Comparative effects of ethanol administration on hepatic monooxygenases in rats and mice

Abstract

The inducing effects of chronic ethanol ingestion on hepatic monooxygenases in Sprague-Dawley and Long-Evans rats, and A/J and C57BL/6J mice, were studied. Cytochrome P-450 content was significantly increased in livers of all animals receiving the experimental ethanol-containing liquid diet. The CO-difference spectra of microsomes from ethanol-treated animals showed a shift in the absorbance maximum to 451–452 nm, compared to the absorbance maximum of 450 nm observed with microsomes from control animals. Ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase activities in livers of ethanol-treated animals were minimally affected. The shift in the absorbance maxima to longer wavelengths in the CO-difference spectrum and the minimal effects on the metabolism of ethylmorphine and benzo[a]pyrene demonstrate that ethanol differs in its inducing properties, when compared to the properties of the two widely used hepatic microsomal enzyme inducers, phenobarbital and 3-methylcholantrhene. In contrast to the minimal effects observed on the metabolism of ethylmorphine and benzo[a]pyrene, several fold increases were observed in hepatic 7-ethoxycoumarin 0-deethylase and aniline hydroxylase activities in the treated animals. Polyacrylamide gel electrophoresis of hepatic microsomes from those animals receiving ethanol revealed protein band(s) in the cytochrome P-450 molecular weight region, the intensities of which were markedly increased relative to that from control animals. The heme-associated peroxidase activity was also increased in the same molecular weight region. The results of the present spectral, catalytic, and electrophoretic studies demonstrate that in mice, as in rats, chronic ethanol treatment causes the induction of specific cytochrome(s) P-450 with preferential activity toward aniline and 7-ethoxycoumarin.