Abstract

Acute toxicity of organophosphorus compounds is primarily caused by inhibition of acetylcholinesterase (AChE) at cholinergic synapses. The current study was designed to investigate the effects of paraoxon on histological changes as well as the role of mitochondrion-dependent apoptosis in causing this damage in the rat cerebellum. Adult male Wistar rats were intraperitoneally injected with paraoxon at 0.3, 0.7, or 1 mg/kg. Control animals were injected with corn oil as a vehicle. At 14 or 28 days after intoxication, histological changes and alterations in the expression of apoptosis-related proteins, including Bax, Bcl-2, and caspase-3, were investigated in the cerebellum using cresyl violet staining and western blotting, respectively. Findings showed the decreased thickness of both molecular and granular layers and reduction in the number of Purkinje cells in animals treated with a higher convulsive dose of paraoxon (1 mg/kg). In addition, exposure of rats to 1 mg/kg of paraoxon activated apoptosis pathway confirmed by an increase in Bax and caspase-3 and a decrease in Bcl-2 protein levels. According to our results, cerebellar histological changes and alterations in the expression of apoptosis-related proteins occur following exposure to a high convulsive dose of paraoxon and persist for a long time.

摘要

有机磷化合物的急性毒性主要是由抑制胆碱能突触处的乙酰胆碱酯酶 (AChE) 引起的。目前的研究旨在调查对氧磷对组织学变化的影响以及线粒体依赖性细胞凋亡在引起大鼠小脑损伤中的作用。成年雄性 Wistar 大鼠腹腔注射 0.3、0.7 或 1 mg/kg 的对氧磷。对照动物被注射玉米油作为载体。在中毒后 14 天或 28 天，分别使用甲酚紫染色和蛋白质印迹在小脑中研究了细胞凋亡相关蛋白（包括 Bax、Bcl-2 和 caspase-3）表达的组织学变化和改变。研究结果表明，在接受较高惊厥剂量对氧磷（1 mg/kg）治疗的动物中，分子层和颗粒层的厚度减少，浦肯野细胞数量减少。此外，大鼠暴露于 1 mg/kg 的对氧磷激活的细胞凋亡途径，证实了 Bax 和 caspase-3 的增加以及 Bcl-2 蛋白水平的降低。根据我们的结果，小脑组织学变化和凋亡相关蛋白表达的改变发生在暴露于高惊厥剂量的对氧磷后并持续很长时间。