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Trimetazidine ameliorates sunitinib-induced cardiotoxicity in mice via the AMPK/mTOR/autophagy pathway.


ABSTRACT: Context: Sunitinib (SU) is a multi-targeted tyrosine kinase inhibitor anticancer agent whose clinical use is often limited by cardiovascular complications. Trimetazidine (TMZ) is an anti-angina agent that has been demonstrated cardioprotective effects in numerous cardiovascular conditions, but its potential effects in SU-induced cardiotoxicity have not been investigated. Objective: This study investigates the effect of TMZ in sunitinib-induced cardiotoxicity in vivo and in vitro and molecular mechanisms. Materials and methods: Male 129S1/SvImJ mice were treated with vehicle, SU (40?mg/kg/d) or SU and TMZ (20?mg/kg/d) via oral gavage for 28?days, and cardiovascular functions and cardiac protein expressions were examined. H9c2 cardiomyocytes were treated with vehicle, SU (2-10??M) or SU and TMZ (40-120??M) for 48?h, and cell viability, apoptosis, autophagy, and protein expression was tested. Results: SU induces hypertension (systolic blood pressure [SBP]?+?28.33?±?5.00?mmHg) and left ventricular dysfunction (left ventricular ejection fraction [LVEF]?-?11.16?±?2.53%) in mice. In H9c2 cardiomyocytes, SU reduces cell viability (IC50 4.07??M) and inhibits the AMPK/mTOR/autophagy pathway (p?

SUBMITTER: Yang Y 

PROVIDER: S-EPMC6764339 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Trimetazidine ameliorates sunitinib-induced cardiotoxicity in mice via the AMPK/mTOR/autophagy pathway.

Yang Yi Y   Li Na N   Chen Tongshuai T   Zhang Chunmei C   Liu Lingxin L   Qi Yan Y   Bu Peili P  

Pharmaceutical biology 20191201 1


<b>Context:</b> Sunitinib (SU) is a multi-targeted tyrosine kinase inhibitor anticancer agent whose clinical use is often limited by cardiovascular complications. Trimetazidine (TMZ) is an anti-angina agent that has been demonstrated cardioprotective effects in numerous cardiovascular conditions, but its potential effects in SU-induced cardiotoxicity have not been investigated. <b>Objective:</b> This study investigates the effect of TMZ in sunitinib-induced cardiotoxicity <i>in vivo</i> and <i>i  ...[more]

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