Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients.
In liver biopsy material of eighty-nine patients with suspected liver disease the drug-metabolizing function was investigated. The capacity of the liver to oxidatively metabolize drugs was assessed by determination of cytochrome P-450 dependent monooxygenase activity in vitro. The biotransformational function of these microsomal enzymes was tested with compounds representing the activity of oxidative drug metabolism (7-ethoxycoumarin, p-nitroanisol and cytochrome c). From the eight-nine patients sixty-one had various liver diseases not related to ethanol and twenty-eight abused ethanol. When both groups were matched for age, sex, smoking, treatment with sedatives, drugs and degree of liver damage the alcoholic group had significantly higher activities of 7-ethoxycoumarin O-deethylase (EOD: 76.9 +/- 31.1 pmol min-1 mg-1 protein, mean +/- SD) than the non-alcoholic liver disease group (42.7 +/- 14.1). The inducing effect of ethanol was most striking on the EOD activity, less for the O-demethylation of p-nitroanisol (PNA) and not present for the NADPH-cytochrome c reductase. The induced patients were analysed in detail to find out which factors were responsible for the observed scatter of enzyme activities within the alcoholic group. Alcoholics with fatty liver (n = 7) had the highest EOD activities (108.9 +/- 25.0), patients with alcoholic hepatitis (n = 10) had significantly less activity (66.0 +/- 1.9) than the former group. However, alcoholics without liver damage (n = 6) had activities not significantly different (46.0 +/- 15.8) from controls (39.4 +/- 9.1). These subgroups among the alcoholics were comparable in terms of sex, age, smoking and drinking habits.(ABSTRACT TRUNCATED AT 250 WORDS)
D015660:7-Alkoxycoumarin O-Dealkylase; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005235:Fatty Liver, Alcoholic / Q000201:enzymology; D005260:Female; D006519:Hepatitis, Alcoholic / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010105:Oxygenases / Q000096:biosynthesis*
D000431:Ethanol; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase