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Int. J. Mol. Sci. 2015, 16(4), 8168-8185; doi:10.3390/ijms16048168

Quercetin Improves Postischemic Recovery of Heart Function in Doxorubicin-Treated Rats and Prevents Doxorubicin-Induced Matrix Metalloproteinase-2 Activation and Apoptosis Induction

1
Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia
2
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava 84005, Slovakia
*
Author to whom correspondence should be addressed.
Academic Editor: Chang Won Choi
Received: 27 December 2014 / Revised: 19 March 2015 / Accepted: 24 March 2015 / Published: 13 April 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Quercetin (QCT) is flavonoid that possesses various biological functions including anti-oxidative and radical-scavenging activities. Moreover, QCT exerts some preventive actions in treatment of cardiovascular diseases. The aim of present study was to explore effects of prolonged administration of QCT on changes induced by repeated application of doxorubicin (DOX) in rat hearts. We focused on the ultrastructure of myocardium, matrix metalloproteinases (MMPs), biometric parameters, and apoptosis induction. Our aim was also to examine effects of QCT on ischemic tolerance in hearts exposed to chronic effects of DOX, and to determine possible mechanisms underlying effects of QCT. Our results showed that QCT prevented several negative chronic effects of DOX: (I) reversed DOX-induced blood pressure increase; (II) mediated improvement of deleterious effects of DOX on ultrastructure of left ventricle; (III) prevented DOX-induced effects on tissue MMP-2 activation; and (iv) reversed effects of DOX on apoptosis induction and superoxide dismutase inhibition. Moreover, we showed that rat hearts exposed to effects of QCT were more resistant to ischemia/reperfusion injury. Effects of QCT 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 QCT prevented negative chronic effects of DOX on blood pressure, cellular damage, MMP-2 activation, and apoptosis induction. Moreover, QCT influenced myocardial responses to acute ischemic stress. These facts bring new insights into mechanisms of QCT action on rat hearts exposed to the chronic effects of DOX. View Full-Text
Keywords: quercetin; doxorubicin; heart; ischemic tolerance; matrix metalloproteinases; cell signaling quercetin; doxorubicin; heart; ischemic tolerance; matrix metalloproteinases; cell signaling
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Barteková, M.; Šimončíková, P.; Fogarassyová, M.; Ivanová, M.; Okruhlicová, Ľ.; Tribulová, N.; Dovinová, I.; Barančík, M. Quercetin Improves Postischemic Recovery of Heart Function in Doxorubicin-Treated Rats and Prevents Doxorubicin-Induced Matrix Metalloproteinase-2 Activation and Apoptosis Induction. Int. J. Mol. Sci. 2015, 16, 8168-8185.

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