The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) interacts with mitochondrial bioenergetic functions

• Published in: Archives of toxicology 2003-07, Vol.77 (7), p.403-409
• Main Authors: PEIXOTO, Francisco, VICENTE, Joaquim A. F, MADEIRA, Vitor M. C
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Respiration - drug effects; Dicamba - toxicity; Electron Transport Complex IV - metabolism; Energy Metabolism; Herbicides - toxicity; Hydrogen-Ion Concentration; In Vitro Techniques; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondria, Liver - physiology; Mitochondrial Proton-Translocating ATPases - metabolism; Mitochondrial Swelling - drug effects; Mitochondrial Swelling - physiology; Permeability; Pesticides, fertilizers and other agrochemicals toxicology; Proteins; Rats; Rats, Wistar; Succinate Cytochrome c Oxidoreductase - metabolism; Succinate Dehydrogenase - metabolism; Toxicology
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-003-0456-9

The effects of dicamba, a widely used broad-leaf herbicide, on rat liver mitochondrial bioenergetic activities were examined. The results obtained for state 4 respiration indicate not only an uncoupling effect, the result of an increase on the permeability of inner mitochondria membrane to protons, but also a strong inhibitory effect on the redox complexes. State 3 and respiration uncoupled by FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone) were inhibited to approximately the same extent, i.e. by about 70%. Depression of respiratory activity is essentially mediated through partial inhibition of mitochondrial complexes II and III. ATPase activity was much less depressed by dicamba than ATP synthase activity. Therefore, a considerable part of the inhibition observed on ATP synthase is the result of an inhibition on the redox complexes. The loss of phosphorylation capacity, induced by dicamba, was in the last analysis not only the result of a direct effect of dicamba on the enzymatic complex (F(0)-F(1) ATPase) but also the result of a deleterious effect on the integrity of the mitochondrial membrane, which can promote an inhibition of the respiratory complexes and an increase of the proton permeability of the inner membrane.