Modulation of Snake Hepatic Cytochrome P450 by 3-Methylcholanthrene and Phenobarbital

Abstract

Induction mode of the hepatic drug-metabolizing enzymes was studied in Corn snake ( Elaphe guttata emoryi). Treatment of snakes with 3-methylcholanthrene or phenobarbital produced no effects on liver weight and total content of cytochromes P450 and b 5. Treatment with 3-methylcholanthrene significantly induced the activities of arylhydrocarbon hydroxylase, 7-ethoxyresorufin O-deethylase and 7-pentoxyresorufin O-dealkylase, whereas those of ethoxycoumarin O-deethylase, benzphetamine N-demethylase, erythromycin N-demethylase and testosterone hydroxylases were not affected. 3-Methylcholanthrene-induced activities of 7-ethoxyresorufin O-deethylase and 7-pentoxyresorufin O-dealkylase were inhibited by 20 μM α-naphthoflavone by 98% and 73%, respectively. Phenobarbital-treatment caused a significant induction of the activities of erythromycin N-demethylase and testosterone 6 β-hydroxylase, but did not affect those of the other phase I enzymes and the other testosterone hydroxylases. The activities of UDP-glucuronyltransferase and glutathione S-transferase were not affected by either 3-methylcholanthrene or phenobarbital administration. Immunoblotting showed that 3-methylcholanthrene-treatment induced a protein band related to hamster CYP1A2, and decreased the intensity of the two bands detected with anti-rat CYP2B1. Phenobarbital-treatment did not affect the intensity of CYP2B-related proteins. The results suggest that snake liver has multiple forms of cytochrome P450, notably those inducible by 3-methylcholanthrene.