Decrease of the in vitro drug-metabolizing activity of the hepatic mixed function oxidase system in rats infected experimentally with Fasciola hepatica: pharmacological implications

Decreases in cytochrome P450-dependent metabolizing activities in the livers of rats inoculated orally with 25 F. hepatica metacercariae were observed up to day 60 of infection. The greatest decrease occurred in the acute stage of infection. These decreases were due to decreased cytochrome P450 and NADPH-cytochrome P450 (cytochrome c) reductase activities. By day 30 of infection their levels were only half of those in controls. By day 60 they had increased to 85 and 90%, respectively, of control values. Cytochrome b5 also changed, but less strikingly (70% of control value on day 30). The depressed drug-metabolizing ability of the liver monooxygenase system might alter the steroids and fatty acids catabolism in the liver, and decrease the safety margin of flukicidal agents detoxified by this system.