Division of Pharmacology and Toxicology, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
Neurochem Res. 2012 May;37(5):1102-11. doi: 10.1007/s11064-012-0715-3. Epub 2012 Feb 14.
Chronic exposure to agricultural chemicals (pesticides/herbicides) has been shown to induce neurotoxic effects or results in accumulation of various toxic metabolic by-products. These substances have the relevant ability to cause or increase the risk for neurodegeneration. Diquat is an herbicide that has been extensively used in the United States of America and other parts of the world. Diquat is constantly released into the environment during its use as a contact herbicide. Diquat structurally resembles 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and paraquat. Rotenone, paraquat, maneb and MPTP reproduce features of movement disorders in experimental animal models. Based on the structural similarity to other neurotoxins, chronic exposure of diquat can induce behavioral and neurochemical alterations associated with dopaminergic neurotoxicity. However, in the present study, diquat unlike other neurotoxins (rotenone, 6-hydroxydopamine, MPTP, paraquat and maneb) did not induce dopamine depletion in the mouse striatum. Although, notable exacerbation in motor impairment (swimming score, akinesia and open field) were evident that may be due to the decreased dopamine turnover and mild nigrostriatal neurodegeneration. These data indicate that, despite the apparent structural similarity to other dopaminergic neurotoxins, diquat did not exert severe deleterious effects on dopamine neurons in a manner that is unique to rotenone and MPTP.
慢性暴露于农业化学品(杀虫剂/除草剂)已被证明会引起神经毒性作用或导致各种有毒代谢副产物的积累。这些物质具有引起或增加神经退行性变风险的相关能力。百草枯是一种在美国和世界其他地区广泛使用的除草剂。百草枯在用作接触性除草剂时会不断释放到环境中。百草枯在结构上类似于 1-甲基-4-苯基-1,2,3,6 四氢吡啶(MPTP)和百草枯。鱼藤酮、百草枯、代森锰和 MPTP 在实验动物模型中再现运动障碍的特征。基于与其他神经毒素的结构相似性,慢性暴露于百草枯会引起与多巴胺能神经毒性相关的行为和神经化学改变。然而,在本研究中,与其他神经毒素(鱼藤酮、6-羟多巴胺、MPTP、百草枯和代森锰)不同,百草枯不会导致小鼠纹状体中的多巴胺耗竭。尽管运动障碍(游泳评分、运动不能和旷场试验)明显加重,但这可能是由于多巴胺周转率降低和轻度黑质纹状体神经退行性变所致。这些数据表明,尽管与其他多巴胺能神经毒素在结构上明显相似,但百草枯不会以类似于鱼藤酮和 MPTP 的方式对多巴胺神经元产生严重的有害影响。