Official journal of the Slovak Society of Cardiology,
Slovak Society of Hypertension and Slovak Association for Cardiac Arrhythmias

Cardiology Letters 2016, 25(4):277-285

Molecular mechanisms of quercetin effects in rats exposed to prolonged doxorubicin administration

Barteková M1, 2, Šimončíková P1, Fogarassyová M1, Okruhlicová L1, Tribulová N1, Radošinská J1, 2, Barančík M1
1 Ústav pre výskum srdca SAV, Bratislava
2 Fyziologický ústav LFUK, Bratislava, Slovenská republika

The natural polyphenolic compound quercetin is a flavonoid that exerts various biological effects including anti-oxidative and radical-scavenging activities. Moreover, quercetin has been shown to possess some preventive actions in treatment of cardiovascular diseases. The aim of the present study was to explore the effects of prolonged administration of quercetin on changes induced by the repeated application of doxorubicin in rat hearts. We focused on the ultrastructure of myocardium, biometric parameters, Akt kinase activity, connexin-43 expression, and apoptosis induction. Our aim was also to examine the effects of quercetin on ischemic tolerance in hearts exposed to chronic effects of doxorubicin, and to determine possible mechanisms underlying the effects of quercetin. Our results showed that quercetin prevented several negative chronic effects of doxorubicin: (I) it reversed doxorubicin-induced blood pressure increase; (II) mediated improvement of deleterious effects of doxorubicin on ultrastructure of left ventricle; and (III) reversed effects of doxorubicin on apoptosis induction. Moreover, we showed that rat hearts exposed to the effects of quercetin were more resistant to ischemia/reperfusion injury. The effects of quercetin on modulation of ischemic tolerance were linked to Akt kinase activation and connexin-43 up-regulation. Taken together, these results demonstrate that prolonged treatment with quercetin prevented the negative chronic effects of doxorubicin on blood pressure, cellular damage, and apoptosis induction. Moreover, quercetin influenced myocardial responses to acute ischemic stress. These facts bring new insights into the mechanisms of quercetin action on rat hearts exposed to the chronic effects of doxorubicin.

Keywords: quercetin; doxorubicin; heart; ischemic tolerance; cell signaling

Published: April 1, 2016  Show citation

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Barteková M, Šimončíková P, Fogarassyová M, Okruhlicová L, Tribulová N, Radošinská J, Barančík M. Molecular mechanisms of quercetin effects in rats exposed to prolonged doxorubicin administration. Cardiology Letters. 2016;25(4):277-285.
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