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Sacubitril/valsartan protects against arsenic trioxide induced cardiotoxicity in vivo and in vitro
- Source :
- Toxicol Res (Camb)
- Publication Year :
- 2022
- Publisher :
- Oxford University Press (OUP), 2022.
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Abstract
- The cardiotoxicity induced by arsenic trioxide (ATO) limits its clinical application in acute promyelocytic leukemia treatment. Sacubitril/valsartan (LCZ696) is an effective drug for the treatment of heart failure. In this study, we aimed to investigate the protective effect and mechanisms of LCZ696 against the ATO-induced cardiotoxicity in mice and H9c2 cells. We found that LCZ696 could alleviate the decrease of ejection fraction and fractional shortening induced by ATO, thereby improving mouse cardiac contractile function. LCZ696 could also reduce the myocardial enzyme, resist oxidative stress, mitigate myocardial fibrosis, and ameliorate myocardial structure, thereby alleviating myocardial damage caused by ATO. In addition, LCZ696 could significantly increase the cell viability and reduce the accumulation of reactive oxygen species in ATO-treated H9c2 cells. Besides, in vivo and in vitro studies have been found that LCZ696 could restore the expression of Bcl-2 and reduce Bax and Caspase-3 levels, inhibiting ATO-induced apoptosis. Meanwhile, LCZ696 decreased the levels of IL-1, IL-6, and TNF-α, alleviating the inflammatory injury caused by ATO. Furthermore, LCZ696 prevented NF-κB upregulation induced by ATO. Our findings revealed that LCZ696 has a considerable effect on preventing cardiotoxicity induced by ATO, which attributes to its capability to suppress oxidative stress, inflammation, and apoptosis.
- Subjects :
- Paper
Health, Toxicology and Mutagenesis
Toxicology
Subjects
Details
- ISSN :
- 20454538
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Toxicology Research
- Accession number :
- edsair.doi.dedup.....91b345c7744e2e7053fdad6193da1a7b