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)

The effect of tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1) alpha, which are thought to be principal mediators inducing homeostatic abnormalities during endotoxemia, were investigated on cultured hepatocytes in an attempt to understand their role in the pathogenesis of fulminant hepatitis. Both TNF and IL-1 had no direct cytotoxicity on cultured adult rat hepatocytes as assessed by their effects on protein synthesis and also cytosolic enzyme activity released into the culture medium in the presence of 5 mM D-galactosamine (Ga1N). However, IL-1 caused a dose-dependent inhibition of DNA synthesis in cultured adult rat hepatocytes. Moreover, the serum from TNF-treated rats, prepared after intravenous administration of TNF (5 X 10(4) U per rat), caused a significant increase of enzyme release into culture medium in contrast to control rat serum. The cytotoxicity disappeared when the serum from TNF-treated rats was pretreated by heating at 56 degrees C for 30 min, and was decreased by the addition of the protease inhibitor, aprotinin. In vivo, gabexate mesilate, a serine-type protease inhibitor, prevented GalN/TNF-induced fulminant hepatitis, whereas MX-1, an anti-complement agent, had no such effect. These results strongly suggest that IL-1 has a inhibitory effect on hepatocytes in terms of DNA synthesis and that TNF indirectly induces hepatocellular damage through the serine proteases which are possibly activated by the cytokine in vivo.
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PMID:Significance of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in the pathogenesis of fulminant hepatitis: possible involvement of serine protease in TNF-mediated liver injury. 191 53

The Long-Evans rat with a cinnamon-like coat color (LEC rat) is a mutant strain displaying hereditary hepatitis with severe jaundice. The age related difference in microsomal dealkylation of pentoxyresorufin and ethoxyresorufin was examined. The enzyme activity levels of pentoxyresorufin O-depentylase in LEC rats were decreased to 25% of the levels in control [Long-Evans rats with an agouti coat color (LEA rats)]. In contrast, ethoxyresorufin O-deethylase exhibited a much less marked difference between the strains. In parallel with these strain differences in enzyme activities, a decrease in phenobarbital (PB) inducible P450 isozymes, mainly P450b and P450e, was observed by Western blot analysis. The level of P450PB in LEC rats was more markedly depressed than in the LEA strain. On the other hand, microsomes from uninduced LEC rat liver had more 3-methylcholanthrene (MC) inducible P450MC, mainly P450c and P450d, than microsomes from LEA rat liver and these isozymes in the LEC were markedly induced by 3-methylcholanthrene treatment. The great difference in cytochrome P450PB content of the liver microsomes between LEC and LEA rats and the maintained constitutive levels of hepatic cytochrome P450MC in the LEC rats suggest a possible role of these cytochrome isozymes in the onset of spontaneous hepatitis and hepatoma.
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PMID:Selective expression and induction of cytochrome P450PB and P450MC during the development of hereditary hepatitis and hepatoma of LEC rats. 280 35

The evolution of today's accepted theories regarding the pathogenesis of halothane-induced hepatitis (HIH) is traced from a selection of the extensive literature covering this rare condition. Initial postulates indicted an immunological mechanism. The development of a laboratory model (starved, phenobarbitone-pretreated, hypoxic rat) uncovered two other 'triggers': highly reactive (toxic) free-radical intermediates generated from a reductive metabolic pathway; and hypoxic stress alone. None of these proposed mechanisms incontrovertibly excludes the other and complex interrelationships may exist. Continuing research utilizing sophisticated analytical tools and new HIH animal models suggests that the field remains incompletely explored.
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PMID:Perspectives in the pathogenesis of halothane-induced hepatitis. 352 Aug 83

Thymalfasin (thymosin-alpha 1) is an immunomodulating agent able to enhance the Th1 immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases, including chronic hepatitis B and C, AIDS, primary immunodeficiency diseases, depressed response to vaccination and cancer. The basis for effectiveness in these conditions is primarily through modulation of immunological responsiveness, as thymalfasin has been shown to have beneficial effects on numerous immune system parameters and to increase T-cell differentiation and maturation. Thymalfasin is responsible for reconstitution of immune function when thymic tissue is given back to thymectomized animals. In addition, thymalfasin has been shown to have efficacy in multiple experimental models of immune dysfunction, mainly, infectious diseases such as hepatitis (woodchuck) and influenza (mouse), and cancer such as melanoma (mouse) and colorectal carcinoma (rat) where thymalfasin has shown antitumor effects.
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PMID:Thymalfasin: an immune system enhancer for the treatment of liver disease. 1554 53

Thymalfasin (thymosin-alpha 1) is an immunomodulating agent able to enhance the Thl immune response. It has been evaluated for its immunomodulatory activities and related therapeutic potential in several diseases, including chronic hepatitis B and C, AIDS, primary immunodeficiency diseases, depressed response to vaccination and cancer. The basis for effectiveness in these conditions is primarily through modulation of immunological responsiveness, as thymalfasin has been shown to have beneficial effects on numerous immune system parameters and to increase T-cell differentiation and maturation. Thymalfasin is responsible for reconstitution of immune function when thymic tissue is given back to thymectomized animals. In addition, thymalfasin has been shown to have efficacy in multiple experimental models of immune dysfunction, mainly, infectious diseases such as hepatitis (woodchuck) and influenza (mouse), and cancer such as melanoma (mouse) and colorectal carcinoma (rat) where thymalfasin has shown antitumor effects.
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PMID:Thymalfasin: an immune system enhancer for the treatment of liver disease. 1564 Dec 7

Molecular regulation of fibrosis in chronic canine hepatitis is poorly understood. The authors employed quantitative polymerase chain reaction (PCR) to determine the expression levels of genes reported to be related to fibrosis in other species (human, mouse, and rat) and to elucidate the relationship of these genes with the degree of fibrosis and the presence or absence of ascites and/or jaundice in dogs with hepatitis. Nine fibrosis-related genes were assayed: PDGFB, PDGFD, MMP2, TIMP1, THBS1, COL1A1, COL3A1, TGFB1, and TGFB2. Liver samples of 15 dogs with chronic hepatitis and 4 healthy control dogs were obtained via laparoscopic biopsy and subjected to histologic and quantitative PCR analyses. The expression of all 9 genes showed significant positive correlation (P<.01, r>.70) with the degree of fibrosis. Furthermore, the expression levels of all genes except TGFB1 were significantly higher (P<.05) in dogs with hepatic failure-related symptoms (ascites/jaundice). Results suggest that these 9 genes are integral to the development of fibrosis in canine chronic hepatitis.
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PMID:Expression of fibrosis-related genes in canine chronic hepatitis. 2111