Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides
Catalysis of catechol oxidation by metal-dithiocarbamate complexes in pesticides
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DOI：
10.1016/s0891-5849(02)01169-3
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发表时间：
2002-12-15
影响因子：
7.4
通讯作者：
Montine, TJ
中科院分区：
文献类型：
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作者：
Fitsanakis, VA;Amarnath, V;Montine, TJ
基于二硫代氨基甲酸酯(DTC)的杀虫剂与帕金森病(PD)风险增加的流行病学联系，职业接触基于DTC的杀虫剂maneb后出现帕金森综合症的临床报告，以及显示大鼠联合暴露于maneb和百草枯的多巴胺能神经退化的实验研究，已被认为与帕金森病(PD)有关。我们推测MANEB中的锰-乙烯-二硫代氨基甲酸酯(MnEBDC)络合物可能通过催化邻苯二酚氧化而产生氧化应激。我们通过对金属-EBDC和金属-二乙基二硫代氨基甲酸酯(DEDC)配合物的结构-功能分析来验证这一假说，以催化N-乙酰多巴胺(NA-DA)和3，4-二羟基苯乙酸(DP)在N-乙酰半胱氨酸(NAC)存在和不存在的情况下氧化N-乙酰多巴胺(NA-DA)和3，4-二羟基苯乙酸(DP)。两种Mn-DTCs都保留了母体离子催化NA-DA单电子氧化的能力，但失去了催化DP氧化的能力。值得注意的是，当锌离子不催化邻苯二酚氧化时，两种锌电极都催化了NA-DA的单电子氧化，而不是对苯二酚。当Cu2+催化氧化这两种邻苯二酚时，CuDTCs是惰性的。MnEBDC和多巴胺或去甲肾上腺素也得到了类似的结果；然而，二硫代氨基甲酸锌对这些儿茶酚的催化氧化效率较低。我们的结果表明，含锰和锌的EBDC杀虫剂有可能促进大脑中儿茶酚胺能区域的氧化应激。(C)2002年爱思唯尔科学公司。
Dithiocarbamate (DTC)-based pesticides have been implicated in Parkinson's disease (PD) through epidemiological links to increased risk of PD, clinical reports of parkinsonism following occupational exposure to the DTC-based pesticide maneb, and experimental studies showing dopaminergic neurodegeneration with combined exposure of rats to maneb and paraquat. We hypothesize that the manganese-ethylene-bis-dithiocarbamate (MnEBDC) complex in maneb may produce oxidative stress by catalyzing catechol oxidation. We tested this hypothesis by performing a structure-function analysis of metal-EBDC and metal-diethyldithiocarbamate (DEDC) complexes of Mn2+, Zn2+, and Cu2+ to catalyze oxidation of N-acetyldopamine (NA-DA) and 3,4-dihydroxyphenyl acetic acid (DP) in the presence and absence of N-acetylcysteine (NAC), a model of glutathione. Both Mn-DTCs retained the capacity of the parent ion to catalyze one-electron oxidation of NA-DA, but lost the ability to catalyze DP oxidation. Strikingly, while Zn2+ did not catalyze catechol oxidation, both Zn-DTCs catalyzed one-electron oxidation of NA-DA but not DP. While Cu2+ catalyzed oxidation of both catechols, Cu-DTCs were inert. Similar results were obtained with MnEBDC and dopamine or norepinephrine; however, zinc-ethylene-bis-dithiocarbamate was less efficient at catalyzing oxidation of these catechols. Our results point to the potential for manganese- and zinc-containing EBDC pesticides to promote oxidative stress in catecholaminergic regions of the brain. (C) 2002 Elsevier Science Inc.