Attenuation of chlorpyrifos-induced liver injury, oxidative stress and inflammation by selenium nanoparticles via SIRT1/FXR/Nrf2 signaling pathway modulation

Mahmoud, Alaa AA, Abd El-Twab, Sanaa M, Alnasser, Sulaiman M, Alruhaimi, Reem S, Abdel-Moneim, Adel, Hassanein, Emad HM and Mahmoud, Ayman M (2025) Attenuation of chlorpyrifos-induced liver injury, oxidative stress and inflammation by selenium nanoparticles via SIRT1/FXR/Nrf2 signaling pathway modulation. Naunyn-Schmiedeberg's Archives of Pharmacology. ISSN 0028-1298

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Abstract

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.