Department of Functional Biology and Health Sciences, Faculty of Biology, University of Vigo, Vigo, Spain.
Basic Clin Pharmacol Toxicol. 2009 Dec;105(6):395-400. doi: 10.1111/j.1742-7843.2009.00468.x. Epub 2009 Oct 12.
The effects of different types of pesticides on the in vivo striatal dopamine release were investigated by using in vivo brain microdialysis technique. MPTP, paraquat, maneb, dicofol, DDT, lindane and flutriafol (1 mM) were administered directly into the striatum, and levels of dopamine and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) were measured using HPLC-EC. Intrastriatal administration of pesticides induced the following maximal effects on the dopamine levels: maneb 791 +/- 87%, dicofol 101 +/- 1%, DDT 779 +/- 32%, paraquat 956 +/- 80%, lindane 281 +/- 28% and flutriafol 218 +/- 51% with respect to basal levels. Infusion of pesticides also produced alterations in extracellular DOPAC and HVA levels. A comparative scale of potency was developed to estimate the relative potency of pesticides to induce striatal dopamine release in vivo, using the same concentration and experimental conditions. According to this comparative scale of potency, paraquat is 10 times more potent (in a scale of 10) than dicofol, which did not induce any effect on dopamine release. The second more potent pesticide is maneb, followed by DDT, the organochlorine which has the highest potential to produce alterations on dopaminergic neurotransmission; flutriafol and the organochlorine lindane produced moderate increases in dopamine levels. These results suggest that different classes of pesticides, with different structures and biochemical activities, may affect the striatal dopaminergic system differently, inducing neurotoxicity.
采用活体脑微透析技术研究了不同类型的农药对纹状体多巴胺释放的体内影响。将 MPTP、百草枯、代森锰、三氯杀螨醇、DDT、林丹和氟啶胺（1mM）直接注入纹状体，使用 HPLC-EC 测量多巴胺及其代谢物二羟苯乙酸（DOPAC）和高香草酸（HVA）的水平。纹状体内给予农药引起以下最大的多巴胺水平效应：代森锰 791±87%，三氯杀螨醇 101±1%，DDT 779±32%，百草枯 956±80%，林丹 281±28%和氟啶胺 218±51%，与基础水平相比。农药的输注也导致细胞外 DOPAC 和 HVA 水平的改变。开发了一种比较效力的量表，以估计在相同浓度和实验条件下，农药在体内诱导纹状体多巴胺释放的相对效力。根据这种比较效力的量表，百草枯比三氯杀螨醇（10 倍）强 10 倍（在 10 倍的尺度上），后者对多巴胺释放没有任何影响。第二种更有效的农药是代森锰，其次是 DDT，它是对多巴胺能神经传递产生最大改变的有机氯；氟啶胺和有机氯林丹适度增加了多巴胺水平。这些结果表明，不同结构和生化活性的不同类别的农药可能会以不同的方式影响纹状体多巴胺系统，导致神经毒性。
