AN ASSESSMENT OF THE POTENTIAL OF PROTOPINE TO INHIBIT MICROSOMAL DRUG METABOLISING ENZYMES AND PREVENT CHEMICAL-INDUCED HEPATOTOXICITY IN RODENTS

Abstract

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−1produced 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.