Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), M. G. Marg, Post Box - 80, Lucknow - 226 001, India Varanasi - 221 005, India.
Curr Neuropharmacol. 2012 Mar;10(1):64-71. doi: 10.2174/157015912799362779.
Cypermethrin, a class II pyrethroid pesticide, is used to control insects in the household and agricultural fields. Despite beneficial roles, its uncontrolled and repetitive applications lead to unintended effects in non-target organisms. Cypermethrin crosses the blood-brain barrier and induces neurotoxicity and motor deficits. Cypermethrin prolongs the opening of sodium channel, a major site of its action, leading to hyper-excitation of the central nervous system. In addition to sodium channel, cypermethrin modulates chloride, voltage-gated calcium and potassium channels, alters the activity of glutamate and acetylcholine receptors and adenosine triphosphatases and induces DNA damage and oxidative stress in the neuronal cells. Cypermethrin also modulates the level of neurotransmitters, including gamma-aminobutyric acid and dopamine. It is one of the most commonly used pesticides in neurotoxicology research not only because of its variable responses depending upon the doses, time and routes of exposure and strain, age, gender and species of animals used across multiple studies but also owing to its ability to induce the nigrostriatal dopaminergic neurodegeneration. This article describes the effect of acute, chronic, developmental and adulthood exposures to cypermethrin in experimental animals. The article sheds light on cypermethrin-induced changes in the central nervous system, including its contribution in the onset of specific features, which are associated with the nigrostriatal dopaminergic neurodegeneration. Resemblances and dissimilarities of cypermethrin-induced nigrostriatal dopaminergic neurodegeneration with sporadic and chemicals-induced disease models along with its advantages and pitfalls are also discussed.
氯菊酯，一种 II 类拟除虫菊酯农药，用于控制家庭和农业领域的昆虫。尽管具有有益作用，但它的无控制和重复应用会导致非目标生物产生意外影响。氯菊酯穿过血脑屏障，引起神经毒性和运动缺陷。氯菊酯延长钠离子通道的开放，这是其作用的主要部位，导致中枢神经系统过度兴奋。除了钠离子通道，氯菊酯还调节氯离子、电压门控钙和钾通道，改变谷氨酸和乙酰胆碱受体以及三磷酸腺苷酶的活性，并在神经元细胞中诱导 DNA 损伤和氧化应激。氯菊酯还调节神经递质的水平，包括γ-氨基丁酸和多巴胺。它是神经毒理学研究中最常用的农药之一，不仅因为其在不同剂量、时间和暴露途径以及不同研究中使用的动物品系、年龄、性别和物种中的反应具有可变性，还因为其诱导黑质纹状体多巴胺能神经退行性变的能力。本文描述了急性、慢性、发育和成年期暴露于实验动物的氯菊酯的影响。本文揭示了氯菊酯对中枢神经系统的影响，包括其对特定特征的发病机制的贡献，这些特征与黑质纹状体多巴胺能神经退行性变有关。还讨论了氯菊酯诱导的黑质纹状体多巴胺能神经退行性变与散发性和化学物质诱导疾病模型的相似性和差异性，以及其优点和缺陷。
