[Enzyme induction of the liver caused by chronic alcoholism as risk factor in hepatotoxicity].
Abuse of ethanol has shown to induce the drug-metabolizing enzyme activity of the liver in rats and in humans. Therefore, we studied cytochrome P-450 dependent monooxygenase and conjugating enzyme activity in needle liver biopsy specimens of patients using the following substrates and enzyme assays: 7-ethoxycoumarin O-deethylase (EOD), p-nitroanisol O-demethylase (PNA), NADPH-cytochrome c reductase, 1-naphtol glucuronyltransferase (NGT). Among alcoholics induction of EOD, PNA and NGT was only found in patients with active alcoholic liver damage (elevated transaminases and necrosis of the liver cells). The other groups had either normal enzyme activity (abstinent alcoholics, residual alcoholic liver damage) or low activity (liver cirrhosis, cholestatic liver disease). Surprisingly, nonabstinent alcoholics with normal liver histology did not reveal enzyme induction. Enzyme induction was dependent on time of abstinence. Within 20 days of abstinence the induction tapered off concomitantly with the resolution of active liver injury. The hyperactive ethanol-induced enzyme system could produce toxic oxygen radicals leading to liver injury and also toxify drugs (paracetamol, halogenated hydrocarbons, INH). Induction of hepatic monooxygenase activity by ethanol, although originally an adaptive response, might therefore increase the risk of hepatotoxicity of certain drugs.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D004790:Enzyme Induction; D006801:Humans; D008099:Liver / Q000201:enzymology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D010105:Oxygenases / Q000096:biosynthesis*; D051381:Rats; D012306:Risk
D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases
Enzyminduktion der Leber durch chronischen Alkoholismus als Risikofaktor der Hepatotoxizität.