Selective inhibition of bipyridyl-stimulated NADPH oxidation by ascorbic acid

The effect of the bipyridyl herbicides, paraquat and diquat (0.01-1.0 mM), on NADPH oxidation was determined in vitro using rat lung microsomal preparations. Experiments were performed in the absence of mixed function oxidation (MFO) substrates, in the presence of substrates (ethylmorphine or benzphetamine), and also in the presence of ascorbic acid (0.1-10.0 mM). NADPH oxidation was stimulated by both herbicides in the absence or presence of either substrate in a concentration-dependent manner. When ascorbic acid was included in incubations along with either bipyridyl, the stimulated rate of NADPH oxidation decreased in the presence of benzphetamine but the stimulation was unaltered in the presence of ethylmorphine or in the absence of substrate. These studies indicate that ascorbic acid may offer some protection from bipyridyl-mediated NADPH oxidation in rat lung microsomal fractions, but that protection appears to be dependent upon the simultaneous presence of specific MFO substrates.