title: Quercetin improves postischemic recovery of heart function in doxorubicin-treated rats and prevents doxorubicin-induced matrix metalloproteinase-2 activation and apoptosis induction.
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.
authors: Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia. Monika.Bartekova@savba.sk.
authors: Monika
authors: M
authors: Barteková
authors: Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia. Petra.Simoncikova@savba.sk.
authors: Petra
authors: P
authors: Šimončíková
authors: Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia. maria.fogarassyova@azet.sk.
authors: Mária
authors: M
authors: Fogarassyová
authors: Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia. Monika.Strniskova@savba.sk.
authors: Monika
authors: M
authors: Ivanová
authors: Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia.
authors: Ľudmila
authors: Ľ
authors: Okruhlicová
authors: Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia. Narcisa.Tribulova@savba.sk.
authors: Narcisa
authors: N
authors: Tribulová
authors: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava 84005, Slovakia. Ima.Dovinova@savba.sk.
authors: Ima
authors: I
authors: Dovinová
authors: Institute for Heart Research, Slovak Academy of Sciences, Bratislava 84005, Slovakia. Miroslav.Barancik@savba.sk.
authors: Miroslav
authors: M
authors: Barančík
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018031:Connexin 43; D004317:Doxorubicin; D011794:Quercetin; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2