Ameliorative effects of resveratrol against cadmium-induced nephrotoxicity via modulating nuclear xenobiotic receptor response and PINK1/Parkin-mediated Mitophagy

• Published in: Food & function 2020-02, Vol.11 (2), p.1856-1868
• Main Authors: Zhang, Qi, Zhang, Cong, Ge, Jing, Lv, Mei-Wei, Talukder, Milton, Guo, Kai, Li, Yan-Hua, Li, Jin-Long
• Format: Article
• Language: English
• Subjects: Antioxidants; Birds; Cadmium; Damage; Depletion; Detoxification; Gene expression; Hydrogen peroxide; Mitochondria; Mitophagy; Oligonucleotides; Oxidative stress; Parkin protein; Pollutants; PTEN-induced putative kinase; Renal function; Resveratrol; SIRT1 protein; Transcription; Zinc
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c9fo02287b

Cadmium (Cd) is a toxic pollutant with high nephrotoxicity in the agricultural environment. Resveratrol has been found to have a renoprotective effect but the underlying mechanisms of this have not yet been fully elucidated. The aim of this study is to illustrate the antagonism of resveratrol against Cd-induced nephrotoxicity. A total of 80 birds were divided randomly into 4 groups and treated via diet for 90 days as follows: control group (Con); 400 mg kg-1 resveratrol group (Resv); 140 mg kg-1 Cd group (Cd 140); and 140 mg kg-1 Cd + 400 mg kg-1 resveratrol group (Cd + Resv). It was observed that resveratrol treatment dramatically alleviated Cd-induced histopathological lesions of the kidney. Simultaneously, resveratrol mitigated Cd-induced oxidative stress by reducing MDA and H2O2 production, alleviating GSH depletion and restoring the activity of antioxidant enzymes (T-SOD, Cu-Zn SOD, CAT, GST and GSH-Px). Resveratrol activated NXRs (CAR/PXR/AHR/Nrf2) signaling pathways and exerted antidotal roles by enhancing the phase I and II detoxification systems to relieve oxidative damage. Moreover, resveratrol ameliorated Cd-induced ultrastructural abnormality and mitochondria dysfunction by recovering mitochondrial function-related factors VDAC1, Cyt C and Sirt3 upregulation and Sirt1, PGC-1α, Nrf1 and TFAM transcription restrictions. Resveratrol attenuated Cd-induced excessive mitochondrial fission and promoted mitochondrial fusion, which reversed PINK1/Parkin-mediated mitophagy initiation. Collectively, our findings explicate the potential protection against Cd-induced nephrotoxicity and mitochondria damage.