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Ameliorative Effects of Resveratrol against Cadmium-induced Nephrotoxicity via Modulating Nuclear Xenobiotic Receptors Response and PINK1/Parkin-mediated Mitophagy

Abstract

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.

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Article information


Submitted
30 Sep 2019
Accepted
29 Dec 2019
First published
03 Jan 2020

Food Funct., 2020, Accepted Manuscript
Article type
Paper

Ameliorative Effects of Resveratrol against Cadmium-induced Nephrotoxicity via Modulating Nuclear Xenobiotic Receptors Response and PINK1/Parkin-mediated Mitophagy

Q. Zhang, C. Zhang, J. Ge, M. Lv, M. Talukder, K. Guo, L. Yanhua, Y. Zhu and J. Li, Food Funct., 2020, Accepted Manuscript , DOI: 10.1039/C9FO02287B

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