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

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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 Bs, 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.