Comparison of one-electron reduction activity against the bipyridylium herbicides, paraquat and diquat, in microsomal and mitochondrial fractions of liver, lung and kidney (in vitro).

The first one-electron reduction steps of paraquat and diquat were compared using microsomal and mitochondrial fractions of rat liver, lung and kidney. Both fractions reduced each herbicide effectively, with the order of the Vmax values in microsomes and mitochondria being liver greater than lung greater than kidney and kidney greater than liver greater than lung, respectively. Although similar Vmax values were obtained from the liver and lung with the two subcellular fractions, the affinity of mitochondrial enzymes was lower, suggesting that the reduction of both herbicides in a microsomal site would be dominant in these two organs. The Vmax values for radical formation of paraquat were higher than those of diquat in all the endogenous one-electron reducing systems. The apparent Km values for diquat, however, were lower than those for paraquat in both subcellular fractions from the three tissues, indicating the superiority of the reduction for diquat to that for paraquat at low concentrations. This difference in the Km values supported the finding that the reduction velocity for diquat was significantly higher than that for paraquat at 1 mM concentration. Thus, at low concentrations, diquat would be reduced more easily than paraquat. In addition, tissue enzymatic specificity for paraquat was not obtained. From these data, it seems reasonable to conclude that the tissue-selective accumulation of paraquat previously proposed determines its toxicity.