Abstract
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 (F0–F1 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.
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References
Argese E, Betticol C, Ghelli A, Todescheni R, Miana P (1995) Submitochondrial particles as toxicity biosensors of chlorophenols. Environ Toxicol Chem 14:363–368
Blondin GA, Knobelock LM, Read HW, Harkin JM (1987) Mammalian mitochondria as in vitro monitors of water quality. Bull Environ Contam Toxicol 38:467–474
Brautigan DL, Ferguson-Miller S, Margoliash E (1978) Mitochondrial cytochrome c: preparation and activity of native and chemically modified cytochrome c. Methods Enzymol 53:128–164
Burr R, Schwenk M, Pfaff E (1977) Interaction of Bromosulfophthalein with mitochondrial membranes — uptake of bromosulfophthalein and effect on ANS-fluorescence. Biochem Pharmacol 25:457–460
Castilho RF, Vicente JAF, Kowaltowski A J, Vercesi AE (1997) 4,6-Dinitro-o-cresol uncouples oxidative phosphorylation and induces membrane permeability transition in rat liver mitochondria. Int J Biochem Cell Biol 29:1005–1011
Chance B, Williams GR (1956) The respiratory chain and oxidative phosphorylation. Adv Enzymol 17:65–134
Costantini P, Petronilli V, Colonna R, Bernardi P (1995) On the effects of paraquat on isolated mitochondria. evidence that paraquat causes opening of the cyclosporin-A sensitive permeability transition pore synergistically with nitric oxide (paraquat facilitates the opening of the calcium-dependent permeability transition pore). Toxicology 99:77–88
EPA (US Environmental Protection Agency) (1983) Dicamba. Document 40 CRF 180.227, 21 CRF 193.465 and 561.427, December 28 1983. US EPA, Washington DC
Espandiari P, Thomas VA, Glauert H P, Obrien M, Noonan D, Robertson LW (1995) The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) is a peroxisome proliferator in rats. Fundam Appl Toxicol 26:85–90
Estabrook RW (1967) In: Racker E (ed) Membranes of mitochondria and chloroplasts. Van Nostrand, New York, pp 172–212
Ferreira FML, Madeira VMC, Moreno AJ (1997) Interactions of 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene with mitochondrial oxidative phosphorylation. Biochem Pharmacol 53:299–308
Gazzotti P, Malmstron K, Crompton M (1997) Membrane biochemistry. A laboratory manual on transport and bioenergetics. Springer-Verlag, New York Heidelberg Berlin.
Gornall AG, Bardawill CJ, David MM (1949) Determination of serum proteins by means of the biuret. J Biol Chem 177:751–766
Hallenbeck WH, Cunningham-Burns K M (1985) Pesticides and human health. Springer Verlag, New York Heidelberg Berlin
Kamo N, Muratsugu M, Hongoh R, Kobatake V (1979) Membrane potential of mitochondria measured with an electrode sensitive to tetraphenylphosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state. J Membr Biol 49:105–121
Knobeloch LM, Blondin GA, Read HW, Harkin JM (1990) Assessment of chemical toxicity using mammalian mitochondrial electron transport particles. Arch Environ Contam Toxicol 19:828–835
Lambert CE, Bondy SC (1989) Effects of MPTP, MPP+ and paraquat on mitochondrial potential and oxidative stress. Life Sci 44:1277–1284
Madeira VMC, Antunes-Madeira MC, Carvalho AP (1974) Activation energies of the ATPase activity of sarcoplasmic reticulum. Biochem Biophys Res Commun 58:897–904
Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type mechanism. Nature 191:144–148
Moreno AJM, Madeira VMC (1990) Interference of parathion with mitochondrial bioenergetics. Biochim Biophys Acta 1015:361–267
Moreno AJM, Madeira VMC (1991) Mitochondrial bioenergetics as affected by DDT. Biochim Biophys Acta 1060:166–174
Nicholls DG (1982) Bioenergetics. An introduction to the chemiosmotic theory. Academic Press, London
Palmeira CM, Moreno AJ, Madeira VMC (1994a) Metabolic alterations in hepatocytes promoted by the herbicides paraquat, dinoseb and 2,4-D. Arch Toxicol 68:24–31
Palmeira CM, Moreno AJ, Madeira VMC (1994b). Interactions of herbicides dinoseb and 2,4-D with liver mitochondrial bioenergetics. Toxicol Appl Pharmacol 127:50–57
Palmeira CP, Moreno AJ, Madeira VCM (1995) Mitochondrial bioenergetics is affected by the herbicide paraquat. Biochim Biophys Acta 1229:187–192
Schwenk M, Burr R, Baur H, Pfaff E (1977) Interaction of bromosulfophthalein with mitochondrial membranes: effect on ion movements. Biochem Pharmacol 26:825–832
Singer TP (1974) Determination of the activity of succinate, NADH, choline and α-glycerophosphate dehydrogenases. Methods Biochem Anal 22:123–175
Tisdale HD (1967) Preparation and properties of succinic-cytochrome c reductase (complex II and III). Methods Enzymol 10:213–215
Tomita M (1991) 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). Biochem Pharmacol 42:303–309
Vicente JAF, Santos MS, Vercesi AE, Madeira V MC (1998) Comparative effects of the herbicide dinitro-o-cresol on mitochondrial bioenergetics. Pestic Sci 54:43–51
Vicente JAF, Peixoto F, Lopes ML, Madeira VMC (2001) Differential sensitivities of plant and animal mitochondrial to the herbicide paraquat. J Biochem Mol Toxicol 15:322–330
Videira RA, Antunes-Madeira MC, Custódio JBA, Madeira VMC (1995) Partition of DDE in synthetic and native membranes determined by ultraviolet derivative spectroscopy. Biochim Biophys Acta 1238:22–28
Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482–1488
Wright JP (1994) Use of membrane potential measurements to study mode action of diclofop-methyl. Weed Sci 42:285–292
Acknowledgements
The authors thank Dr. José Almeida from the Veterinary Dept. of UTAD for all the help in the maintenance of animals. This work was supported by the Universidade of Trás-os-Montes e Alto Douro, Vila Real, Portugal. The experiments performed were in comply with the current laws of Portugal.
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Peixoto, F., Vicente, J.A.F. & Madeira, V.M.C. The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) interacts with mitochondrial bioenergetic functions. Arch Toxicol 77, 403–409 (2003). https://doi.org/10.1007/s00204-003-0456-9
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DOI: https://doi.org/10.1007/s00204-003-0456-9