Mahmoud Alaa A A, Abd El-Twab Sanaa M, Alnasser Sulaiman M, Alruhaimi Reem S, Abdel-Moneim Adel, Hassanein Emad H M, Mahmoud Ayman M
Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, 52571, Saudi Arabia.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 23. doi: 10.1007/s00210-025-04465-5.
The pesticide chlorpyrifos (CPF) poses significant environmental and health risks due to its toxicity. Selenium nanoparticles (Se NPs) exhibit promising therapeutic properties. This study evaluated the effects of Se NPs against CPF hepatotoxicity, focusing on oxidative and inflammatory responses, and the SIRT1/FXR/Nrf2 pathway. Rats were exposed to CPF (5.4 mg/kg body weight), with or without Se NPs (0.5 mg/kg body weight), for 28 days, followed by biochemical, histopathological, and molecular analyses. CPF administration significantly increased serum ALT and AST, reduced albumin, and induced histopathological alterations. Se NPs effectively ameliorated liver function biomarkers and mitigated histopathological changes. CPF also elevated malondialdehyde and nitric oxide, and depleted enzymatic antioxidants and GSH, which were mitigated by Se NPs. CPF upregulated NF-κB p65, TNF-α, IL-6, iNOS, Bax and caspase-3, and downregulated Bcl-2. Se NPs suppressed inflammation and apoptosis by downregulating NF-κB p65, pro-inflammatory cytokines and pro-apoptosis markers. These effects were linked to upregulation of SIRT1, FXR, Nrf2 and HO-1 and suppression of Keap1. In conclusion, Se NPs protect against CPF-induced liver injury by attenuating OS, inflammation, and apoptosis, and by upregulating SIRT1//FXR/Nrf2 signaling. These findings highlight the therapeutic potential of Se NPs in mitigating hepatotoxicity induced by exposure to CPF.
农药毒死蜱（CPF）因其毒性对环境和健康构成重大风险。硒纳米颗粒（Se NPs）具有良好的治疗特性。本研究评估了Se NPs对CPF肝毒性的影响，重点关注氧化和炎症反应以及SIRT1/FXR/Nrf2信号通路。将大鼠暴露于CPF（5.4毫克/千克体重），同时或不给予Se NPs（0.5毫克/千克体重），持续28天，随后进行生化、组织病理学和分子分析。给予CPF显著增加了血清谷丙转氨酶（ALT）和谷草转氨酶（AST），降低了白蛋白水平，并诱导了组织病理学改变。Se NPs有效改善了肝功能生物标志物并减轻了组织病理学变化。CPF还升高了丙二醛和一氧化氮水平，消耗了酶促抗氧化剂和谷胱甘肽（GSH），而Se NPs减轻了这些变化。CPF上调了核因子κB p65（NF-κB p65）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、诱导型一氧化氮合酶（iNOS）、促凋亡蛋白Bax和半胱天冬酶-3，并下调了抗凋亡蛋白Bcl-2。Se NPs通过下调NF-κB p65、促炎细胞因子和促凋亡标志物来抑制炎症和凋亡。这些作用与SIRT1、法尼醇X受体（FXR）、核因子E2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的上调以及 Kelch样环氧氯丙烷相关蛋白1（Keap1）的抑制有关。总之，Se NPs通过减轻氧化应激、炎症和凋亡以及上调SIRT1/FXR/Nrf2信号通路来保护大鼠免受CPF诱导的肝损伤。这些发现突出了Se NPs在减轻CPF暴露所致肝毒性方面的治疗潜力。
