背景:百草枯(PQ),是一种广泛使用的除草剂,是一种公认的强大的神经毒素。然而,其神经毒性的潜在机制仍需进一步研究.
目的:该研究调查了PQ诱导的黑质致密质(SNPC)和小脑神经炎症的发病机理,并评估了硒纳米颗粒(SeN)对这种神经毒性的潜在作用。
方法:36只小鼠随机分为3组,PQ组:小鼠接收10mg/kg的PQ(i。P),和PQ+SeN组;小鼠除口服0.1mg/kgSeN外还接受PQ。所有方案施用14天。小鼠的大脑经过生化处理,分子,组织学,和免疫组织化学评估。
结果:SeN增加了SNPC和小脑抗氧化剂(还原型谷胱甘肽,谷胱甘肽过氧化物酶,和超氧化物歧化酶1),同时降低丙二醛浓度。此外,SeN增加了抗炎白介素(IL)-10,降低了促炎IL-1β和-6,并改善了血管生成一氧化氮和减少了caspase-1。Further,磷酸化Janus激酶(JAK2)/信号转导和转录激活因子3(STAT3)蛋白的蛋白质印迹显示显着下降。SEN对SNPC的改善作用,小脑由显著保存的多巴胺能和浦肯野神经元支持,Luxol快速蓝染色上增强的髓鞘纤维,Olig-2,血小板衍生生长因子-α的显著增加,和酪氨酸羟化酶免疫反应性。
结论:SeN可以通过抗氧化剂减轻PQ诱导的神经毒性,抗炎,和抗凋亡特性。
BACKGROUND: Paraquat (PQ), is an extensively used herbicide and is a well-established powerful neurotoxin. However, the mechanism underlying its neurotoxicity still needs further investigation.
OBJECTIVE: The study investigated the pathogenesis of PQ-induced neuroinflammation of the substantia nigra pars compacta (SNPC) and cerebellum and evaluated the potential effect of selenium nanoparticles (SeN) against such neurotoxicity.
METHODS: Thirty-six mice were randomly divided into three groups; Control group, PQ group: mice received PQ 10 mg/kg (i.p), and PQ + SeN group; mice received PQ in addition to oral SeN 0.1 mg/kg. All regimens were administered for 14 days. The mice\'s brains were processed for biochemical, molecular, histological, and immune-histochemical assessment.
RESULTS: SeN increased the SNPC and cerebellum antioxidants (reduced glutathione, glutathione peroxidase, and superoxide dismutase 1) while decreasing malondialdehyde concentration. Also, SeN increased the anti-inflammatory interleukin (IL)-10 and decreased the pro-inflammatory IL-1β and -6 along with improving the angiogenic nitric oxide and reducing caspase-1. Further, western blots of phosphorylated Janus kinase (JAK2)/signal transducer and activator of transcription3 (STAT3) proteins showed a significant decline. Those improving effects of SeN on SNPC, and cerebellum were supported by the significantly preserved dopaminergic and Purkinje neurons, the enhanced myelin fibers on Luxol fast blue staining, and the marked increase in Olig-2, Platelet-derived growth factor-alpha, and tyrosine hydroxylase immunoreactivity.
CONCLUSIONS: SeN could mitigate PQ-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic properties.