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Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS

Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin,...

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Autores principales: Wu, Tingni, Ma, Wenxian, Lu, Weili, Huangshen, Zhuofan, Chen, Shiqing, Yang, Qin, Li, Chao, Li, Zeng, Li, Ning, Feng, Xiaowen, Li, Li, Miao, Yu, Wang, Jianan, Liu, Xueqi, Cai, Yuting, He, Yuan, He, Xiaoyan, Li, Jun, Zhao, Ren, Wen, Jiagen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10660019/
https://www.ncbi.nlm.nih.gov/pubmed/38027630
http://dx.doi.org/10.1016/j.heliyon.2023.e21231
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author Wu, Tingni
Ma, Wenxian
Lu, Weili
Huangshen, Zhuofan
Chen, Shiqing
Yang, Qin
Li, Chao
Li, Zeng
Li, Ning
Feng, Xiaowen
Li, Li
Miao, Yu
Wang, Jianan
Liu, Xueqi
Cai, Yuting
He, Yuan
He, Xiaoyan
Li, Jun
Zhao, Ren
Wen, Jiagen
author_facet Wu, Tingni
Ma, Wenxian
Lu, Weili
Huangshen, Zhuofan
Chen, Shiqing
Yang, Qin
Li, Chao
Li, Zeng
Li, Ning
Feng, Xiaowen
Li, Li
Miao, Yu
Wang, Jianan
Liu, Xueqi
Cai, Yuting
He, Yuan
He, Xiaoyan
Li, Jun
Zhao, Ren
Wen, Jiagen
author_sort Wu, Tingni
collection PubMed
description Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin, a chemical entity of flavonoid glycoside, against cisplatin-induced AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were used as the model of cisplatin-induced AKI. The levels of blood urea nitrogen (BUN) and creatine (Cr) levels and periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which was detected by the ICP-MS 6 h after cisplatin injection. Moreover, vaccarin can significantly alleviate the product of reactive oxygen species and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in cisplatin-induced AKI, both in vivo and in vitro. In addition, vaccarin decreased the receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown by the protein levels of cleaved-caspase3 and flow cytometry) and inflammation (shown by the decreased levels of NLRP3, p-P65 and the mRNA of several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) and NOX4 kowndown by siRNA have equivalent protective effect of vaccarin in vitro. When vaccarin was administered together with GLX or NOX4 siRNA, this protective effect of vaccarin did not further increase, as indicating by the index of oxidative stress, cell viability, necroptosis and apoptosis. In conclusion, vaccarin can alleviate cisplatin-induced AKI via inhibiting NOX4.
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spelling pubmed-106600192023-11-02 Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS Wu, Tingni Ma, Wenxian Lu, Weili Huangshen, Zhuofan Chen, Shiqing Yang, Qin Li, Chao Li, Zeng Li, Ning Feng, Xiaowen Li, Li Miao, Yu Wang, Jianan Liu, Xueqi Cai, Yuting He, Yuan He, Xiaoyan Li, Jun Zhao, Ren Wen, Jiagen Heliyon Research Article Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin, a chemical entity of flavonoid glycoside, against cisplatin-induced AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were used as the model of cisplatin-induced AKI. The levels of blood urea nitrogen (BUN) and creatine (Cr) levels and periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which was detected by the ICP-MS 6 h after cisplatin injection. Moreover, vaccarin can significantly alleviate the product of reactive oxygen species and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in cisplatin-induced AKI, both in vivo and in vitro. In addition, vaccarin decreased the receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown by the protein levels of cleaved-caspase3 and flow cytometry) and inflammation (shown by the decreased levels of NLRP3, p-P65 and the mRNA of several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) and NOX4 kowndown by siRNA have equivalent protective effect of vaccarin in vitro. When vaccarin was administered together with GLX or NOX4 siRNA, this protective effect of vaccarin did not further increase, as indicating by the index of oxidative stress, cell viability, necroptosis and apoptosis. In conclusion, vaccarin can alleviate cisplatin-induced AKI via inhibiting NOX4. Elsevier 2023-11-02 /pmc/articles/PMC10660019/ /pubmed/38027630 http://dx.doi.org/10.1016/j.heliyon.2023.e21231 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Wu, Tingni
Ma, Wenxian
Lu, Weili
Huangshen, Zhuofan
Chen, Shiqing
Yang, Qin
Li, Chao
Li, Zeng
Li, Ning
Feng, Xiaowen
Li, Li
Miao, Yu
Wang, Jianan
Liu, Xueqi
Cai, Yuting
He, Yuan
He, Xiaoyan
Li, Jun
Zhao, Ren
Wen, Jiagen
Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS
title Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS
title_full Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS
title_fullStr Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS
title_full_unstemmed Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS
title_short Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS
title_sort vaccarin alleviates cisplatin-induced acute kidney injury via decreasing nox4-derived ros
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10660019/
https://www.ncbi.nlm.nih.gov/pubmed/38027630
http://dx.doi.org/10.1016/j.heliyon.2023.e21231
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