Comparison of Effects of Acetaminophen on Liver Microsomal Drug Metabolism and Lipid Peroxidation in Rats and Mice

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Abstract
The in vivo effect of acetaminophen (AAP), a widely used analgesic, on the lipid peroxidation, drug metabolizing enzyme activity and microsomal electron transfer system of rat and mouse liver was determined. AAP inhibited ethylmorphine N-demethylase activity in the presence of NADPH and this inhibition of the enzyme was due to decrease in cytochrome P-450 content, but not due to change in lipid peroxidation in liver microsomes. Kinetical data showed that AAP administration had no effect on Km values of ethylmorphine N-demethylase; however, a decrease in the Vmax values was seen in rats and mice. There was no significant effect of AAP on both NADPH-cytochrome c reductase and the content of cytochrome b5 3 h after this administration to rats and mice. AAP induced a significant decrease in NADH-ferricyanide reductase in mice, but not in rats. The greatest decrease in cytochrome P-450 was observed among the components of the liver microsomal electron transfer system of rats and mice.