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

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 agains...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Food & function 2020-02, Vol.11 (2), p.1856-1868
Hauptverfasser: Zhang, Qi, Zhang, Cong, Ge, Jing, Lv, Mei-Wei, Talukder, Milton, Guo, Kai, Li, Yan-Hua, Li, Jin-Long
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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.
ISSN:2042-6496
2042-650X
DOI:10.1039/c9fo02287b