Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes

Docetaxel-associated liver injury has become a serious public health problem, resulting in therapy discontinuation, liver failure, and death. Zafirlukast is a typical leukotriene receptor antagonist used for prophylaxis and chronic treatment of asthma. In this study, we investigate whether treatment...

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Autores principales:	Ziyi Guo, Xunjin Zeng, Yu Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	zafirlukast docetaxel hepatocytes ldh sirt1 Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/b4312067040944ec822924e11df8ba43
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spelling	oai:doaj.org-article:b4312067040944ec822924e11df8ba432021-12-01T14:41:00ZZafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes2165-59792165-598710.1080/21655979.2021.2005895https://doaj.org/article/b4312067040944ec822924e11df8ba432021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2005895https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Docetaxel-associated liver injury has become a serious public health problem, resulting in therapy discontinuation, liver failure, and death. Zafirlukast is a typical leukotriene receptor antagonist used for prophylaxis and chronic treatment of asthma. In this study, we investigate whether treatment with Zafirlukast could alleviate Docetaxel-induced cytotoxicity in hepatocytes. Our results indicate that Zafirlukast mitigated Docetaxel-induced toxicity in LO-2 hepatocytes. Firstly, Zafirlukast reduced the production of 8-hydroxy-2p-deoxyguanosine (8-OHdG) and increased the levels of reduced glutathione (GSH) against Docetaxel. Secondly, Zafirlukast elevated the levels of mitochondrial membrane potential (ΔΨm) and adenosine triphosphate (ATP). Thirdly, Zafirlukast prevented Docetaxel-induced release of lactate dehydrogenase (LDH) and increased cell viability of LO-2 hepatocytes against Docetaxel. We also found that Zafirlukast ameliorated Docetaxel-induced apoptosis by reducing Caspase-3 and Caspase-9 activity. Mechanistically, our results demonstrate that Zafirlukast inhibited the activation of NOD-like receptor protein 3 (NLRP3), mediated by SIRT1. Based on these findings, we conclude that the administration of Zafirlukast might have a protective effect against Docetaxel-induced cytotoxicity in hepatocytes.Ziyi GuoXunjin ZengYu ZhengTaylor & Francis Grouparticlezafirlukastdocetaxelhepatocytesldhsirt1BiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 11030-11040 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	zafirlukast docetaxel hepatocytes ldh sirt1 Biotechnology TP248.13-248.65
spellingShingle	zafirlukast docetaxel hepatocytes ldh sirt1 Biotechnology TP248.13-248.65 Ziyi Guo Xunjin Zeng Yu Zheng Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes
description	Docetaxel-associated liver injury has become a serious public health problem, resulting in therapy discontinuation, liver failure, and death. Zafirlukast is a typical leukotriene receptor antagonist used for prophylaxis and chronic treatment of asthma. In this study, we investigate whether treatment with Zafirlukast could alleviate Docetaxel-induced cytotoxicity in hepatocytes. Our results indicate that Zafirlukast mitigated Docetaxel-induced toxicity in LO-2 hepatocytes. Firstly, Zafirlukast reduced the production of 8-hydroxy-2p-deoxyguanosine (8-OHdG) and increased the levels of reduced glutathione (GSH) against Docetaxel. Secondly, Zafirlukast elevated the levels of mitochondrial membrane potential (ΔΨm) and adenosine triphosphate (ATP). Thirdly, Zafirlukast prevented Docetaxel-induced release of lactate dehydrogenase (LDH) and increased cell viability of LO-2 hepatocytes against Docetaxel. We also found that Zafirlukast ameliorated Docetaxel-induced apoptosis by reducing Caspase-3 and Caspase-9 activity. Mechanistically, our results demonstrate that Zafirlukast inhibited the activation of NOD-like receptor protein 3 (NLRP3), mediated by SIRT1. Based on these findings, we conclude that the administration of Zafirlukast might have a protective effect against Docetaxel-induced cytotoxicity in hepatocytes.
format	article
author	Ziyi Guo Xunjin Zeng Yu Zheng
author_facet	Ziyi Guo Xunjin Zeng Yu Zheng
author_sort	Ziyi Guo
title	Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes
title_short	Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes
title_full	Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes
title_fullStr	Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes
title_full_unstemmed	Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes
title_sort	zafirlukast ameliorates docetaxel-induced activation of nod-like receptor protein 3 (nlrp3) inflammasome, mediated by sirtuin1 (sirt1) in hepatocytes
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/b4312067040944ec822924e11df8ba43
work_keys_str_mv	AT ziyiguo zafirlukastamelioratesdocetaxelinducedactivationofnodlikereceptorprotein3nlrp3inflammasomemediatedbysirtuin1sirt1inhepatocytes AT xunjinzeng zafirlukastamelioratesdocetaxelinducedactivationofnodlikereceptorprotein3nlrp3inflammasomemediatedbysirtuin1sirt1inhepatocytes AT yuzheng zafirlukastamelioratesdocetaxelinducedactivationofnodlikereceptorprotein3nlrp3inflammasomemediatedbysirtuin1sirt1inhepatocytes
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Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes

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