Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

EFFECTS OF POLYPHENOL QUERCETIN ON SELECTED CARDIOVASCULAR PARAMETERS AND ISCHEMIA-REPERFUSION INJURY OF THE MYOCARDIUM IN RATS WITH TYPE 2 DIABETES K. Ferenczyova 1 , L. Kindernay 1 , B. Kalocayova 1 , M. Sykora 1 , M. Jelemensky 1 , P. Balis 2 , A. Berenyiova 2 , A. Zemancikova 2 , J. Torok 2 , S. Cacanyiova 2 , T. Rajtik 3 , M. Barancik 1 , M. Bartekova 1 1 Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; 2 Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia Quercetin (QCT) is a natural polyphenolic antioxidant that has been studied for its promising cardioprotective potential. In our previous studies QCT exerted cardioprotective effects on ischemia reperfusion (I/R) injury in healthy young animals. The aim of the current study was to reveal potential beneficial cardio- and vasculoprotective effects of QCT in diabetic type 2 rats. QCT (20 mg/kg/day, 6 weeks) was administered to 6-month- and 1-year-old lean (fa/+) and obese (fa/fa) ZDF (Zucker diabetic fatty) rats. Blood pressure was measured by tail-cuff pletysmography before the start and at the end of QCT administration. Isolated perfused hearts were exposed to global I/R (30/120min). Cardiac function was determined by echocardiography in 1-year old ZDF rats. Endothelium-dependent vasorelaxation was measured in isolated aortic rings pre-contracted with phenylephrine (10-6mol/l) followed by application of acetylcholine (10-9 – 10-5mol/l). Molecular mechanisms of QCT effects in the heart were analyzed by Western Blot monitoring protein expression of RISK (Reperfusion Injury Salvage Kinases) signaling pathway. QCT significantly lowered blood pressure in lean and obese 6-month-old ZDF rats but had no effect on blood pressure in 1-year-old rats. Echocardiography revealed that QCT improved diabetes-induced diastolic dysfunction and reduced left ventricular mass. On the other hand, QCT exerted no cardioprotective effect against I/R injury in 6-month-old rats and even worsened post-ischemic recovery of heart function in 1-year-old rats. QCT prevented diabetes-induced impairment of vasorelaxation in obese 6-month-old rats, but accelerated impairment of vasorelaxation in obese 1-year-old rats. QCT had no effect on vasorelaxation in lean rats of both ages. QCT increased eNOS expression in hearts of 6-month-old rats and PKC- ε in 1 -year-old ZDF rats but did not induce global activation of the RISK pathway. QCT appears to have beneficial effects on blood pressure and endothelium-dependent vascular relaxation in type 2 diabetic rats but progression of diabetes and/or ageing may impair these vasculoprotective effects. QCT prevents diabetes-induced diastolic dysfunction and hypertrophy but is ineffective in prevention of cardiac I/R injury in ageing type 2 diabetic rats. QCT ineffectiveness in preventing I/R injury might be due to incomplete activation of RISK pathway, which is considered as one of major signaling pathways of several cardioprotective interventions. Taking together, the presence of comorbidities and ageing might act as confounding factors for beneficial effects of QCT in cardiovascular diseases.

Keywords: quercetin, ischemia-reperfusion injury, endothelium-dependent vasorelaxation, echocardiography, molecular mechanisms

Funding: VEGA grant no 2/0104/20; APVV-18-0548

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