Alteration of MICE L-tryptophan metabolism by the organophosphorous acid triester diazinon

Abstract

Diazinon [ O, O-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl) phosphorothioate] altered the formation of several l-tryptophan metabolites associated with the l-kynurenine pathway in mice. Liver kynurenine formamidase was inhibited almost completely by diazinon (10 mg/kg). The enzyme inhibition resulted in reduced l-kynurenine biosynthesis in livers with a concomitant accumulation of N- formyl- l- kynurenine . In contrast to the liver, plasma l-kynurenine increased up to 5-fold in diazinon-treated mice. Consequently, the urinary excretion of xanthurenic acid and kynurenic add was raised 5- to 15-fold. The revelation of this novel mechanism of diazinon action is an important piece of information needed for a better understanding of the noncholinergic toxicity of organophosphorous add triesters and methylcarbamates.