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Exposure to the environmentally relevant fungicide Maneb: Studying toxicity in the soil nematode Caenorhabditis elegans
Environment International ( IF 10.3 ) Pub Date : 2023-12-06 , DOI: 10.1016/j.envint.2023.108372 Laura Kubens 1 , Ann-Kathrin Weishaupt 2 , Vivien Michaelis 3 , Isabelle Rohn 4 , Fabian Mohr 5 , Julia Bornhorst 2
Environment International ( IF 10.3 ) Pub Date : 2023-12-06 , DOI: 10.1016/j.envint.2023.108372 Laura Kubens 1 , Ann-Kathrin Weishaupt 2 , Vivien Michaelis 3 , Isabelle Rohn 4 , Fabian Mohr 5 , Julia Bornhorst 2
Affiliation
Maneb is a manganese-containing ethylene bisdithiocarbamate fungicide and is still commonly used as no cases of resistance have been documented. However, studies have shown that Maneb exposure has neurodegenerative potential in mammals, resulting in symptoms affecting the motor system. Despite its extensive use, structural elucidation of Maneb has only recently been accomplished by our group. This study aimed to examine the bioavailability of Maneb, the quantification of oxidative stress-related endpoints and neurotransmitters employing pure Maneb, its metabolites and structural analogues, in the model organism Caenorhabditis elegans . Exposure to Maneb did not increase the bioavailability of Mn compared to manganese chloride, although Maneb was about 8 times more toxic with regard to lethality. Maneb generated not significantly reactive oxygen and nitrogen species (RONS) but decreased the ATP level while increasing the amount of glutathione and its oxidized form in a dose-dependent manner. Nevertheless, an alteration in the neurotransmitter homeostasis of dopamine, acetylcholine, and gamma-butyric acid (GABA) was observed as well as morphological changes in the dopaminergic neurons upon Maneb exposure, which underlines the assumption of the neurotoxic potential of Maneb. This study showed that Maneb exhibits effects based on a combined interaction of the ligand and manganese.
中文翻译:
暴露于环境相关杀菌剂 Maneb:研究土壤线虫 Caenorhabditis elegans 的毒性
Maneb 是一种含锰的乙烯二二硫代氨基甲酸酯杀菌剂,由于没有耐药性案例的记录,因此仍然被广泛使用。然而,研究表明,Maneb 暴露在哺乳动物中具有神经退行性潜力,导致影响运动系统的症状。尽管 Maneb 用途广泛,但我们小组直到最近才完成了 Maneb 的结构阐明。本研究旨在检查模式生物秀丽隐杆线虫中 Maneb 的生物利用度、氧化应激相关终点和采用纯 Maneb、其代谢物和结构类似物的神经递质的定量。与氯化锰相比,暴露于 Maneb 并没有增加 Mn 的生物利用度,尽管 Maneb 的致死毒性大约高 8 倍。Maneb 不产生显着的活性氧和氮物质 (RONS),但降低了 ATP 水平,同时以剂量依赖性方式增加了谷胱甘肽及其氧化形式的量。然而,在 Maneb 暴露后观察到多巴胺、乙酰胆碱和 γ-丁酸 (GABA) 的神经递质稳态发生变化以及多巴胺能神经元的形态变化,这强调了 Maneb 神经毒性潜力的假设。这项研究表明,Maneb 表现出基于配体和锰的联合相互作用的效果。
更新日期:2023-12-06
中文翻译:
暴露于环境相关杀菌剂 Maneb:研究土壤线虫 Caenorhabditis elegans 的毒性
Maneb 是一种含锰的乙烯二二硫代氨基甲酸酯杀菌剂,由于没有耐药性案例的记录,因此仍然被广泛使用。然而,研究表明,Maneb 暴露在哺乳动物中具有神经退行性潜力,导致影响运动系统的症状。尽管 Maneb 用途广泛,但我们小组直到最近才完成了 Maneb 的结构阐明。本研究旨在检查模式生物秀丽隐杆线虫中 Maneb 的生物利用度、氧化应激相关终点和采用纯 Maneb、其代谢物和结构类似物的神经递质的定量。与氯化锰相比,暴露于 Maneb 并没有增加 Mn 的生物利用度,尽管 Maneb 的致死毒性大约高 8 倍。Maneb 不产生显着的活性氧和氮物质 (RONS),但降低了 ATP 水平,同时以剂量依赖性方式增加了谷胱甘肽及其氧化形式的量。然而,在 Maneb 暴露后观察到多巴胺、乙酰胆碱和 γ-丁酸 (GABA) 的神经递质稳态发生变化以及多巴胺能神经元的形态变化,这强调了 Maneb 神经毒性潜力的假设。这项研究表明,Maneb 表现出基于配体和锰的联合相互作用的效果。