Demonstration of H₂O₂ production in vivo during aminopyrine metabolism and phenobarbital induction

Abstract

It has been shown previously that, by using methanol and a catalase inhibitor, 3-amino-l, 2,4,-triazole, changes in hepatic H₂O₂ production in vivo can be detected.

Using this method in guinea pigs and rats we could demonstrate increased H₂O₂ production during metabolism in vivo of aminopyrine, especially in phenobarbital-pretreated animals. In contrast, administration of antipyrine does not lead to H₂O₂ production.

In the guinea pigs, phenobarbital induction also stimulates the H₂O₂ production in vivo without administration of exogenous substrates.

The rate and extent of this additional H₂O₂ production depend on the induction state, drug metabolism and species; the major findings are in agreement with and extend previous research in vitro on microsomes, isolated hepatocytes and perfused liver.