all important modifiers of the response, but none of them is critical to the regenerative process. Experiments involving the administration of sera or the transfer of blood between animals strongly favor the existence of humoral regulatory factors; the liver is apparently capable of producing both inhibitory and stimulatory molecules that act by negative and positive feedback mechanisms, respectively, to control tissue homeostasis, whereas other organs, notably the pancreas, are important sources of facilitatory molecules. A chemical mechanism of self inhibition is a very intellectually appealing hypothesis, but at present there is no consistent message as to the identity of the inhibitory molecule, although most studies suggest the target site for its action is the G1-S transition. Unless the whole field is one of multilateral analysis of an artifact, then endogenous growth inhibitors do exist, but the problem now is one of biochemical isolation and characterization. The field compares rather badly with the many success stories in recent years in which new hormones and peptides have been speedily isolated and purified. A reduction in liver size appears to be associated with a decrease in the concentration of an hepatic growth inhibitor and the production and/or unmasking of a stimulatory factor(s) that is also of hepatic origin. Once again, there is little information about the biochemical nature of the principle and much less on its mode of action. We all assume that such stimulators, and for that matter inhibitors as well, act on "restriction points" or "mitosis operons" and so on.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2426724

Alison, M R

1986-07-01

360

Occult hepatitis B virus infection  

PubMed Central

Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of HBV DNA in the absence of detectable hepatitis B surface antigen. Since OBI was first described in the late 1970s, there has been increasing interest in this topic. The prevalence of OBI varies according to the different endemicity of HBV infection, cohort characteristics, and sensitivity and specificity of the methods used for detection. Although the exact mechanism of OBI has not been proved, intra-hepatic persistence of viral covalently closed circular DNA under the host’s strong immune suppression of HBV replication and gene expression seems to be a cause. OBI has important clinical significance in several conditions. First, OBI can be transmitted through transfusion, organ transplantation including orthotopic liver transplantation, or hemodialysis. Donor screening before blood transfusion, prophylaxis for high-risk organ transplantation recipients, and dialysis-specific infection-control programs should be considered to reduce the risk of transmission. Second, OBI may reactivate and cause acute hepatitis in immunocompromised patients or those receiving chemotherapy. Close HBV DNA monitoring and timely antiviral treatment can prevent HBV reactivation and consequent clinical deterioration. Third, OBI may contribute to the progression of hepatic fibrosis in patients with chronic liver disease including hepatitis C. Finally, OBI seems to be a risk factor for hepatocellular carcinoma by its direct proto-oncogenic effect and by indirectly causing persistent hepatic inflammation and fibrosis. However, this needs further investigation. We review published reports in the literature to gain an overview of the status of OBI and emphasize the clinical importance of OBI. PMID:25544873

Kwak, Min-Sun; Kim, Yoon Jun

2014-01-01

361

Optical damage in KTN  

Microsoft Academic Search

An analysis of light-induced refractive-index changes (``optical damage'') has been carried out for paraelectric electro-optic crystals. The results are compared with experimental data taken on several KTN crystals. Both the spatial extent and temporal variations of optical damage are accurately determined by the theory for all crystals tested. The rate at which optical damage occurs can be used to determine

S. R. King; T. S. Hartwick; A. B. Chase

1972-01-01

362

How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus  

E-print Network

How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus Maria Xiridou1 *, Barbara Borkent) virus is a defective virus that relies on hepatitis B virus (HBV) for transmission; infection of the bond between the two viruses, control measures for HBV may have also affected the spread of hepatitis D

Hulshof, Joost

363

Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.  

PubMed

Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. PMID:21896699

Tohme, Rania A; Drobeniuc, Jan; Sanchez, Roger; Heseltine, Gary; Alsip, Bryan; Kamili, Saleem; Hu, Dale J; Guerra, Fernando; Teshale, Eyasu H

2011-10-01

364

Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV  

Microsoft Academic Search

OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers

J Tor; J M Llibre; M Carbonell; R Muga; A Ribera; V Soriano; B Clotet; M Sabriá; M Foz

1990-01-01

365

A Virus Similar to Human Hepatitis B Virus Associated with Hepatitis and Hepatoma in Woodchucks  

Microsoft Academic Search

Particles with properties similar to those associated with human hepatitis B were found in serum from woodchucks with chronic hepatitis and hepatocellular carcinoma. It is suggested that woodchuck hepatitis virus is a second member of a novel class of viruses represented by the human hepatitis B virus.

Jesse Summers; Jo Marie Smolec; Robert Snyder

1978-01-01

366

HIGH PREVALENCE OF HEPATITIS B VIRUS AND HEPATITIS D VIRUS IN THE WESTERN BRAZILIAN AMAZON  

Microsoft Academic Search

Severe cases of hepatitis caused by hepatitis B virus (HBV) or hepatitis D virus (HDV) are often seen in the Brazilian Amazon, but there is a paucity of epidemiologic studies on viral hepatitis in this area. Thus, a cross- sectional study to investigate the prevalence of markers for HBV and HDV was performed. Serum samples were collected after participants completed

SEBASTIAO VIANA; RAYMUNDO PARANA; REGINA CELIA MOREIRA; ADRIANA PARISE COMPRI; VANISE MACEDO

2005-01-01

367

HEPATITIS B VACCINE DECLARATION FORM Please submit this completed Hepatitis B Vaccine Form to  

E-print Network

HEPATITIS B VACCINE DECLARATION FORM Please submit this completed Hepatitis B Vaccine Form select and complete one of the applicable sections below: I. "I WOULD LIKE TO RECEIVE THE HEPATITIS B THE HEPATITIS B VACCINE" "I understand that due to my occupational exposure to blood or other potentially

368

Hepatitis C treatment & management.  

PubMed

Combination therapy with pegylated interferon alfa (PEG-IFN alfa) and the nucleoside analogue ribavirin is the current standard of care in patients infected with hepatitis C virus (HCV). Patients with HCV genotype 1 have a much less favorable response to therapy and are treated for 12 months, compared with patients infected with genotypes 2 and 3, in whom a 6-month course of therapy is sufficient. If viremia is present after 6 months, additional therapy has a negligible benefit, and treatment should be stopped in all patients regardless of the viral genotype. With HIV coinfection, all patients with a response to therapy at the end of 6 months should receive an additional 6 months of combination therapy regardless of the genotype. Patients with acute HCV infection should be treated for 6 months. The addition of protease inhibitors to the combination of PEG-IFN alfa and ribavirin is becoming the new standard of care for the treatment of chronic HCV infection. Regimens that include a protease inhibitor significantly improve sustained virologic response rates in patients with genotype 1 HCV infection. PMID:24653754

Andronescu, D; Diaconu, S; Tiuca, N; Purcarea, R M; Andronescu, C I

2014-03-15

369

Hepatitis C Treatment & Management  

PubMed Central

Abstract Combination therapy with pegylated interferon alfa (PEG-IFN alfa) and the nucleoside analogue ribavirin is the current standard of care in patients infected with hepatitis C virus (HCV). Patients with HCV genotype 1 have a much less favorable response to therapy and are treated for 12 months, compared with patients infected with genotypes 2 and 3, in whom a 6-month course of therapy is sufficient. If viremia is present after 6 months, additional therapy has a negligible benefit, and treatment should be stopped in all patients regardless of the viral genotype. With HIV coinfection, all patients with a response to therapy at the end of 6 months should receive an additional 6 months of combination therapy regardless of the genotype. Patients with acute HCV infection should be treated for 6 months. The addition of protease inhibitors to the combination of PEG-IFN alfa and ribavirin is becoming the new standard of care for the treatment of chronic HCV infection. Regimens that include a protease inhibitor significantly improve sustained virologic response rates in patients with genotype 1 HCV infection. PMID:24653754

Andronescu, D; Diaconu, S; Tiuca, N; Purcarea, RM; Andronescu, CI

2014-01-01

370

Damage Tolerance of Composites  

NASA Technical Reports Server (NTRS)

Fracture control requirements have been developed to address damage tolerance of composites for manned space flight hardware. The requirements provide the framework for critical and noncritical hardware assessment and testing. The need for damage threat assessments, impact damage protection plans, and nondestructive evaluation are also addressed. Hardware intended to be damage tolerant have extensive coupon, sub-element, and full-scale testing requirements in-line with the Building Block Approach concept from the MIL-HDBK-17, Department of Defense Composite Materials Handbook.

Hodge, Andy

2007-01-01

371

Evaluation of hepatic subcellular fractions for Alamar blue and MTT reductase activity.  

PubMed

Alamar blue and MTT are indicators used to measure cytotoxicity of various chemicals in cultured cells. Both Alamar blue and MTT are reduced by mitochondrial enzymes. We observed enhanced fluorescence of Alamar blue when kidney epithelial cells were co-incubated with hepatic post-mitochondrial supernatant (S9) fractions as compared with cells incubated in the absence of S9 fractions. The present studies were carried out to determine whether hepatic cytosolic and/or microsomal enzymes were capable of metabolizing Alamar blue and/or MTT to their reduced products. Livers from female Sprague-Dawley rats were used to prepare S9 fraction, and mitochondrial, microsomal and cytosolic fractions. Fractions containing 1 or 5 mg protein/ml were incubated with Alamar blue or MTT for up to 4 h. Fluorescence (Alamar blue) or absorbance (MTT) were determined and expressed as differences between treated wells and controls. Hepatic fractions (S9, mitochondria, microsomes and cytosol) caused concentration- and time-dependent increases in Alamar blue fluorescence and MTT absorbance. Reduction of Alamar blue and MTT by hepatic S9 fraction was abolished by heating. Reduction of Alamar blue by hepatic mitochondria was approximately equivalent to that catalyzed by hepatic S9 fraction or cytosol. Reduction of MTT by hepatic mitochondria was approximately equivalent to that catalyzed by hepatic S9 fraction or microsomes. These data indicate that mitochondrial, cytosolic and microsomal enzymes reduce Alamar blue and MTT. Therefore, caution should be exercised in ascribing decreases in viability as due solely to mitochondrial damage when using either of these dyes. PMID:11377098

Gonzalez, R J; Tarloff, J B

2001-06-01

372

Ontogeny of rat hepatic adrenoceptors  

SciTech Connect

Hepatic alpha-1, alpha-2 and beta-2 adrenoceptors were characterized during development of the rat through Scatchard analysis of (3H)prazosin, (3H)rauwolscine and (125I)pindolol binding to liver membrane preparations. Major changes in adrenoceptor numbers occur shortly before birth at weaning. The fetal rat liver is characterized by a large number of alpha-2 adrenoceptors, which falls 10-fold by birth. The number of hepatic beta-2 adrenoceptors decreases gradually during development, and is lower at all times than the number of alpha-1 and alpha-2 adrenoceptors. The developmental profile of the hepatic alpha-1 adrenoceptor is biphasic: there is a 2 to 3-fold fall in alpha-1 adrenoceptor number at birth and a 3- to 5-fold rise at weaning. While absolute numbers of alpha-1 and beta-2 adrenoceptors do not correlate precisely with reported actions of epinephrine and norepinephrine on hepatic metabolism during ontogeny, the increasing ratio of alpha-1/beta-2 hepatic adrenoceptors may contribute to the conversion from predominantly beta effects of catecholamines reported in fetal and suckling rat liver to the predominantly alpha-1 effects that are well documented in the adult male rat.

McMillian, M.K.; Schanberg, S.M.; Kuhn, C.M.

1983-10-01

373

Parvovirus B19 Associated Hepatitis  

PubMed Central

Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; liver manifestations and hepatitis are examples of them. Parvovirus B19 hepatitis associated aplastic anemia and its coinfection with other hepatotropic viruses are relatively underrecognized, and there is sufficient evidence in the literature suggesting that B19 infections can cause a spectrum of liver diseases from elevation of transaminases to acute hepatitis to fulminant liver failure and even chronic hepatitis. It can also cause fatal macrophage activation syndrome and fibrosing cholestatic hepatitis. Parvovirus B19 is an erythrovirus that can only be replicate in pronormoblasts and hepatocytes, and other cells which have globosides and glycosphingolipids in their membrane can also be affected by direct virus injury due to nonstructural protein 1 persistence and indirectly by immune mediated injury. The virus infection is suspected in bone marrow aspiration in cases with sudden drop of hemoglobin and onset of transient aplastic anemia in immunosuppressed or immunocompetent patients and is confirmed either by IgM and IgG positive serology, PCR analysis, and in situ hybridization in biopsy specimens or by application of both. There is no specific treatment for parvovirus B19 related liver diseases, but triple therapy regimen may be effective consisting of immunoglobulin, dehydrohydrocortisone, and cyclosporine. PMID:24232179

Bihari, Chhagan; Rastogi, Archana; Saxena, Priyanka; Rangegowda, Devraj; Chowdhury, Ashok; Gupta, Nalini; Sarin, Shiv Kumar

2013-01-01

374

Hepatitis B surface antigen in late hepatitis B infection.  

PubMed

Hepatitis B surface antigen (HBsAg) levels are used to evaluate and monitor clinical phases of chronic hepatitis B infection but their clinical significance is unclear in the late complications, cirrhosis of the liver and hepatocellular carcinoma. This study aimed to evaluate HBsAg levels across the whole natural history of hepatitis B virus infection, including late complications. This retrospective, cross-sectional study enrolled 838 treatment-naive patients diagnosed with chronic hepatitis B infection at First Affiliated Hospital of Fujian Medical University between 2009 and 2012. Patients were classified into six groups: immunotolerance, immunoclearance, low replicative, negative hepatitis e (HBeAg) phases, liver cirrhosis, and hepatocellular carcinoma. Main outcome measures were serum HBsAg, HBeAg, HBV DNA, total bilirubin, albumin, alanine and aspartate aminotransferase, and quantitative correlation of HBsAg with HBV DNA. HBsAg levels declined significantly between clinical phases of infection (all P?hepatitis B infection phases, decreasing progressively from chronic infection to cirrhosis and hepatocellular carcinoma. Significant correlations are found between serum HBsAg and HBV DNA. J. Med. Virol. 87:380-387, 2015. © 2014 Wiley Periodicals, Inc. PMID:25604455

Zeng, Da-Wu; Zhu, Yue-Yong; Huang, Qian; Zhang, Jie-Min; Wu, Yin-Lian; Dong, Jing; Jiang, Jia-Ji; Liu, Yu-Rui

2015-03-01

375

Hepatitis B Precore Protein: Pathogenic Potential and Therapeutic Promise  

PubMed Central

Hepatitis B virus (HBV), a small and economically packaged double-stranded DNA virus, represents an enormous global health care burden. In spite of an effective vaccine, HBV is endemic in many countries. Chronic hepatitis B (CHB) results in the development of significant clinical outcomes such as liver disease and hepatocellular carcinoma (HCC), which are associated with high mortality rates. HBV is a non-cytopathic virus, with the host's immune response responsible for the associated liver damage. Indeed, HBV appears to be a master of manipulating and modulating the immune response to achieve persistent and chronic infection. The HBV precore protein or hepatitis B e antigen (HBeAg) is a key viral protein involved in these processes, for instance though the down-regulation of the innate immune response. The development of new therapies that target viral proteins, such as HBeAg, which regulates of the immune system, may offer a new wave of potential therapeutics to circumvent progression to CHB and liver disease. PMID:22869468

Locarnini, Stephen

2012-01-01

376

Hepatitis GB virus-C\\/hepatitis G virus infection in liver disease  

Microsoft Academic Search

Hepatitis GB virus-C (HGBV-C)\\/hepatitis G virus (HGV) infection was investigated in 106 children with liver disease (54 boys and 52 girls, mean age 7.3 years); 12 with chronic hepatitis C virus infection, 29 with positive hepatitis B surface antigen, nine with idiopathic fulminant hepatic failure, seven with graft dysfunction after liver transplantation associated with autoimmune features, 20 with cryptogenic liver

Ikuo Nagata; Nikos Tzampouras; Shilpa Chokshi; Nikolai V Naoumov; Paul Cheeseman; Heather M Smith; Alastair J Baker; Roger Williams; Giorgina Mieli-Vergani

1997-01-01

377

Hepatic toxicity resulting from cancer treatment  

Microsoft Academic Search

Radiation-induced liver disease (RILD), often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites approximately 2 weeks to 4 months after hepatic irradiation. There has been a renewed interest in hepatic irradiation because of two significant advances in cancer treatment: three dimensional radiation therapy treatment planning and bone marrow transplantation using total body irradiation. RILD resulting

Theodore S. Lawrence; John M. Robertson; Mitchell S. Anscher; Randy L. Jirtle; William D. Ensminger; Luis F. Fajardo

1995-01-01

378

77 FR 45895 - World Hepatitis Day, 2012  

Federal Register 2010, 2011, 2012, 2013

...Proclamation 8845 of July 27, 2012 World Hepatitis Day, 2012 By the President of the United...in twelve people is living with viral hepatitis--a disease that threatens the health...of their infection status. On World Hepatitis Day, we call attention to this...

2012-08-02

379

76 FR 46181 - World Hepatitis Day, 2011  

Federal Register 2010, 2011, 2012, 2013

...Proclamation 8696--World Hepatitis Day, 2011 Presidential Documents Federal...Proclamation 8696 of July 27, 2011 World Hepatitis Day, 2011 By the President of the United...millions of Americans are living with viral hepatitis. As many as three-fourths of...

2011-08-01

380

Ischemia-Reperfusion Damage  

PubMed Central

Ischemia-reperfusion damage is a complex pathological process that begins with tissue anoxia and continues with the production of free oxygen radicals, expanding with the inflammatory response. The literature suggests the importance of antioxidant and anti-inflammatory treatment to treat ischemia-reperfusion-related tissue damage.

Yapca, Omer E.; Borekci, Bunyamin; Suleyman, Halis

2013-01-01

381

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

PubMed

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to <1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 ?g/g in the lungs of ethanol-fed mice as compared to 1.5 ?g/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1? and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. PMID:24625836

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

2014-06-01

382

Hepatitis C, stigma and cure  

PubMed Central

The infection with hepatitis C virus (HCV) is one of the most important global chronic viral infections worldwide. It is estimated to affect around 3% of the world population, about 170-200 million people. Great part of the infections are asymptomatic, the patient can be a chronic carrier for decades without knowing it. The most severe consequences of the chronic infection are liver cirrhosis and hepatocellular carcinoma, which appears in 20%-40% of the patients, leading to hepatic failure and death. The HCV was discovered 25 years ago in 1989, is a RNA virus and classified by the World Health Organization as an oncogenic one. Hepatocellular carcinoma is one of the most important cancers, the fifth worldwide in terms of mortality. It has been increasing in the Ocidental world, mainly due to chronic hepatitis C. Hepatitis C is not only a liver disease and a cause of cirrhosis, but also a mental, psychological, familiar, and social disease. The stigma that the infected person sometimes carries is tremendous having multiple consequences. The main cause is lack of adequate information, even in the health professionals setting. But, besides the “drama” of being infected, health professionals, family, society and the infected patients, must be aware of the chance of real cure and total and definitive elimination of the virus. The treatment for hepatitis C has begun in the last 80´s with a percentage of cure of 6%. Step by step the efficacy of the therapy for hepatitis C is rapidly increasing and nowadays with the very new medications, the so called Direct Antiviral Agents-DAAs of new generation, is around 80%-90%. PMID:24187444

Marinho, Rui Tato; Barreira, David Pires

2013-01-01

383

Hepatitis C and liver transplantation  

NASA Astrophysics Data System (ADS)

Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

Brown, Robert S.

2005-08-01

384

Chronic hepatitis B in hepatocarcinogenesis  

PubMed Central

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and has a wide geographical variation. Eighty per cent of HCC is attributed to hepatitis B virus (HBV). The predominant carcinogenic mechanism of HBV associated HCC is through the process of liver cirrhosis, but direct oncogenic effects of HBV may also contribute. Prevention of HBV infections as well as effective treatment of chronic hepatitis B is still needed for the global control of HBV associated HCC. Continued investigation of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in the liver. PMID:16891440

Park, N H; Song, I H; Chung, Y?H

2006-01-01

385

Effect of Helicteres isora bark extract on blood glucose and hepatic enzymes in experimental diabetes.  

PubMed

The effect of oral administration of an aqueous extract of the bark of Helicteres isora was investigated on blood glucose and plasma antioxidant status in streptozotocin (STZ) induced diabetic rats. The study was also undertaken to evaluate the role of hepatic enzymes in experimental diabetes. Oral administration of a bark extract of Helicteres isora (100, 200 mg/kg) in STZ diabetic rats caused a significant increase in body weight, hepatic hexokinase activity and significant decrease in hepatic glucose-6-phosphatase, serum acid phosphatase (ACP), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Based on these findings, we suggest that Helicteres isora possesses hypoglycemic and hepatoprotective activity and is able to ameliorate biochemical damage in STZ induced diabetic rats. PMID:16649554

Kumar, G; Murugesan, A G; Rajasekara Pandian, M

2006-04-01

386

Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat  

Microsoft Academic Search

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and

Eduardo Fernández-Martínez; Víctor Pérez-Álvarez; Victor Tsutsumi; Mineko Shibayama; Pablo Muriel

2006-01-01

387

Occult Hepatitis C Virus Infection in Patients With Autoimmune Hepatitis  

PubMed Central

Background: Occult hepatitis C virus infection (OCI) is recognized by finding hepatitis C virus (HCV) RNA in hepatocytes without detectable anti-HCV antibodies and viral RNA in plasma. Autoimmune hepatitis (AIH) is a chronic and generally progressive disease without exactly-identified etiology. Objectives: This study aimed to determine the prevalence of OCI among patients with AIH and to evaluate the tests used to rule out HCV infection in diagnosing AIH. Patients and Methods: Between July 2012 to February 2013, 35 Iranian patients with AIH who attended Tehran Hepatitis Center were investigated. For identifying OCI, detection of HCV RNA in both ultracentrifuged serum samples and peripheral blood mononuclear cells (PBMCs) was used. Data analysis was performed using SPSS. Results: Six males and 29 females with mean disease duration of 77.1 ± 39.5 month and mean age of 43.62 ± 12.67 years were investigated. All cases were negative for anti-HCV antibody and we could not find any HCV RNA in ultracentrifuged serum samples and PBMCs. Conclusions: With our laboratory diagnostic method, it seems that there are no cases of OCI in patients with AIH. However, we recommend further studies with more samples and more precise laboratory method. PMID:25337141

Rezaee Zavareh, Mohammad Saeid; Alavian, Seyed Moayed; Karimisari, Hamidreza; Shafiei, Mostafa; Saiedi Hosseini, Seyed Yasser

2014-01-01

388

Hepatic encephalopathy: An approach to its multiple pathophysiological features  

PubMed Central

Hepatic encephalopathy (HE) is a neuropsychiatric complex syndrome, ranging from subtle behavioral abnormalities to deep coma and death. Hepatic encephalopathy emerges as the major complication of acute or chronic liver failure. Multiplicity of factors are involved in its pathophysiology, such as central and neuromuscular neurotransmission disorder, alterations in sleep patterns and cognition, changes in energy metabolism leading to cell injury, an oxidative/nitrosative state and a neuroinflammatory condition. Moreover, in acute HE, a condition of imminent threat of death is present due to a deleterious astrocyte swelling. In chronic HE, changes in calcium signaling, mitochondrial membrane potential and long term potential expression, N-methyl-D-aspartate-cGMP and peripheral benzodiazepine receptors alterations, and changes in the mRNA and protein expression and redistribution in the cerebral blood flow can be observed. The main molecule indicated as responsible for all these changes in HE is ammonia. There is no doubt that ammonia, a neurotoxic molecule, triggers or at least facilitates most of these changes. Ammonia plasma levels are increased two- to three-fold in patients with mild to moderate cirrhotic HE and up to ten-fold in patients with acute liver failure. Hepatic and inter-organ trafficking of ammonia and its metabolite, glutamine (GLN), lead to hyperammonemic conditions. Removal of hepatic ammonia is a differentiated work that includes the hepatocyte, through the urea cycle, converting ammonia into GLN via glutamine synthetase. Under pathological conditions, such as liver damage or liver blood by-pass, the ammonia plasma level starts to rise and the risk of HE developing is high. Knowledge of the pathophysiology of HE is rapidly expanding and identification of focally localized triggers has led the development of new possibilities for HE to be considered. This editorial will focus on issues where, to the best of our knowledge, more research is needed in order to clarify, at least partially, controversial topics. PMID:22489256

Perazzo, Juan Carlos; Tallis, Silvina; Delfante, Amalia; Souto, Pablo Andrés; Lemberg, Abraham; Eizayaga, Francisco Xavier; Romay, Salvador

2012-01-01

389

[Speech impairment predisposes to cognitive deterioration in hepatic encephalopathy].  

PubMed

Hepatic encephalopathy is a reversible neuro-psychiatric syndrome that complicates liver insufficiency. The changes are complex and disorders are detected in digestive and neural systems. Disturbed consciousness and intellectual deterioration, particularly communicative difficulties are observed: speech is slurred, voice monotonous, writing disturbances, amimic face and rigid posture. Difficulties of socialization and tendency to self-isolation are observed. Memory, attention and perception are decreased. We suppose that disorders of cognitive functions are determined by impairment of speech and other communicative abilities. According to the theories of linguistic determinism and linguistic relativity thought categories move through the mould of native language. That means, speech impairment causes misperception of the real world. To confirm this hypothesis we investigated 106 patients with following diseases: peptic ulcer - 46, fatty liver - 30, liver cirrhosis - 19, viral hepatitis - 11 and 19 controls. Brain magnetic resonance tomography was carried out and psychometric tests were performed to patients with symptoms of hepatic encephalopathy. Atrophic changes in frontal, temporal and insular area of brain cortex were revealed in most cases. Those regions are responsible for actor observation, imitation and emotion, i.e. for empathy and sociability. They are very sensitive to the increased levels of ammonia and glutamine. In case of early treatment only slight atrophic changes are presented but without treatment atrophic processes become stable and expressed by impairments of speech and entire communicative ability. Human beings are very much at the mercy of the particular language which has become the medium of expression for their society. They do not live in the objective world alone, or in the world of social activity alone. Accordingly, damage of speech in hepatic encephalopathy is primary and predisposes to cognitive dysfunction. PMID:20495225

Meparidze, M M; Kodua, T E; Lashkhi, K S

2010-04-01

390

Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by diallyl trisulfide.  

PubMed

The present investigation was aimed to investigate the possible protective role of diallyl trisulfide (DATS) against arsenic (As)-induced hepatic mitochondrial toxicity in rats. Mitochondria were isolated from the liver tissue of rats from all the groups. Lipid profile, lipid peroxidation, antioxidant enzyme activities, hepatic function enzymes, mitochondrial swelling, cytochrome c oxidase activity, mitochondrial Ca(+)-ATPase and Na(+)/K(+)-ATPase activity, mitochondrial calcium content and mitochondrial enzyme activities were measured. Short-term As exposure (5?mg/kg?bw/d for 28?d) caused liver damage as evidenced by changes in activities of liver enzymes. The effects of As were coupled with enhanced reactive oxygen species generation, mitochondrial swelling, inhibition of cytochrome c oxidase, complex I-mediated electron transfer, decreased Ca(2+)-ATPase and Na(+)/K(+)-ATPase activity, a reduction in mitochondrial calcium content, changes in indices of hepatic mitochondrial oxidative stress, significant increase in mitochondrial lipid peroxidation products and alterations in mitochondrial lipid profile. Significant decreases in mitochondrial antioxidants and tricarboxylic acid cycle enzymes were also found in the liver mitochondria of As-induced hepatic mitochondrial toxicity in rats. As also increased hepatic caspase-3 activity and DNA fragmentation. All these apoptosis-related molecular changes caused by As could be alleviated by supplementation with DATS, which likely suggests a protective role against As-induced hepatotoxic changes and hepatic mitochondrial toxicity. The protective effect of DATS on the liver mitochondria was evidenced by altering all the changes induced by As. Free radical scavenging and metal chelating activities of DATS may be the mechanism, responsible for the protective action against As-induced mitochondrial damage in liver. PMID:24295472

Miltonprabu, S; Sumedha, N C

2014-02-01

391

A Plant Kavalactone Desmethoxyyangonin Prevents Inflammation and Fulminant Hepatitis in Mice  

PubMed Central

Alpinia pricei Hayata is a Formosan plant which has been popularly used as nutraceutical or folk medicine for inflammation and various disorders. An active compound of the plant rhizomes, desmethoxyyangonin (DMY), was identified in this study for its novel effect against endotoxin lipopolysaccharide (LPS)-stimulated inflammation in murine macrophages and LPS/D-galactosamine (LPS/D-GalN)-induced fulminant hepatitis in mice. DMY was observed to significantly inhibit proliferation and activation of T cells ex vivo and the activity of several pro-inflammatory mediators in vitro. DMY also protected LPS/D-GalN?induced acute hepatic damages in mice through inhibiting aminotransferases activities and infiltrations of inflammatory macrophages, neutrophils and pathogenic T cells into the liver tissues. In addition, pretreatment with DMY significantly improved the survival rate of LPS/D-GalN?treated mice to 90% (9/10), compared to LPS/D-GalN?treated group (40%, 4/10). UPLC/MS platform-based comparative metabolomics approach was used to explore the serum metabolic profile in fulminant hepatic failure (FHF) mice with or without the DMY pretreatment. The results showed that LPS/D-GalN?induced hepatic damage is likely through perturbing amino acid metabolism, which leads to decreased pyruvate formation via catalysis of aminotransferases, and DMY treatment can prevent to a certain degree of these alterations in metabolic network in mouse caused by LPS/D-GalN. Mechanistic investigation demonstrated that DMY protects LPS or LPS/D-GalN?induced damages in cell or liver tissues mainly through de-regulating IKK/NF?B and Jak2/STAT3 signaling pathways. This report provides evidence-based knowledge to support the rationale for the use of A. pricei root extract in anti-inflammation and also its new function as hepatoprotetive agent against fulminant hepatitis. PMID:24143247

Huang, Chi-Chang; Cheng, Ya-Wen; Chien, Shih-Chang; Wang, Sheng-Yang; Shyur, Lie-Fen

2013-01-01

392

Laser Damage Lab  

NASA Technical Reports Server (NTRS)

Optical Damage Threshold Testing Instrumentation at NASA Langley Research Center. This work was sanctioned and funded by Code Q, R, & AE to develop a new standard for damage testing various types of optical materials and coatings. Laser Induced Damage Threshold (LIDT) testing is a destructive test procedure to determine the minimum applied laser energy level that will result in damage and is referred to as the damage threshold. The damage threshold is often the critical limitation in the section of optical materials for use in high-energy laser systems.The test station consists of diagnostic equipment, beam conditioning optical elements, an inspection microscope and three lasers: a high energy pulsed ND: Yag, which develops 650mJ at 10 hz and outputs three wavelengths which include 1.06m, 532nm and 355 nm; a Ti:sapphire laser which produces a continuum of laser output from 790nm to 900nm; and a alignment HeNe, which looks yellow when mixed with the 2nd harmonic ND:Yag laser. Laser sources are used to perform damage threshold testing at the specific wavelength of interest.

1993-01-01

393

War Damage Assessment  

NASA Technical Reports Server (NTRS)

During and after the Persian Gulf war, hundreds of "oil lakes" were created in Kuwait by oil released from damaged wells. The lakes are a hazard to the Kuwait atmosphere, soil and ground water and must be carefully monitored. Boston University Center for Remote Sensing, assisted by other organizations, has accurately mapped the lakes using Landsat and Spot imagery. The war damage included the formation of over 300 oil lakes, oil pollution and sand dune movement. Total damage area is over 5,400 square kilometers - 30 percent of Kuwait's total surface area.

1994-01-01

394

Assessing tubal damage  

PubMed Central

The fallopian tube plays an important role in the mechanical transport and physiological sustenance of the gametes and early conceptus. Complex and coordinated neuromuscular activity, cilial action and endocrine secretions are required for successful tubal function. Compromised tubal damage can occur after external or internal injury, inhibiting the normal transport of gametes. The overall prognosis for fertility depends principally on the insult and the severity of the tissue damage; hence, assessment of tubal damage plays a major role in predicting occurrence of pregnancy and the likelihood of developing ectopic pregnancy. PMID:19562067

Patil, Madhuri

2009-01-01

395

Hepatitis B Genotypes in Iran  

PubMed Central

Hepatitis B virus (HBV) infection is a public health problem as a cause of liver diseases including hepatocellular carcinoma and cirrhosis. It is estimated that 350 million people live with chronic infection and about one million people die every year from complication of this chronic disease in the world. So far, ten HBV genotypes (A-J) has been identified which show a geographical distribution. Throughout the world, carrier variability rate for hepatitis B infection is estimated to be 0.1% to 20%, with regions classified as having low endemicity (<2%), intermediate endemicity (2-7%) and high endemicity (>8%). The prevalence of hepatitis B infection is estimated at 2 to 7 percent In Iran. After HBV vaccination program the prevalence of hepatitis B infection has been reported less than 2%, so Iran can be considered one of the countries with low HBV infection endemicity. In Iran several studies were shown that the only genotype of HBV(100%)was found genotype D as the prominent type in some provinces, but some studies reported genotype B(5%)as well as genotype D(95%).The distribution of HBV genotypes may guide us in determining disease burden, prognosis and antiviral responses. So, it is important to know the epidemiologically of HBV genotyping as well. PMID:24944540

Haghshenas, Mohammad Reza; Arabi, Mohsen; Mousavi, Tahoora

2014-01-01

396

Optimal management of alcoholic hepatitis.  

PubMed

Alcoholic hepatitis, a clinical syndrome among people with chronic and active alcohol abuse presents with with jaundice and liver failure with or without hepatic encephalopathy. In patients with severe episode, this condition has a potential for 40-50% mortality within a month of presentation. Corticosteroids and pentoxifylline, only available current treatment options provide only about 50% survival benefit. Response to corticosteroids can only be assessed at 1 week of initiation of these drugs using Lille score or documentation of improvement in bilirubin levels. Requirement of minimum 6 months abstinence for liver transplantation cannot be met for alcoholic hepatitis patients who fail to respond to steroids. Emerging data on the benefit of liver transplantation for select patients with first episode of severe AH with non-response to steroids are encouraging. There remains an unmet need for studies assessing newer therapeutic targets and drugs and for optimizing the currently available treatment options. In this regard, decision to promote clinical and translational research by the National Institute of Alcohol Abuse and Alcoholism will be helpful in improving survival of patients with alcoholic hepatitis. PMID:24632766

Raff, E; Singal, A K

2014-03-01

397

Natural history of hepatitis C.  

PubMed

There has long been evidence that hepatitis C can lead to persistent infection in a high proportion of infected individuals, and can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). The transition from acute to chronic hepatitis C is usually sub-clinical. Accurate studies of the time course for clearance of acute hepatitis C are difficult to carry out because of the silent onset of the acute disease. The likelihood of spontaneous HCV resolution is associated with several genetic factors, including IL28B inheritance and the DQB1*0301 allele of the major histocompatibility complex class II. Most data suggest that resolution in the acute phase without progression to chronic disease is not accompanied by significant disease, but minor histological lesions have been observed in anti-HCV positive, HCV RNA negative individuals. The risk of reinfection remains a possibility after clearance of acute hepatitis C. High rates of sexually-transmitted infection are being reported in HIV positive men who have sex with men (MSM). Chronic infection with HCV is the leading cause of end-stage liver disease, hepatocellular carcinoma (HCC) and liver related death in the Western world. The natural history of the chronic disease remains incompletely defined. It is generally a slowly progressive disease characterized by persistent hepatic inflammation, leading to the development of cirrhosis in approximately 10-20% of patients over 20-30 years of HCV infection. However, the published data indicate varying progression rates to cirrhosis. Overall, once cirrhosis has developed there is a 1-5% annual risk of HCC and a 3-6% annual risk of hepatic decompensation. Following an episode of decompensation the risk of death in the following year is between 15% and 20%. The high number of chronically infected individuals, the burden of disease, and the absence of a vaccine indicates that treatment will form part of the disease control but the impact, effectiveness and outcomes of treatment in various groups remain uncertain. Several studies and meta-analysis have concluded that eradication of HCV with antiviral therapy reduces the risk of HCC in patients with chronic hepatitis C, independent of fibrosis stage, but the risk is not eliminated. PMID:25443346

Westbrook, Rachel H; Dusheiko, Geoffrey

2014-11-01

398

Eltrombopag in chronic hepatitis C  

PubMed Central

Chronic hepatitis C is a public health problem worldwide. Unfortunately, not all patients may benefit from antiviral therapy due to thrombocytopenia. Its causes are represented by portal hypertension and platelet sequestration in the spleen, decreased serum levels or activity of thrombopoietin, the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon. Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients. Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner. Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia. Its indication for other hemopathies or situations (like thrombocytopenia secondary to chemo- or radiotherapy, acute leukemia, myelodysplastic syndroms, acquired and hereditary bone marrow failure, and platelet donors) is under study. Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment. We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus, highlighting the benefits and mentioning possible adverse effects. In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery. Eltrombopag is a solution for many of these patients, which allows them receiving antiviral therapy and sometimes getting a sustained virological response, but they must be well monitored to prevent possible thromboembolic or bone marrow complications or liver failure occurrence. PMID:25253952

Mih?il?, Romeo-Gabriel; Cip?ian, Remus-C?lin

2014-01-01

399

Hepatitis A: Old and New  

PubMed Central

The hepatitis A virus (HAV), a picornavirus, is a common cause of hepatitis worldwide. Spread of infection is generally person to person or by oral intake after fecal contamination of skin or mucous membranes; less commonly, there is fecal contamination of food or water. Hepatitis A is endemic in developing countries, and most residents are exposed in childhood. In contrast, the adult population in developed countries demonstrates falling rates of exposure with improvements in hygiene and sanitation. The export of food that cannot be sterilized, from countries of high endemicity to areas with low rates of infection, is a potentially important source of infection. After ingestion and uptake from the gastrointestinal tract, the virus replicates in the liver and is excreted into the bile. Cellular immune responses to the virus lead to destruction of infected hepatocytes with consequent development of symptoms and signs of disease. Humoral immune responses are the basis for diagnostic serologic assays. Acute HAV infection is clinically indistinguishable from other causes of acute viral hepatitis. In young children the disease is often asymptomatic, whereas in older children and adults there may be a range of clinical manifestations from mild, anicteric infection to fulminant hepatic failure. Clinical variants include prolonged, relapsing, and cholestatic forms. Management of the acute illness is supportive, and complete recovery without sequelae is the usual outcome. Research efforts during World War II led to the development of passive immunoprophylaxis. Pooled immune serum globulin is efficacious in the prevention and attenuation of disease in exposed individuals. More recently, active immunoprophylaxis by vaccination has been accomplished. Future eradication of this disease can now be contemplated. PMID:11148002

Cuthbert, Jennifer A.

2001-01-01

400

Controlling Mole Damage  

E-print Network

Moles can cause much damage to crops and livestock. This leaflet explains the proper way to set shocker loop traps and harpoon traps. Cultural controls and habitat modifications are discussed. Moles also can be controlled with toxicants...

Texas Wildlife Services

2007-03-13