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)

Synergy between exposure to chemical carcinogens (nitrosamines) and infestation with the liver fluke Opisthorchis viverrini has been demonstrated in a hamster model of hepatocarcinogenesis (Flavell et al., Carcinogenesis 4:927-930, 1983; Thamavit et al., Carcinogenesis 8:1351-1353, 1987). To elucidate the mechanisms of this interaction we tested the hypothesis that liver parasitism might influence the expression and activity of carcinogen metabolizing enzymes. We found that one, and perhaps more, hamster liver cytochrome P450 (CYP) isozymes immunorelated to mouse CYP2A5 contributed up to 50 or 60% of the hepatic aflatoxin B1 (AFB) and N-nitrosodiethylamine (NDEA) metabolism, respectively. As inferred from average enzyme activities and from western blot, immunoinhibition, and substrate (coumarin) inhibition analyses, O. viverrini infestation increased the expression of enzymes detectable by anti-CYP2A5 antibody as well as NDEA metabolism in male but not in female hamsters. Immunohistochemical analysis of CYP2A expression by anti-mouse CYP2A5 antibody demonstrated that the O. viverrini-associated increase was not uniformly distributed throughout the liver but occurred in hepatocytes immediately adjacent to areas of inflammation. Immunohistochemical analysis of AFB-DNA adducts in the livers of O. viverrini-infested hamsters treated with AFB showed that the highest levels of adducts were found in the regions of liver where hepatocellular expression of enzymes detectable by anti-CYP2A5 antibody is induced. These results suggest that a high local expression of CYP isozymes in O. viverrini-infested livers could be a contributing risk factor in the development of liver cancers associated with parasitic hepatitis.
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PMID:Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver. 791 96

Cirrhosis is the end stage of many forms of liver pathologies including hepatitis. The liver is known for its vital role in the processing of xenobiotics, including drugs and toxic compounds. Cirrhosis causes changes in the architecture of the liver leading to changes in blood flow, protein binding, and drug metabolizing enzymes. Drug metabolizing enzymes are primarily decreased due to loss of liver tissue. However, not all enzyme activities are reduced and some are only altered in specific cases. There is a great deal of discrepancy between various reports on cytochrome p450 alterations in liver cirrhosis, likely due to differences in disease severity and other underlying conditions. In general, however, CYP1A and CYP3A levels and related enzyme activities are usually reduced and CYP2C, CYP2A, and CYP2B are mostly unaltered. Both alcohol dehyrogenases and aldehyde dehydrogenases are altered in liver cirrhosis, although the etiology of the disease may determine the expression of alcohol dehydrogenases. Glucuronidation is mainly preserved, but there are a number of factors that determine whether glucuronidation is affected in patients with liver cirrhosis. Low sulphation rates are usually found in patients with liver disease but a decrease in sulfatase activity compensates for the decrease in sulphation rates. In all cases, a reduction in drug metabolizing enzyme activities in liver cirrhosis contributes to decreased clearance of drugs seen in patients with liver abnormalities. The reduction in drug metabolizing enzyme activity must be taken into consideration when adjusting doses, especially in patients with severe liver disease.
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PMID:The effect of liver cirrhosis on the regulation and expression of drug metabolizing enzymes. 1507 93