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Zafirlukast ameliorates Docetaxel-induced activation of NOD-like receptor protein 3 (NLRP3) inflammasome, mediated by sirtuin1 (SIRT1) in hepatocytes
- Source :
- Bioengineered, Vol 12, Iss 2, Pp 11030-11040 (2021), Bioengineered, article-version (VoR) Version of Record
- Publication Year :
- 2021
- Publisher :
- Taylor & Francis Group, 2021.
-
Abstract
- 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.
- Subjects :
- Indoles
Inflammasomes
zafirlukast
sirt1
Phenylcarbamates
Bioengineering
Pharmacology
Applied Microbiology and Biotechnology
Cell Line
chemistry.chemical_compound
Sirtuin 1
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Humans
docetaxel
Viability assay
Gene Silencing
Zafirlukast
Receptor
neoplasms
Liver injury
Membrane Potential, Mitochondrial
Sulfonamides
ldh
Cell Death
Leukotriene receptor
Chemistry
General Medicine
Glutathione
medicine.disease
Mitochondria
Oxidative Stress
Apoptosis
Toxicity
hepatocytes
TP248.13-248.65
medicine.drug
Research Article
Research Paper
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 21655987 and 21655979
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Bioengineered
- Accession number :
- edsair.doi.dedup.....6fcb8286691bbc53d031c524b9e8b8ee