Effects of microsomal enzyme inducers on animals poisoned with hepatotoxins

Abstract

The effects of microsomal enzyme inducers on hepatic function in mice and rats were studied when these drugs were given before or after chemical poisoning. If gastric administration of phetharbital (50–75 mg/kg/day) was begun 12–18 hr after CCl 4 (1.4–1.8 ml/kg) was given, the 20 min sulfobromophthalein (BSP) retention returned to normal in 3–4 days, while animals not receiving the inducer still had markedly abnormal values. SGPT values, which rose after CCl 4, were not affected by phetharbital. The rise in BSP retention after white phosphorus (2–7.5 mg/kg) also returned to normal more rapidly if daily phetharbital followed the administration of the poison. After phosphorus, SGPT did not rise and phetharbital had no effect on the activity of this enzyme. Phenobarbital had the same effect as phetharbital on BSP retention if given after phosphorus, but 3,4-benzpyrene, oxyphenbutazone or cyclizine did not share this effect. No inducer affected mortality or weight gain after phosphorus poisoning of mice. Phenobarbital pretreatment increased mortality after CCl 4 but not after phosphorus.