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: https://orcid.org/0000-0003-3746-8582, Ahmeda, Ahmad F ORCID: https://orcid.org/0000-0001-5962-9573, Hussein, Omnia E, Alotaibi, Mohammed F, Germoush, Mousa O, Elgebaly, Hassan A, Hassanein, Emad H M ORCID: https://orcid.org/0000-0003-4865-2342 and Mahmoud, Ayman M ORCID: 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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Official URL: http://dx.doi.org/10.1016/j.etap.2024.104542

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.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	23 Sep 2024 10:57
Publisher:	Elsevier
Additional Information:	This paper was accepted for publication in the journal Environmental Toxicology and Pharmacology and the definitive published version is available at http://dx.doi.org/10.1016/j.etap.2024.104542
Divisions:	Faculties > Science and Engineering Faculties > Science and Engineering > Department of Life Science
Subject terms:	Kidney, Animals, Rats, Rats, Wistar, Inflammation, Chlorpyrifos, Flavonoids, Receptors, Cytoplasmic and Nuclear, Antioxidants, Insecticides, Up-Regulation, Oxidative Stress, Male, NF-E2-Related Factor 2, Acute Kidney Injury, Farnesoid-x-receptor, Flavonoids, Nephrotoxicity, Oxidative stress, Pesticides, Animals, Oxidative Stress, NF-E2-Related Factor 2, Chlorpyrifos, Male, Flavonoids, Up-Regulation, Kidney, Receptors, Cytoplasmic and Nuclear, Rats, Inflammation, Insecticides, Antioxidants, Rats, Wistar, Acute Kidney Injury, 0502 Environmental Science and Management, 1115 Pharmacology and Pharmaceutical Sciences, Toxicology, 3214 Pharmacology and pharmaceutical sciences, 4104 Environmental management, 4105 Pollution and contamination
Data Access Statement:	The manuscript contains all data supporting the reported results.
URI:	https://e-space.mmu.ac.uk/id/eprint/635739
DOI:	https://doi.org/10.1016/j.etap.2024.104542
ISSN	1382-6689
e-ISSN	1872-7077

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