An assessment of the potential of protopine to inhibit microsomal drug metabolising enzymes and prevent chemical-induced hepatotoxicity in rodents.

The potential of protopine to inhibit microsomal drug metabolising enzymes (MDM E) and prevent paracetamol- and CCl4-induced hepatotoxicity was studied in rats. Paracetamol at the dose of 640 mg kg-1 produced hepatic damage in rats as manifested by the rise in serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) to 972+/-186 and 624+/-131 IU (mean+/-sem; n=10), respectively, compared to respective control values of 101+/-29 and 64+/-18 IU. Pretreatment of rats with protopine (11 mg kg-1, orally twice daily for 2 days) lowered significantly the respective serum AST and ALT levels (P<0.05) to 289+/-52 and 178+/-43 IU. The hepatotoxic dose of CCl4 (1.5 ml kg-1; orally) raised serum AST and ALT levels to 543+/-89 and 387+/-69 IU (mean+/-sem; n=10), respectively, compared to respective control values of 98+/-28 and 56+/-17 IU. The same dose of protopine (11 mg kg-1) was able to prevent significantly (P<0.05), the CCl4-induced rise in serum enzymes and the estimated values of AST and ALT were 168+/-36 and 93+/-28 IU, respectively. Protopine caused prolongation (P<0.05) in pentobarbital (55 mg kg-1)-induced sleep as well as potentiated strychnine-induced toxicity in rats, suggestive of an inhibitory effect on MDME. These results indicate that protopine exhibits anti-hepatotoxic action which may be mediated through inhibition of MDME. Copyright 1998 The Italian Pharmacological Society