Prenatal versus neonatal long-term effect of phenobarbital on mouse microsomal drug-oxidizing system

Abstract

Mice were exposed to phenobarbital (PhB) prenatally or neonatally. Prenatal treatment (PreB) was accomplished by feeding the mother PhB, 3 g/kg milled food on gestation days 9-18. Neonates (NeoB mice) were injected daily with 50 mg/kg PhB. The activity of the hepatic microsomal drug-oxidizing system was assayed in the PreB mice (at ages 28 and 50 days), NeoB mice (22, 28 and 50 days) and controls. PreB had at day 28 only small increases in enzyme activity. However, on day 50 there was a 3-fold increase in PhB level compared to control. Among NeoB mice the enzyme activity was 3 times above control on day 22 but the increase was abolished on days 28 and 50. Thus, the long-term increase in the microsomal drug-oxidizing system takes place only after prenatal (and not neonatal) PhB exposure, and the increased enzyme activity occurs around maturity.