Induction of heme oxygenase and inhibition of .DELTA.-aminolevulinic acid synthetase of rat liver by thioacetamide and thioacetamide-S-oxide.

Abstract

Thioacetamide and one of its metabolite, thioacetamide-S-oxide, were shown to increase heme oxygenase and to inhibit delta-aminolevulinic acid (ALA) synthetase when administered in vivo to male rats. Concomitant with the increase of heme oxygenase and the decrease of ALA synthetase, concentration of cytochrome P-450 and drug metabolizing enzyme activities were decreased by in vivo administration of thioacetamide and thioacetamide-S-oxide to rats. The results of these studies indicate that thioacetamide and thioacetamide-S-oxide are not only inhibitor of ALA synthetase, but also inducer of heme oxygenase in rats. Further, thioacetamide-S-oxide is generally more effective than thioacetamide with respect to the effects on cytochrome P-450, ALA synthetase and heme oxygenase.