The Primary Mode-of-Action of Vinclozolin: Are Oxygen Free Radicals Directly Involved?

Vinclozolin is a dicarboximide fungicide and has been used mainly in the control of diseases caused by Botrytis cinerea and Monilinia spp. Conflicting results have been published concerning the involvement of lipid peroxidation and oxygen free radicals in the mode-ofaction of dicarboximides. The present study was conducted to contribute to this discussion. With emulsions of linolenic acid, in the absence or presence of electron donors (hypoxanthine plus xanthine oxidase or NADPH plus glutathione reductase), vinclozolin caused no significative production of lipid peroxides, as evaluated by the thiobarbituric acid method. In aqueous solutions with hypoxanthine plus xanthine oxidase as electron donors, in B. cinerea cell homogenates with NADH or NADPH, and in actively growing B. cinerea cells, vinclozolin caused no significative production of superoxide, as evaluated by the adrenochrome assay. Positive controls (paraquat and menadione) behaved as expected from data reported in the literature. Three hypotheses were formulated to explain the negative results of this study and the data reported in the literature. (1) The active free radicalproducing species is not the vinclozolin molecule itself but a product of its transformation, resulting, for instance, from active cell metabolism. (2) Lipid peroxides are not directly produced by vinclozolin but are secondary products of vinclozolin activity, for instance, as a consequence of growth arrest. (3) Vinclozolin can induce the formation of oxygen free radicals but by a mechanism different from that operative in toxic xenobiotics, such as quinones, dipyridyls, nitro compounds, and transition metals.