Incidence of experimental fascioliasis on the activity of drug-metabolizing enzymes in lamb liver.

The purpose of this investigation was to determine the effects of a subclinical fascioliasis at various stages of its development (by week--4, 8, 12, and 16 weeks after the infestation by an oral administration of 150 metacercariae of Fasciola hepatica) on the activity of some hepatic drug-metabolizing systems in lamb. The parasitic pathology was ascertained at autopsy and by clinical observation of animals. Hepatic microsomal cytochrome P-450 content was significantly decreased (by 9-22%) in all infected groups of animals. In early stages of the parasitic disease, decreases in cytochrome b5 content (10-18%) and ethoxycoumarin O-deethylase (25%) were observed, whereas aminopyrine N-demethylase, benzphetamine N-demethylase, and aniline hydroxylase were significantly lowered by 8 to 16 weeks postinfection. Among investigated transferases, glutathione transferase was only decreased (28%) in animals killed 16 weeks after the infestation; in these animals a significant increase in microsomal gamma-glutamyltransferase was observed, probably related to the elevated plasma activity of this enzyme. By 8 weeks postinfection, a simultaneous increase in cytosolic calcium (38%) and decrease in cytosolic glutathione (22%) would correspond to an oxidative cell injury occurring in the course of fascioliasis. The consequences of the fascioliasis-induced decreases in liver-oxidative and conjugative liver drug metabolism are discussed.