Ameliorative Effects of Resveratrol against Cadmium-induced Nephrotoxicity via Modulating Nuclear Xenobiotic Receptors Response and PINK1/Parkin-mediated Mitophagy
Cadmium (Cd) is a toxic pollutant with high nephrotoxicity in agriculture environment. Resveratrol has been expounded a renoprotective effect but the underlying mechanisms of this have not been fully elucidated. The aim of the current study was to illustrate the antagonism of resveratrol against Cd-induced nephrotoxicity. Total 80 birds were divided randomly into 4 groups and treated as follows: control group (Con), 400mg/kg resveratrol group (Resv), 140mg/kg Cd group (Cd 140) and 140 mg/kg Cd+400 mg/kg resveratrol group (Cd+Resv) in diet for 90 days. It was observed that resveratrol treatment dramatically alleviated Cd-induced histopathological lesions of kidney. Simultaneously, resveratrol mitigated Cd-induced oxidative stress by reducing MDA and H2O2 production, alleviating GSH depletion and restoring antioxidant enzymes (T-SOD, Cu-Zn SOD, CAT, GST and GSH-Px) activity. Resveratrol activated NXRs (CAR/PXR/AHR/Nrf2) signaling pathways and exerted antidotal roles by enhanced phase I and II detoxification system to relief oxidative damage. Moreover, resveratrol ameliorated Cd-induced ultrastructural abnormal 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 mitochondria fusion, which rescued PINK1/Parkin-mediated mitophagy initiation. Collectively, our findings explicated a potential protection against Cd-induced nephrotoxicity and mitochondria damage.