Abstract
Background: Quercetin (QCT) was shown to exert beneficial cardiovascular effects in young healthy animals. The aim of the present study was to determine cardiovascular benefits of QCT in older, 6-month and 1-year-old Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). Methods: Lean (fa/+) and obese (fa/fa) ZDF rats of both ages were treated with QCT for 6 weeks (20 mg/kg/day). Isolated hearts were exposed to ischemia-reperfusion (I/R) injury (30 min/2 h). Endothelium-dependent vascular relaxation was measured in isolated aortas. Expression of selected proteins in heart tissue was detected by Western blotting. Results: QCT reduced systolic blood pressure in both lean and obese 6-month-old rats but had no effect in 1-year-old rats. Diabetes worsened vascular relaxation in both ages. QCT improved vascular relaxation in 6-month-old but worsened in 1-year-old obese rats and had no impact in lean controls of both ages. QCT did not exert cardioprotective effects against I/R injury and even worsened post-ischemic recovery in 1-year-old hearts. QCT up-regulated expression of eNOS in younger and PKCε expression in older rats but did not activate whole PI3K/Akt pathway. Conclusions: QCT might be beneficial for vascular function in diabetes type 2; however, increasing age and/or progression of diabetes may confound its vasculoprotective effects. QCT seems to be inefficient in preventing myocardial I/R injury in type 2 diabetes and/or higher age. Impaired activation of PI3K/Akt kinase pathway might be, at least in part, responsible for failing cardioprotection in these subjects.
Highlights
Quercetin (QCT) is a natural polyphenolic compound widely enriched in human food
We have shown that QCT did not prevent I/R injury in Zucker diabetic fatty (ZDF) rat hearts of both ages as demonstrated by post-ischemic recovery of heart function and infarct size post I/R
We have shown that some proteins of RISK pathway are modulated in ZDF rats due to QCT treatment, up-regulated eNOS in 6-month-old rats and up-regulated PKCε in 1-year-old rats
Summary
Quercetin (QCT) is a natural polyphenolic compound widely enriched in human food. Main sources of QCT are different fruits, vegetables and berries, such as green peppers, red onions, elderberries, red apples, and many others [1,2,3]. QCT has been documented to exert various beneficial effects including neuroprotective [4], cardioprotective [3], anticancer [5], antidiabetic [6], as well as antioxidant [7,8], immunomodulatory and anti-inflammatory effects [1,2]. Cardioprotective effects of QCT were further confirmed by other authors in different models of cardiac I/R injury [13,16,17]. QCT has been shown to exert cardioprotective effects against cardiac I/R injury in streptozotocin-induced diabetic rats, an animal model of diabetes mellitus type 1 [21]. Quercetin (QCT) was shown to exert beneficial cardiovascular effects in young healthy animals. The aim of the present study was to determine cardiovascular benefits of QCT in older, 6-month and 1-year-old Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes)
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