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Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprot...

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Autores principales: Zhou, Lu, Yu, Peng, Wang, Ting-ting, Du, Yi-wei, Chen, Yang, Li, Zhen, He, Man-lin, Feng, Lan, Li, Hui-rong, Han, Xiao, Ma, Heng, Liu, Hong-bao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783728/
https://www.ncbi.nlm.nih.gov/pubmed/35075382
http://dx.doi.org/10.1155/2022/9947191
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author Zhou, Lu
Yu, Peng
Wang, Ting-ting
Du, Yi-wei
Chen, Yang
Li, Zhen
He, Man-lin
Feng, Lan
Li, Hui-rong
Han, Xiao
Ma, Heng
Liu, Hong-bao
author_facet Zhou, Lu
Yu, Peng
Wang, Ting-ting
Du, Yi-wei
Chen, Yang
Li, Zhen
He, Man-lin
Feng, Lan
Li, Hui-rong
Han, Xiao
Ma, Heng
Liu, Hong-bao
author_sort Zhou, Lu
collection PubMed
description Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 μM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc(−) inhibitor erastin (10 μM), and the effect of the 40 μM dose of PD was more obvious than that of ferrostatin-1 (1 μM) and deferoxamine (DFO, 100 μM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc(−)-GSH-GPx4 axis and iron metabolism.
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spelling pubmed-87837282022-01-23 Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis Zhou, Lu Yu, Peng Wang, Ting-ting Du, Yi-wei Chen, Yang Li, Zhen He, Man-lin Feng, Lan Li, Hui-rong Han, Xiao Ma, Heng Liu, Hong-bao Oxid Med Cell Longev Research Article Cisplatin is widely used in the treatment of solid tumors, but its application is greatly limited due to its nephrotoxicity; thus, there is still no effective medicine for the treatment of cisplatin-induced acute kidney injury (Cis-AKI). We previously identified that polydatin (PD) exerts nephroprotective effects by antioxidative stress in AKI models. Recent evidence suggests that oxidative stress-induced molecular events overlap with the process of ferroptosis and that there are common molecular targets, such as glutathione (GSH) depletion and lipid peroxidation. Nevertheless, whether the nephroprotective effect of PD is related to anti-ferroptosis remains unclear. In this study, the inhibitory effect of PD on ferroptosis was observed in both cisplatin-treated HK-2 cells (20 μM) in vitro and a Cis-AKI mouse model (20 mg/kg, intraperitoneally) in vivo, characterized by the reversion of excessive intracellular free iron accumulation and reactive oxygen species (ROS) generation, a decrease in malondialdehyde (MDA) content and GSH depletion, and an increase in glutathione peroxidase-4 (GPx4) activity. Remarkably, PD dose-dependently alleviated cell death induced by the system Xc(−) inhibitor erastin (10 μM), and the effect of the 40 μM dose of PD was more obvious than that of ferrostatin-1 (1 μM) and deferoxamine (DFO, 100 μM), classical ferroptosis inhibitors. Our results provide insight into nephroprotection with PD in Cis-AKI by inhibiting ferroptosis via maintenance of the system Xc(−)-GSH-GPx4 axis and iron metabolism. Hindawi 2022-01-15 /pmc/articles/PMC8783728/ /pubmed/35075382 http://dx.doi.org/10.1155/2022/9947191 Text en Copyright © 2022 Lu Zhou et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhou, Lu
Yu, Peng
Wang, Ting-ting
Du, Yi-wei
Chen, Yang
Li, Zhen
He, Man-lin
Feng, Lan
Li, Hui-rong
Han, Xiao
Ma, Heng
Liu, Hong-bao
Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis
title Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis
title_full Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis
title_fullStr Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis
title_full_unstemmed Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis
title_short Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis
title_sort polydatin attenuates cisplatin-induced acute kidney injury by inhibiting ferroptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783728/
https://www.ncbi.nlm.nih.gov/pubmed/35075382
http://dx.doi.org/10.1155/2022/9947191
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