Influence of chronic ethanol consumption on hamster liver microsomal O-dealkylase activities and cytochrome b5 content.
The effects of two different methods of administering ethanol to hamsters on liver microsomal cytochrome levels and the activities of ethoxyresorufin O-deethylase and p-nitroanisole O-demethylase have been examined. Administration of ethanol in liquid diets resulted in enhanced levels of cytochrome P-450, NADPH-supported aniline hydroxylase (Form I), and both NADPH- and NADH-supported p-nitroanisole O-demethylase. NADH-ferricyanide reductase was also increased. No change in NADPH-cytochrome c reductase or in the NADPH-supported rate of ethoxyresorufin O-deethylase was observed. In contrast, both NADH-supported ethoxyresorufin O-deethylase and cytochrome b5 levels were decreased. Administration of ethanol in the drinking water to chow-fed animals had no effect on total cytochrome P-450 levels; however, the rates of NADPH-supported aniline hydroxylase (Form I) and p-nitroanisole O-demethylase activity were increased. No changes in NADPH-cytochrome c reductase, NADH-ferricyanide reductase, or NADH-supported p-nitroanisole O-demethylase activity were noted. Cytochrome b5 levels were decreased as were both the NADPH- and NADH-supported rates of ethoxyresorufin O-deethylase. These data suggest that chronic consumption of ethanol by hamsters either in liquid diet form or as ethanol-water solutions to chow-fed animals lowers cytochrome b5 levels. When cytochrome b5 levels are lowered and total chromosome P-450 levels remain unchanged, the NADPH-supported rate of microsomal O-dealkylation of ethoxyresorufin is decreased. These data suggest that cytochrome b5 participates in the NADPH-supported microsomal O-dealkylation of ethoxyresorufin.
D000818:Animals; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003573:Cytochrome b Group / Q000032:analysis*; D015786:Cytochromes b5; D004041:Dietary Fats / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D010088:Oxidoreductases / Q000032:analysis*; D010090:Oxidoreductases, O-Demethylating / Q000032:analysis*
D003573:Cytochrome b Group; D004041:Dietary Fats; D009243:NAD; D000431:Ethanol; D009249:NADP; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; C026048:4-nitroanisole O-demethylase; D010088:Oxidoreductases; D010090:Oxidoreductases, O-Demethylating; D019363:Cytochrome P-450 CYP1A1