Abstract

SummaryAdministration of nikethamide or phenobarbital to rats increases the rate of degradation of the organophosphorus insecticide, EPN, by a microsomal oxidase system in the liver. Induction of the activity of this system by nikethamide provides a possible explanation for the previously demonstrated ability of this drug to decrease the susceptibility of animals to the acute toxicity of EPN. In the present study there was good correlation between the extent of increase in activity of the detoxification enzyme system by nikethamide and phenobarbital and the ability of these compounds to reduce the acute toxicity of EPN to rats with phenobarbital being superior to nikethamide in both respects. It appears that the microsomal enzyme system that catalyzes the degradation of EPN to p-nitrophenol provides a practical means of testing various chemical agents for ability to induce synthesis of microsomal enzyme activity.

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