Rosmarinic acid mitigates chlorpyrifos-induced oxidative stress, inflammation, and kidney injury in rats by modulating SIRT1 and Nrf2/HO-1 signaling

• Published in: Life sciences (1973) 2023-01, Vol.313, p.121281, Article 121281
• Main Authors: Abduh, Maisa Siddiq, Alruhaimi, Reem S., Alqhtani, Haifa A., Hussein, Omnia E., Abukhalil, Mohammad H., Kamel, Emadeldin M., Mahmoud, Ayman M.
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - metabolism; Animals; Antioxidants - metabolism; Chlorpyrifos - toxicity; Cinnamates - pharmacology; Cinnamates - therapeutic use; Depsides - pharmacology; Depsides - therapeutic use; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Kelch-Like ECH-Associated Protein 1 - metabolism; Kidney - drug effects; Kidney - pathology; Molecular Docking Simulation; Nephrotoxicity; NF-E2-Related Factor 2 - drug effects; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Organophosphorus pesticides; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Rosmarinic Acid; Sirtuin 1 - drug effects; Sirtuin 1 - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.121281

Chlorpyrifos (CPF) is a widely used broad-spectrum pesticide with multi-organ toxic effects. Oxidative stress was found to play a role in the deleterious effects of CPF, including nephrotoxicity. This study investigated the protective effect of the antioxidant polyphenol rosmarinic acid (RA) against CPF-induced kidney injury, with an emphasis on oxidative injury, inflammation, SIRT1, and Nrf2/HO-1 signaling. Rats received 10 mg/kg CPF and 25, 50, and 100 mg/kg RA orally for 28 days, and the samples were collected for analysis. CPF increased serum urea and creatinine and kidney Kim-1 and caused several histopathological alterations. ROS, MDA, NO, NF-κB p65, TNF-α, and IL-1β were elevated in the kidney of CPF-intoxicated rats. RA ameliorated kidney function markers, prevented tissue injury, suppressed ROS, MDA, and NO, and downregulated NF-κB p65, TNF-α, and IL-1β in CPF-intoxicated rats in a dose-dependent manner. RA decreased Bax, caspase-3, oxidative DNA damage, and Keap1, boosted antioxidant enzymes and Bcl-2, and upregulated Nrf2, HO-1, and SIRT1 in CPF-administered rats. Molecular docking simulation revealed the binding affinity of RA toward NF-κB, Keap1, HO-1, and SIRT1. In conclusion, RA prevented CPF nephrotoxicity by attenuating oxidative stress, inflammation, and apoptosis and upregulating SIRT1 and Nrf2/HO-1 signaling. •Chlorpyrifos induces oxidative stress, inflammation, and kidney injury.•Rosmarinic acid attenuates chlorpyrifos-induced ROS and inflammation.•Rosmarinic acid upregulates Nrf2/HO-1 signaling in chlorpyrifos-administered rats.•Rosmarinic acid inhibits NF-κB and apoptosis, and upregulates SIRT1.