Effect of a single oral dose of methanol, ethanol and propan 2 ol on the hepatic microsomal metabolism of foreign compounds in the rat

Methanol and ethanol administered to rats as a single oral dose increased aniline hydroxylation by the hepatic microsomal fraction by a maximum of 169 and 66% respectively, whereas aminopyrine demethylation was inhibited by 51 and 61%. The concentration of microsomal cytochrome P450, and the activities of NADPH cytochrome c reductase and NADPH cytochrome P450 reductase were unchanged. Propan 2 ol, administered as a single oral dose, increased microsomal aniline hydroxylation by 165% and increased aminopyrine demethylation by 83%. The concentration of cytochrome P450 was unchanged whereas NADPH cytochrome c reductase and NADPH cytochrome P450 reductase were both increased by 38%. Methanol, ethanol and propan 2 ol administration resulted in a decreased type I spectral change, but had no effect on the reverse type I spectral change. Methanol administration decreased the type II spectral change whereas ethanol and propan 2 ol had no effect. Cycloheximide blocked the increases in aniline hydroxylation and aminopyrine demethylation but could not completely prevent the decreases in aminopyrine demethylation. The increases in aniline hydroxylation were due to an increase in V, but Km was unchanged. The ability of acetone to enhance and compound SKF 525A to inhibit microsomal aniline hydroxylation was decreased by the administration of all 3 alcohols. The decrease in the metabolism of aminopyrine may result from a decrease in the binding of the type I site with a consequent failure of aminopyrine to stimulate the reduction of cytochrome P450. Methanol administration may lead to an increase in aniline hydroxylation because of a failure of aniline to inhibit cytochrome P450 reduction.