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    Galangin attenuates chlorpyrifos-induced kidney injury by mitigating oxidative stress and inflammation and upregulating Nrf2 and farnesoid-X-receptor in rats

    Alruhaimi, Reem S ORCID logoORCID: https://orcid.org/0000-0003-3746-8582, Ahmeda, Ahmad F ORCID logoORCID: https://orcid.org/0000-0001-5962-9573, Hussein, Omnia E, Alotaibi, Mohammed F, Germoush, Mousa O, Elgebaly, Hassan A, Hassanein, Emad H M ORCID logoORCID: https://orcid.org/0000-0003-4865-2342 and Mahmoud, Ayman M ORCID logoORCID: https://orcid.org/0000-0003-0279-6500 (2024) Galangin attenuates chlorpyrifos-induced kidney injury by mitigating oxidative stress and inflammation and upregulating Nrf2 and farnesoid-X-receptor in rats. Environmental Toxicology and Pharmacology, 110. 104542. ISSN 1382-6689

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    Abstract

    Chlorpyrifos (CPF) is a highly toxic commonly used pesticide and can seriously harm human health. This study assessed the potential of galangin (GAL), an antioxidant flavonoid, to attenuate oxidative stress, inflammation and kidney injury caused by CPF, emphasizing the role of farnesoid-x-receptor (FXR) and Nrf2. Rats were supplemented with CPF and GAL for 28 days. CPF increased serum creatinine, urea and Kim-1, provoked several tissue alterations, and increased kidney ROS, malondialdehyde (MDA), NF-κB p65, TNF-α, iNOS, and caspase-3. GAL effectively ameliorated serum kidney injury markers, ROS, MDA, and TNF-α, suppressed NF-κB p65, iNOS, and caspase-3, and enhanced antioxidants. GAL suppressed Keap1 and upregulated FXR, Nrf2, HO-1 and NQO-1 in CPF-administered rats. GAL exhibited binding affinity with Keap1, FXR, caspase-3, iNOS, HO-1, and NF-κB. In conclusion, GAL is effective in preventing CPF nephrotoxicity by attenuating oxidative stress and inflammation. This protection is linked to upregulation of antioxidants, Nrf2/HO-1 signaling and FXR.

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