Targeting oxidative stress, apoptosis, and autophagy by galangin mitigates cadmium-induced renal damage: Role of SIRT1/Nrf2 and AMPK/mTOR pathways

• DOI: 10.1016/j.lfs.2021.120300
• Publication Date: 2022-01-07T01:56:53Z
• Authors: Hany H. Arab; Ahmed M. Ashour; Ahmed H. Eid; El-Shaimaa A. Arafa; Hana J. Al Khabbaz; Sarah A. Abd El-Aal
• Keywords: Galangin

Galangin, a bioactive flavonoid with remarkable antioxidant and anti-apoptotic actions, has demonstrated promising amelioration of experimental hepatotoxicity, cardiomyopathy, and colitis. Yet, its impact on cadmium-induced renal injury has not been explored. Herein, we aimed at exploring the potential of galangin to attenuate cadmium-induced nephrotoxicity in rats, focusing on oxidative stress, apoptosis, and autophagy.Cadmium chloride (5 mg/kg/day) and galangin (15 mg/kg/day) were received by oral gavage and the kidney tissues were inspected using ELISA, biochemical measurements, histology, and immunohistochemistry.Galangin attenuated cadmium-induced renal damage by diminishing the histopathological alterations alongside KIM-1, BUN, and creatinine. At the molecular level, galangin attenuated the oxidative insult by significantly lowering the lipid peroxides and NOX-1 and augmenting GSH and GPx antioxidants. It also activated the cytoprotective SIRT1/Nrf2/HO-1 pathway by significantly upregulating the protein expression of SIRT1, Nrf2, and HO-1. Consistently, galangin suppressed renal apoptotic cell death by significantly lowering the protein expression of Bax and cytochrome C and activity of caspase-3 alongside upregulating the protein expression of the anti-apoptotic Bcl-2. Additionally, galangin activated the impaired autophagy flux as seen by diminishing the accumulation of SQSTM1/p62 and increasing the protein expression of Beclin 1. Meanwhile, galangin stimulated the autophagy-linked AMPK/mTOR pathway by significantly increasing the p-AMPK/total AMPK and lowering p-mTOR/total mTOR ratios.Galangin mitigated cadmium-induced nephrotoxicity thanks to its promising antioxidant, anti-apoptotic, and pro-autophagic effects. In perspective, galangin stimulated the SIRT1/Nrf2/HO-1 and AMPK/mTOR pathways. Hence, it may act as a complementary tool for the management of cadmium-induced renal injury.