1. Voronezh State University, Voronezh, Russia 2. Voronezh State University, Voronezh, Russia; Voronezh State University of Engineering Technologies, Voronezh, Russia
Pesticides represent a serious problem for agricultural workers due to their neurotoxic effects. The aim of this study was to evaluate the ability of pharmacological oxidative phosphorylation uncouplers to reduce the effect of the difenoconazole fungicide on mitochondrial DNA (mtDNA) of various organs in mice. Injections of difenoconazole caused cognitive deficits in mice, and the protonophore 2,4-dinitrophenol (2,4-DNP) and Azur I (AzI), a demethylated metabolite of methylene blue (MB), prevented the deterioration of cognitive abilities in mice induced by difenoconazole. Difenoconazole increased the rate of reactive oxygen species (ROS) production, likely through inhibition of complex I of the mitochondrial respiratory chain. After intraperitoneal administration of difenoconazole lungs, testes and midbrain were most sensitive to the accumulation of mtDNA damage. In contrast, the cerebral cortex and hippocampus were not tolerant to the effects of difenoconazole. The protonophore 2,4-DNP reduced the rate of ROS formation and significantly reduced the amount of mtDNA damage caused by difenoconazole in the midbrain, and partially, in the lungs and testes. MB, an alternative electron carrier capable of bypassing inhibited complex I, had no effect on the effect of difenoconazole on mtDNA, while its metabolite AzI, a demethylated metabolite of MB, was able to protect the mtDNA of the midbrain and testes. Thus, mitochondria-targeted therapy is a promising approach to reduce pesticide toxicity for agricultural workers.
Chernyshova E.V., Potanina D.V., Sadovnikova I.S., Krutskikh E.P., Volodina D.E., Samoylova N.A., Gureev A.P. (2024) The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice. Biomeditsinskaya Khimiya, 70(1), 41-51.
Chernyshova E.V. et al. The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice // Biomeditsinskaya Khimiya. - 2024. - V. 70. -N 1. - P. 41-51.
Chernyshova E.V. et al., "The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice." Biomeditsinskaya Khimiya 70.1 (2024): 41-51.
Chernyshova, E. V., Potanina, D. V., Sadovnikova, I. S., Krutskikh, E. P., Volodina, D. E., Samoylova, N. A., Gureev, A. P. (2024). The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice. Biomeditsinskaya Khimiya, 70(1), 41-51.
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