NADPH-dependent reaction of paraquat in mouse brain microsomes

When paraquat was incubated with mouse brain microsomes in the presence of NADPH, a Nash-reagent-reactive substance (NRRS) (but not formalin) was produced. It was found that NRRS production was decreased in a dose-dependent manner by N-ethylmaleimide, a sulfhydryl reagent, which also inhibited NADPH-cytochrome P-450 reductase in parallel with the decrease in NRRS production. NRRS production was reduced by radical scavengers (catechin, glutathione, mannitol, superoxide dismutase and catalase), or under anaerobic conditions. In addition, inhibitors of adrenal cortex mitochondrial cytochrome P-450 (metyrapone, aminoglutethimide and amphenone B) inhibited NRRS production without causing a significant decrease in NADPH-cytochrome P-450 reductase activity. These findings suggest that active oxygen species and the mixed-function oxidase system may play important roles in NRRS production from paraquat in brain microsomes.