Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simultaneous intraperitoneal administration of 700 mg/kg galactosamine and 33 micrograms/kg Salmonella abortus equi endotoxin to male NMRI albino mice resulted in fulminant hepatitis as assessed after nine hours by measurement of serum transaminases as well as sorbitol dehydrogenase activities. Intraperitoneal pretreatment of animals with 2 X 100 mg/kg allopurinol, or intravenous pretreatment with 33 kU superoxide dismutase or 1 MU catalase fully prevented hepatitis. Administration of 10 micrograms/kg of the prostacyclin analogue iloprost antagonized liver injury when given simultaneously with galactosamine/endotoxin but did not protect when given 90 min later. Tocopherol or desferal pretreatment of the animals had no significant protective effect. Together with our recent finding that hepatic leukotriene D4 production is likely to be responsible for galactosamine/endotoxin-induced hepatitis we interpret these results as evidence for a leukotriene-induced hepatic ischemia followed by a reperfusion syndrome.
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PMID:Evidence for the involvement of a reperfusion injury in galactosamine/endotoxin-induced hepatitis in mice. 360 63

As free radicals and lipid peroxidation are involved in the pathogenesis of different inflammatory diseases of the liver, the blood malondialdehyde content, the activity or quantity of free radical eliminating enzymes and the natural antioxidant, vitamin E serum level has been studied in ten patients with chronic active hepatitis and in six subjects with alcoholic liver disease. Thirty healthy volunteers served as controls. The serum malondialdehyde/thiobarbituric acid reactive substance and its concentrations increased significantly in both hepatitis groups. The superoxide dismutase content was also raised in the patients' sera. The serum glutathione peroxidase (GSH-Px) activity was decreased in both groups, while the red blood cell GSH-Px showed a significantly lower activity in the alcoholic hepatitis patients. Serum catalase activity and vitamin E levels in both types of chronic hepatitis were not significantly different from the healthy controls.
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PMID:Studies of the blood lipid peroxide status and vitamin E levels in patients with chronic active hepatitis and alcoholic liver disease. 375 86

We have previously shown that supplemental vitamin E has a cytoprotective effect in the liver of rats with chronic CCL4-induced liver cirrhosis. In this study, we hypothesized that vitamin E would have a protective effect in acute liver injury induced by D-galactosamine. D-Galactosamine-induced injury has been thought to be due to a synergistic direct toxic effect and presence of intestinal bacteria and/or endotoxins. D-Galactosamine was used to induce acute "hepatitis" (1.5-2.0 g/Kg body weight, ip). Rats were placed on either standard chow or the same chow supplemented with vitamin E (300 mg DL-alpha-tocopherol/Kg diet) and 6 days later were given D-galactosamine. There was significantly improved early (5-day) survival and late (14-day) survival in the vitamin E-supplemented group. The vitamin E beneficial effect was manifested also by decreased liver fat and collagen content and decreased SGPT level. Because bacterial endotoxins have been implicated as playing a role in the pathogenesis of D-galactosamine hepatitis, the same experiment was carried out using germ-free and conventional rats. There was significantly improved survival in both the germ-free and conventional vitamin E-supplemented groups both at 5 and 14 days. There was no significant difference between conventional and germ-free rats with or without vitamin E supplementation. In summary (a) vitamin E improves the early fat and collagen accumulation in the liver, decreases SGPT level, and improves survival in the D-galactosamine experimental model of acute liver injury in both conventional and germ-free rats; and (b) D-galactosamine toxicity is probably not mediated through intestinal bacteria and/or endotoxins.
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PMID:Protective effect of vitamin E in rats with acute liver injury. 395 25

Serum levels of alpha-tocopherol (vitamin E) were determined in various types of liver diseases, and as a results, it was revealed that serum alpha-tocopherol was significantly depressed in acute hepatitis (p less than 0.01, n = 22), alcoholic hepatitis (p less than 0.001, n = 9) and fulminant hepatitis (p less than 0.001, n = 6). There was a significant correlation between serum levels of alpha-tocopherol and beta-lipoprotein (r = 0.92, p less than 0.001, n = 17). Though there was no correlation between serum levels of alpha-tocopherol and triglyceride, there was a significant correlation between alpha-tocopherol and cholesterol (r = 0.57, p less than 0.01, n = 21), and phospholipid (r = 0.49, p less than 0.05, n = 18). There was no correlation between serum levels of alpha-tocopherol and other liver function tests. These facts suggested that the diminished serum vitamin E in patients with liver diseases is ascribable to the depression in blood level of beta-lipoprotein that results from liver disorders, because the liver is the major supply source of beta-lipoprotein.
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PMID:alpha-Tocopherol level in liver diseases. 715 92

Following the pioneer report of Di Luzio (Physiologist 6, 169-173, 1963) concerning the prevention of the acute ethanol-induced fatty liver by antioxidants, many observations have shown that ethanol-induced liver injury may be linked, at least partly, to an oxidative stress resulting from increased free radical production and/or decreased antioxidant defence. The disturbances induced in the major hepatic enzymatic and non-enzymatic antioxidant systems following experimental acute and chronic ethanol administration are reviewed, emphasizing the important role of dietary alpha-tocopherol in modifying the induction of oxidative stress and its usual expression as increased lipid peroxidation. Adaptative increases in some elements of the hepatic antioxidant defence partly counteract the enhanced generation of prooxidant free radicals following chronic ethanol intake. By contrast, lipid peroxidation is favoured when ethanol is administered together with a fat-rich diet and/or various xenobiotics. Chronic ethanol feeding has also been reported to potentiate the oxidative stress resulting from an acute ethanol load. By generating potent chemoattractants for human neutrophils and/or by stimulating the expression of genes involved in collagen biosynthesis, liver lipid peroxidation may play an important role in the progression of steatosis to hepatitis and cirrhosis. Oxidative stress has been shown not to be restricted to the liver, but also to affect, under some experimental conditions of ethanol administration, extrahepatic tissues, such as the central nervous system, the heart and the testes. This stress can be partly prevented by vitamin E supplementation. Ethanol-induced antioxidant disturbances have also been reported in clinical studies in blood and liver biopsies. Pharmacological antioxidants could have beneficial effects in reducing the incidence of ethanol-induced changes in cellular lipids, proteins and nucleic acids. The antioxidants considered could act by reducing free radical production (e.g. chelators of redox-active iron derivatives), trapping free radicals themselves, interrupting the peroxidation process or reinforcing the natural antioxidant defence.
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PMID:Alcohol and antioxidant systems. 781 35

An increasing number of studies support the involvement of free radical-mediated oxidative reactions in the pathogenesis of tissue injury following ischemia reperfusion. In particular, a condition of oxidative stress is evident in patients with circulatory shock, a disease process often complicated by progressive organ failure sustained by inflammatory reactions. In all shock patients without signs of organ failure, a consistent increase of intermediate and final products of lipid peroxidation (lipid peroxides and aldehydes respectively) was observed. Impairment of the redox equilibrium in the tissues of these patients was confirmed by a significant reduction of glutathione and vitamin E hematic concentrations. Moreover, a selective increase of plasma aldehyde-protein adducts, actual proof of oxidative damage of macromolecules, is only present in the shock patients who, in addition, show hepatic cytolysis (ischemic hepatitis) as estimated by plasma levels of LDH5 isoenzyme. Aldehyde adducts well mark the progression of the disease towards multiple organ failure. Finally, the good statistical correlation between aldehyde-modified proteins and LDH5, as well as their distinct behaviour in control and ischemic hepatitis, support the involvement of oxidative damage in the expression and worsening of circulatory shock.
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PMID:Oxidative stress in the development of human ischemic hepatitis during circulatory shock. 798 28

Long-Evans Cinnamon (LEC) rats are autosomal recessive mutants that develop hepatitis and hepatocellular carcinoma. Because copper accumulates in the livers of these rats, and some of their clinical and pathological features are similar to those of patients with Wilson's disease, LEC rats are proposed as an animal model of Wilson's disease. It has been thought that unbound copper generates free radicals, which act as hemolytic and hepatocytotoxic agents. To examine the effects of vitamin E as an antioxidant on hereditary hepatitis in LEC rats, we fed 3-week-old rats for 25 weeks either vitamin E-deficient, control, or vitamin E-supplemented diets which contained < 0.01 mg of total tocopherols, 2 mg of d,l-alpha-tocopheryl acetate (2 I.U.), and 58.5 mg of d,l-alpha-tocopheryl nicotinate (50 I.U.), respectively, per 100 mg of feed. In males, body weight loss was first observed in the vitamin E-deficient group, and mean ages at which jaundice occurred were in the order: deficient younger than control younger than supplemented groups. The ages when plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities began to increase sharply and peaked followed the same order. Thus, it is likely that free radicals are involved in jaundice and hepatitis in LEC male rats, and they are a model for studying the relationship of copper, free radicals, and hepatitis. Conversely, in females, no apparent differences in clinical and biochemical changes were observed among the three groups. Causes for the discrepancy between the sexes remain to be clarified.
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PMID:Effects of dietary vitamin E on clinical course and plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities in hereditary hepatitis of LEC rats. 845 79

No published reports compare hepatic alpha-tocopherol (adjusted for hepatic lipid content) with indicators of blood alpha-tocopherol in adult patients with various liver diseases. alpha-Tocopherol was simultaneously measured in liver biopsy tissues and blood from 66 subjects (9 comparison patients hospitalized for biliary tract surgery, 13 with chronic persistent hepatitis, 9 with chronic aggressive hepatitis, 10 with acute hepatitis, 10 with cirrhosis, 7 with both cirrhosis and hepatic cell carcinoma, and 8 with fatty liver). Hepatic, erythrocyte, and plasma alpha-tocopherol concentrations were measured, as were hepatic and serum lipids. The ratios of alpha-tocopherol to total lipid concentrations (Toc/TL ratios) in plasma and liver were calculated. In both comparison patients and patients with chronic persistent hepatitis and fatty liver, hepatic alpha-tocopherol concentrations were strongly correlated with hepatic triglyceride and total lipid concentrations (r = .72, P < .001; and r = .75, P < .001, respectively); the relationships (slopes) when hepatic alpha-tocopherol concentrations were compared with hepatic triglyceride and total lipid concentrations were similar in these patients and in all subjects. No strong correlations were found between hepatic and blood alpha-tocopherol parameters in all subjects. These results suggest that hepatic alpha-tocopherol is present at similar concentrations in triglycerides as well as total cholesterol and phospholipids and that neither plasma Toc/TL ratios nor erythrocyte alpha-tocopherol concentrations are useful indicators of hepatic vitamin E status. The hepatic Toc/TL ratio may be useful to assess total hepatic vitamin E status.
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PMID:Assessment of hepatic vitamin E status in adult patients with liver disease. 925 50

Correcting action of vitamin E and it's short chain derivative on the activity of some mitochondria electron transport chain enzymes were investigated on models of acute and chronic toxic hepatitis. Inhibition of NADH- and succinate-cytochrome c oxidoreductase complexes activity was established in short term action of xenobiotics. Treatment of rats with CCl4 during 60 days lowered activity of NADH-cytochrome c oxidoreductase complex and significantly increased activity of succinate-cytochrome c oxidoreductase complex and succinate dehydrogenase. Obviously, as a result of long term influence of hepatotoxic agents switching over in rat mitochondria electron transport from NAD-dependent way of substrate oxidation to succinate-dependent way took place. This event could be a part of the body adaptation mechanisms. Vitamin E and its short chain analogue corrected activities of investigated enzymes of mitochondria liver in the animals with acute and chronic hepatitis.
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PMID:[Correction of the activity of certain enzymes in the rat liver mitochondrial electron transport chain by derivatives of alpha-tocopheryl acetate in toxic damage to the liver]. 1079 Oct 53

The asialoglycoprotein receptor (ASGP-R) on mammalian hepatocytes provides a unique means for the development of liver-specific carriers, such as liposomes, recombinant lipoproteins, and polymers for drug or gene delivery to the liver, especially to hepatocytes. The abundant receptors on the cells specifically recognize ligands with terminal galactose or N-acetylgalactosamine residues, and endocytose the ligands for an intracellular degradation process. The use of its natural ligand, i.e. asialofetuin, or synthetic ligands with galactosylated or lactosylated residues, such as galactosylated cholesterol, glycolipids, or galactosylated polymers has achieved significant targeting efficacy to the liver. There are several examples of successful targeted therapy for acute liver injury with asialofetuin-labeled and vitamin E-associated liposomes or with a caspase inhibitor loaded in sugar-carrying polymer particles, as well as for the delivery of a new antiviral agent, 9-(2-phosphonylmethoxyethyl)adenine. Liposome-mediated gene delivery to the liver is more difficult than to other organs, such as to lungs. It is still in its infancy due to difficulties in solving general issues, such as the circulatory stability of liposome-DNA complexes, and lysosomal or endosomal degradation of plasmid DNA. In spite of these existing concerns, several new approaches offer some reason for optimism, for example; intravenous injection of asialofetuin- or galactosylated cholesterol-labeled cationic liposomes has led to high transgene expression in the liver. In addition, specific antisense oligonucleotides against woodchuck hepatitis viruses incorporated into sialoorosomucoid-poly-L-lysine significantly inhibited viral replication in the liver. Finally, galactosylated polymers are promising for gene delivery, but require further studies to verify their potential applications.
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PMID:Targeting hepatocytes for drug and gene delivery: emerging novel approaches and applications. 1186 Dec 24


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