Different levels ofSchistosoma mansoniinfection induce changes in drug-metabolizing enzymes

Abstract

AbstractMost carcinogens and xenobiotics are metabolized primarily by the mixed function oxidase system which includes cytochrome P450, cytochrome b5, NADPH-cytochromecreductase and aryl hydrocarbon [benzo(a)pyrene] hydroxylase. The present study investigates the influence of infection with different levels ofSchistosorna mansonicercariae on the hepatic levels of reduced glutathione, glutathione S-transferase and glutathione reductase in addition to the enzymes of mixed function oxidase. Cercariae infection levels of 60, 120, 180, 300 and 600 per mouse increased: (i) the hepatic content of cytochrome P450 by 27%, 38%, 72%, 57%, 48% respectively; (ii) the aryl hydrocarbon hydroxylase activity by 44%, 64%, 76%, 90%, 51% respectively; and (iii) the hepatic level of reduced glutathione by 67%, 83%, 103%, 60%, 38% respectively. The cytochrome b5content did not change at the lowest level of infection but increased at the other four levels by 45%, 76%, 49% and 38% respectively. The activity of glutathione S-transferase increased at the first three levels by 42%, 40%, 27% respectively and decreased at the last two levels by 28% and 52% respectively. On the other hand, the activity of glutathione reductase did not change at any level, whereas, NADPH-cytochromecreductase activity decreased at the last two levels by 44% and 54%. The alterations in the activities of phase I & II of drug-metabolizing enzymes as a result of infection with different levels ofS. mansonimay thus change the liver's capacity to detoxify many endogenous compounds and may also potentiate the deleterious effects of aromatic hydrocarbons, e.g. benzo(a)pyrene, upon the liver and probably other organs. Such alterations may also change the therapeutic actions of drugs that are primarily metabolized by the P450 system, when administered to patients with schistosomiasis.