Effects of acute ethanol administration and chronic ethanol feeding on mixed function oxidation in deermice lacking ADH.
Hepatic microsomes catalyze the oxidation of ethanol and other drugs. The mechanisms through which ethanol alters mixed function oxidation are still debated. There is evidence that ethanol and drugs interact at a microsomal level, but there are also claims that ethanol may interfere with drug metabolism indirectly by affecting the supply of NADPH through NADH production in the ADH pathway. To investigate the role of chronic ethanol consumption, deermice with normal liver ADH (ADH+) or genetically lacking ADH (ADH-) were pair-fed liquid diets containing ethanol or isocaloric carbohydrate for 23 days. The acute effects of ethanol were studied in deermice fed standard laboratory chow and tap water ad lib. In vivo and in vitro, the effects of an acute dose of ethanol and chronic ethanol feeding on mixed function oxidation as measured by the demethylation of aminopyrine were similar in both animal strains. Statistical analysis showed no significant differences between ADH+ and ADH- animals under all experimental conditions studied. We conclude that induction and inhibition of mixed function oxidation by ethanol may be related to the interaction of ethanol with hepatic microsomes rather than to redox changes produced by ADH mediated ethanol metabolism.
Gellert
J
J
Lieber
C S
CS
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000172:deficiency* / Q000502:physiology; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D003640:Dealkylation; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000032:analysis*; D010084:Oxidation-Reduction; D010542:Peromyscus
D000632:Aminopyrine; D000431:Ethanol; D006899:Mixed Function Oxygenases; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase