Interactions of herbicides 2,4-D and dinoseb with liver mitochondrial bioenergetics.
The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and dinoseb (2-sec-butyl-4,6-dinitrophenol), were tested in mitochondria because they are putative toxins to the organisms. To understand the toxic mechanisms involved, we have determined if mitochondrial bioenergetic functions are affected. Dinoseb partially inhibits uncoupled respiration, reflecting its limited interaction with the mitochondrial redox chain at the level of succinate dehydrogenase and cytochrome c reductase (complex III). Additionally, it increased the rate of state 4 oxygen consumption, stimulated ATPase activity, induced permeabilization of membrane mitochondria to H+, and depressed delta psi. These data characterize dinoseb as a classical proton uncoupler. The herbicide 2,4-D decreased delta psi as a function of concentration and the rate of repolarization was also progressively decreased. State 3 and uncoupled respiration were depressed by approximately the same extent (60%), ruling out interactions on phosphorylation assembly independent of the redox chain. The herbicide strongly inhibited succinate dehydrogenase and cytochrome c reductase (complex III), whereas cytochrome c oxidase was not affected. Additionally, 2,4-D also uncoupled mitochondria at concentrations 1000-fold higher than those required for a similar dinoseb effect. This study therefore suggests that dinoseb- and 2,4-D-induced cellular damage, as we have reported before, is putatively preceded by injury upon bioenergetic functions of mitochondria.
Palmeira
C M
CM
Department of Zoology, University of Coimbra, Portugal.
Moreno
A J
AJ
Madeira
V M
VM
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D004140:Dinitrophenols / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
D004140:Dinitrophenols; D006540:Herbicides; D015084:2,4-Dichlorophenoxyacetic Acid; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; D019297:2,4-Dinitrophenol; C018527:dinoseb