The study of the protective effect of mitochondrial uncouplers during acute toxicity of the fungicide difenoconazole in different organs of mice.

Q3 Biochemistry, Genetics and Molecular Biology
E V Chernyshova, D V Potanina, I S Sadovnikova, E P Krutskikh, D E Volodina, N A Samoylova, A P Gureev
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引用次数: 0

Abstract

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.

研究线粒体解偶联剂在杀菌剂苯醚甲环唑急性毒性作用于小鼠不同器官时的保护作用。
杀虫剂的神经毒性对农业工人来说是一个严重的问题。本研究的目的是评估药理氧化磷酸化解偶联剂降低二唑醇杀菌剂对小鼠各器官线粒体 DNA(mtDNA)影响的能力。注射二唑醇会导致小鼠出现认知障碍,而质子酚 2,4-二硝基苯酚(2,4-DNP)和亚甲基蓝(MB)的脱甲基代谢物 Azur I(AzI)可以防止二唑醇导致的小鼠认知能力退化。地芬诺康唑增加了活性氧(ROS)的产生速度,这可能是通过抑制线粒体呼吸链的复合体 I 实现的。腹腔注射双唑醇后,肺、睾丸和中脑对 mtDNA 损伤的积累最为敏感。相比之下,大脑皮层和海马对苯并唑的影响不耐受。质子拮抗剂 2,4-DNP 可降低 ROS 的形成速度,并显著减少双唑醇在中脑以及部分在肺和睾丸造成的 mtDNA 损伤。MB 是一种能够绕过受抑制的复合体 I 的替代电子载体,它对二苯并唑对 mtDNA 的影响没有影响,而其代谢物 AzI(MB 的一种去甲基化代谢物)则能够保护中脑和睾丸的 mtDNA。因此,线粒体靶向疗法是减少农药对农业工人毒性的一种很有前途的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍: The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).
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