The Effects of Chronic Ethanol Ingestion on Ethanol Binding to Hepatic Cytochrome P‐450 and on Certain Hepatic and Renal Parameters in the “Long Sleep” and “Short Sleep” Mouse

Abstract

Male mice selected for genetic differences in ethanol-induced sleep time, thereby designated long sleep (LS) and short sleep (SS), were treated with the Lieber-DeCarli liquid diet for 25 days. This chronic ethanol treatment produced an increase in liver/body weight and kidney/body weight in SS mice only. In addition, chronic ethanol treatment produced significant increases in both LS and SS treated mice in in vivo ethanol elimination, hepatic cytochromes P-450 and B_s, NADPH cytochrome c reductase and hepatic and renal 7-ethoxycoumarin O-de-ethylase activity. Geno-typic differences were observed in the magnitude of response of microsomal ethanol oxidation per mg of microsomal protein (SS > LS). Further, control LS and SS mice possessed substantially different activity of renal 7-ethoxycoumarin O-de-ethylase. Both lines exhibited similar induced renal 7-ethoxycoumarin O-de-ethylase activity after chronic ethanol ingestion. Ethanol binding spectra produced when ethanol was added to hepatic microsomes were examined using double reciprocal plots. Chronic ethanol ingestion produced genotypically related (LS > SS) increases in the absorbance change maximum per mg of microsomal protein. No significant changes in the spectral dissociation constant or absorbance change maximum per nM cytochrome P-450 were observed following ethanol treatment.