Chlorpyrifos (CPF), considered one of the most potent organophosphates, causes a variety of human disorders including neurotoxicity. The current study was designed to evaluate the efficacy of hesperidin (HSP) in ameliorating CPF-induced neurotoxicity in rats. In the study, rats were treated with HSP (orally, 50 and 100 mg/kg) 30 min after giving CPF (orally, 6.75 mg/kg) for 28 consecutive days. Molecular, biochemical, and histological methods were used to investigate cholinergic enzymes, oxidative stress, inflammation, and apoptosis in the brain tissue. CPF intoxication resulted in inhibition of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) enzymes, reduced antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and elevation of malondialdehyde (MDA) levels and carbonic anhydrase (CA) activities. CPF increased histopathological changes and immunohistochemical expressions of 8-OHdG in brain tissue. CPF also increased levels of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-κB) while decreased levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PGC-1α). Furthermore, CPF increased mRNA transcript levels of caspase-3, Bax, PARP-1, and VEGF, which are associated with apoptosis and endothelial damage in rat brain tissues. HSP treatment was found to protect brain tissue by reducing CPF-induced neurotoxicity. Overall, this study supports that HSP can be used to reduce CPF-induced neurotoxicity.

毒死蜱 (CPF) 被认为是最有效的有机磷酸盐之一，会导致多种人类疾病，包括神经毒性。本研究旨在评估橙皮苷 (HSP) 在改善 CPF 诱导的大鼠神经毒性方面的功效。在这项研究中，连续 28 天给予 CPF（口服，6.75 mg/kg）后 30 分钟，对大鼠进行 HSP（口服，50 和 100 mg/kg）治疗。采用分子、生化和组织学方法研究脑组织中的胆碱能酶、氧化应激、炎症和细胞凋亡。 CPF 中毒导致乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BChE) 酶的抑制，抗氧化状态 [超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GPx) 和谷胱甘肽 (GSH)] 降低，以及丙二醛 (MDA) 升高）水平和碳酸酐酶（CA）活性。 CPF增加了脑组织中8-OHdG的组织病理学变化和免疫组织化学表达。 CPF 还增加了胶质纤维酸性蛋白 (GFAP) 和核因子 kappa B (NF-κB) 的水平，同时降低了核因子红细胞 2 相关因子 2 (Nrf-2)、血红素加氧酶 - 1 (HO-1) 和过氧化物酶体增殖物激活受体 γ 辅激活因子 1 α (PGC-1α)。此外，CPF 增加了 caspase-3、Bax、PARP-1 和 VEGF 的 mRNA 转录水平，这些水平与大鼠脑组织的细胞凋亡和内皮损伤有关。研究发现 HSP 治疗可通过减少 CPF 引起的神经毒性来保护脑组织。总的来说，这项研究支持 HSP 可用于减少 CPF 引起的神经毒性。