INTERACTIONS OF HERBICIDES 2,4-D AND DINOSEB WITH LIVER MITOCHONDRIALBIOENERGETICS

The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and dinoseb (2-s ec-butyl-4,6-dinitrophenol), were tested in mitochondria because they are putative toxins to the organisms. To understand the toxic mechanis ms involved, we have determined if mitochondrial bioenergetic function s are affected. Dinoseb partially inhibits uncoupled respiration, refl ecting its limited interaction with the mitochondrial redox chain at t he level of succinate dehydrogenase and cytochrome c reductase (comple x III). Additionally, it increased the rate of state 4 oxygen consumpt ion, stimulated ATPase activity, induced permeabilization of membrane mitochondria to H+, and depressed Delta Psi. These data characterize d inoseb as a classical proton uncoupler. The herbicide 2,4-D decreased Delta Psi as a function of concentration and the rate of repolarizatio n was also progressively decreased. State 3 and uncoupled respiration were depressed by approximately the same extent (60%), ruling out inte ractions on phosphorylation assembly independent of the redox chain. T he herbicide strongly inhibited succinate dehydrogenase and cytochrome c reductase (complex III), whereas cytochrome c oxidase was not affec ted. Additionally, 2,4-D also uncoupled mitochondria at concentrations 1000-fold higher than those required for a similar dinoseb effect. Th is study therefore suggests that dinoseb- and 2,4-D-induced cellular d amage, as we have reported before, is putatively preceded by injury up on bioenergetic functions of mitochondria. (C) 1994 Academic Press, In c.