Effect of Organophosphorus Insecticides on Hepatic Microsomal Cytochrome P-450 in Mice

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A single intraperitoneal injection of fenitrothion (100mg/kg) to mice brought a biphasic effect on microsomal drug metabolism and cytochrome P-450 content. A slight decrease in protoheme was observed, whereas fenitrothion did not affect microsomal Cytochrome b5 content.Pretreatment of mice with SKF 525-A, an inhibitor of drug metabolism, afforded some prevention against the decrease in cytochrome P-450 owing to fenitrothion injection. On the other hand, there was the marked decrease in cytochrome P-450 when some organothiophosphates were incubated with microsomes under the presence of NADPH-generating system in vitro. The decrease was observed as long as organophosphates contained P=S group.These results reveal that the depression of cytochrome P-450 in an earlier stage might be coupled with the oxidative metabolism of sulfur compound. Recovery from the decrease in cytochrome P-450, which ordinary take place within 24hr, was delayed by the concomitant treatment of mice with cobalt chloride indicating that the heme synthesis may be involved in recovery and rebounded increase in cytochrome P-450 in the later stage after the treatment with fenitrothion.
日本農薬学会の論文