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

The potential of protopine to inhibit microsomal drug metabolising enz ymes (MDME) and prevent paracetamol- and CCl4-induced hepatotoxicity w as 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 as partate transaminase (AST) and alanine transaminase (ALT) to 972 +/- 1 86 and 624 +/- 131 IU (mean +/- SEM; n = 10), respectively, compared t o respective control values of 101 +/- 29 and 64 +/- 18 IU. Pretreatme nt 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 +/- 189 an d 387 +/- 69 IU (mean +/- SEM; n = 10), respectively, compared to resp ective 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 AS T and ALT were 168 +/- 36 and 93 +/- 28 IU, respectively. Protopine ca used prolongation (P < 0.05) in pentobarbital (55 mg kg(-1))-induced s leep as well as potentiated strychnine-induced toxicity in rats, sugge stive of an inhibitory effect on MDME. These results indicate that pro topine exhibits anti-hepatotoxic action which may be mediated through inhibition of MDME. (C) 1998 The Italian Pharmacological Society.