Ethanol‐Inducible Cytochrome P‐450: Assessment of Substrates' Specific Chemical Probes in Rat Liver Microsomes

Publisher Website
Google Scholar
Abstract
The capacity of liver microsomes to oxidize various substrates known to be specific of alcohol-inducible cytochrome P-450 was studied in rats treated with different xenobiotics such as 3-methyl-cholanthrene, phenobarbital, acetone, and ethanol. Analysis of results showed a significantly marked increase following ethanol and acetone treatments of the p-nitrophenol hydroxylation (283 .+-. 19% and 304 .+-. 21%), N-nitrosodimethylamine (NDMA) demethylation (280 .+-. 105% and 228 .+-. 95%), benzene hydroxylation (258 .+-. 60% and 236 .+-. 61%), butanol oxidation (173 .+-. 34% and 154 .+-. 32%), aniline hydroxylation (147 .+-. 22% and 95 .+-. 8%), and ether de-ethylation (95 .+-. 17% and 83 .+-. 17%) and a not significant increase of N-nitrosodiethylamine (NDEA) de-ethylation (34 .+-. 11% and 9 .+-. 8%) in rat microsomes, respectively, versus control animals (mean .+-. SD, values expressed as nmol/min/nmole P-450). All of these activities significantly decreased after 3-MC treatment, except for the p-nitrophenol hydroxylation. PB treatment markedly enhanced NDEA de-ethylation, p-nitrophenol, and benzene hydroxylations (106 .+-. 38%, 109 .+-. 14%, and 153 .+-. 62%, repectively) versus controls. These results suggest that NDMA and especially 1-butanol are the most specific and useful probes of alcohol-inducible cytochrome P-450 in crude liver microsomes.