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

Abstract

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.