The Effects of the Rat Hepatocarcinogen Methapyrilene HC1 on Hepatic Metabolism in Rats and Mice

Abstract

The effects on the hepatic metabolism of rats and mice of the rat hepatocarcinogen, methapyrilene HC1, were measured using sodium pentobarbital- induced sleeping time (PEN-induced ST) and the in vitro microsomal metabolism of methapyrilene HC1. One month of methapyrilene HC1 treatment in rats prolonged PEN-induced ST and depressed the metabolic activity of the microsomes, indicating a general reduction of the activity of hepatic enzymes. In the mice, however, the methapyrilene 1-IC1 treatment reduced PEN-induced ST and had no effect on the microsomal metabolism. When phenobarbital, a known hepatic enzyme inducer, was administered alone or simultaneously with methapyrilene HC1 in some of the treatment groups, the hepatic enzyme activities in both species were increased. The hepatic enzymes were, therefore, inducible in both species but only the mice were induced by treatment with methapyrilene HC1 alone. The difference in the effects of methapyrilene HC1 on the hepatic detoxifying mechanisms of rats and mice, as indicated by the in vivo metabolism of PEN and the in vitro microsomal metabolism of methapyrilene HC1, may explain the difference between the two species in their susceptibility to the hepatocarcinogenic effects of this compound.