Department of Functional Biology and Health Sciences, University of Vigo, Spain.
Department of Functional Biology and Health Sciences, University of Vigo, Spain.
Pestic Biochem Physiol. 2022 Mar;182:105035. doi: 10.1016/j.pestbp.2022.105035. Epub 2022 Jan 7.
Although the toxic effects of organophosphorus (OP) pesticides have been classically attributed to inhibition of the acetylcholinesterase, other neurotoxic mechanisms, as oxidative stress can also occur. Here we evaluated if antioxidants prevent the excessive dopamine release induced by OP pesticides in conscious and freely moving rats, using cerebral microdialysis technique. Intrastriatal infusion of paraoxon (5 mM), glufosinate (10 mM) or glyphosate (5 mM) significantly increased the dopamine release (1006 ± 106%, 991 ± 142%, and 1164 ± 128%, relative to baseline, respectively). To evaluate if these increased dopamine release could be related to oxidative stress, we pretreated animals with antioxidants glutathione (GSH, 400 or 800 μM), dithiothreitol (DTT, 5 or 10 μM), trolox (1 or 3 mM), and α-lipoic acid (ALA, 400 or 800 μM) before administration of OP pesticides. Intrastriatal administration of the antioxidants GSH, DTT, trolox, and ALA was highly effective in preventing the glyphosate and glufosinate-induced dopamine overflow. However, only GSH (800 μM) significantly decreased the effect of paraoxon on dopamine levels. The high toxicity of this pesticide and the low concentrations used could explain this lack of effect in our experimental conditions. The fact that ROS scavengers prevent the excessive dopamine release induced by OP pesticides, further supports the view that dopamine overflow can cause neuronal damage mediated, at least in part, by oxidative stress.
虽然有机磷（OP）农药的毒性作用经典地归因于乙酰胆碱酯酶的抑制，但其他神经毒性机制，如氧化应激也可能发生。在这里，我们使用脑微透析技术评估抗氧化剂是否可以预防 OP 农药在清醒和自由活动的大鼠中引起的多巴胺过度释放。纹状体内输注对氧磷（5 mM）、草甘膦（10 mM）或草铵膦（5 mM）可显著增加多巴胺释放（相对于基线分别增加 1006±106%、991±142%和 1164±128%）。为了评估这些增加的多巴胺释放是否与氧化应激有关，我们在给予 OP 农药前用抗氧化剂谷胱甘肽（GSH，400 或 800 μM）、二硫苏糖醇（DTT，5 或 10 μM）、trolox（1 或 3 mM）和 α-硫辛酸（ALA，400 或 800 μM）预处理动物。纹状体内给予抗氧化剂 GSH、DTT、trolox 和 ALA 可有效预防草甘膦和草铵膦诱导的多巴胺溢出。然而，只有 GSH（800 μM）显著降低了对氧磷对多巴胺水平的影响。这种农药的高毒性和使用的低浓度可能解释了我们实验条件下缺乏这种作用的原因。ROS 清除剂可预防 OP 农药引起的多巴胺过度释放这一事实进一步支持了这样一种观点，即多巴胺溢出可能导致神经元损伤，至少部分是由氧化应激介导的。
