Comparative effects of the pyrrolizidine alkaloids jacobine and monocrotaline on hepatic drug metabolising enzymes in the rat.

The effect of i.p. administration of the pyrrolizidine alkaloids jabodine and monocrotaline on the activities of hepatic epoxide hydroase, glutathione S-transferase, aminopyrine N-demethylase and aryl hydrocarbon hydroxylase (AHH) was investigated in young, male Long-Evans rats. Jacobine significantly increased the activities of epoxide hydrase and glutathione S-transferase but caused a reduction of cytochrome P-450 content and in related monooxygenase activities. In contrast, monocrotaline failed to stimulate epoxide hydrase while diminishing the activity of glutathione S-transferase, aminopyrine demethylase and AHH. There was no effect of jacobine or monocrotaline in vitro on the hepatic drug metabolizing enezymes studied except for a slight stimulation of epoxide hydrase activity by jacobine and monocrotaline and a small reduction of aminopyrine demethylase activity by monocrotaline. These results demonstrate that pyrrolizidine alkaloids can have a differential effect on hepatic enzymes depending on the type of alkaloid and the enzyme studied.