Quercetin Exerts Age-Dependent Beneficial Effects on Blood Pressure and Vascular Function, But Is Inefficient in Preventing Myocardial Ischemia-Reperfusion Injury in Zucker Diabetic Fatty Rats

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.

Potential Implications of Quercetin and its Derivatives in Cardioprotection

“…It was documented that high-fat diet fed atherosclerotic rats supplemented with extract from the Crataegus pinnatifida (72 and 288 mg/kg) via the intragastric route for 4 weeks had lower plasma levels of lipids (total cholesterol, total triglycerides, LDL-cholesterol, HDL-cholesterol), decreased inflammatory response and inhibited pathological changes in the arteries of atherosclerotic rats suggesting potential of the Crataegus pinnatifida to reduce the development of cardiovascular diseases [108]. On the other hand, our recent study [109] documented different effects of QCT on vasculature and the heart in Diabetes mellitus type 2. In the study, 6-month and 1-year-old male Zucker diabetic fatty rats (ZDF) were daily treated with QCT (20 mg/kg) for 6 weeks.…”

“…In the study, 6-month and 1-year-old male Zucker diabetic fatty rats (ZDF) were daily treated with QCT (20 mg/kg) for 6 weeks. QCT exerted age-dependent beneficial effects on vascular function and blood pressure but was inefficient in preventing myocardial I/R (30 min/2 h) injury in ZDF rats [109].…”

Cardiovascular Changes Related to Metabolic Syndrome: Evidence in Obese Zucker Rats

“…Although there is different data regarding the metabolic alterations in obese rats and the development of cardiac changes [27][28][29], no clear evidence concerning obesity-related oxidative stress and inflammation in the heart is present. Thus, investigating the interplay between these risk factors with obesity/MetS onset as well as the interactions with CVD is fundamental.…”

Improved Survival and Retinal Function of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment

“…There has been few studies that operated with ZDF rats for a long time, for example, for 9 months in some other articles related to diabetic retinopathy, but they measured peripheral blood parameters or carried out histological analyses then (Mishra et al, 2016;Szabo et al, 2017). Cardiovascular function (Ferenczyova et al, 2020) and central nervous system protein changes (Nam et al, 2018) as well as endothelial dysfunction (Vessieres et al, 2013) have been assessed in 12-month-old ZDF animals, and also renal function in 12month-old ZDFxSHHF hybrid rats (Tofovic et al, 2000), but to the best knowledge of the authors of the present article, there are no other articles comprising information about retinal function of ZDF rats diabetic for a whole year, 52 weeks. Similarly, the longest BGP treatment published so far was 12 weeks (3 months) in case of a muscular dystrophy model (Gehrig et al, 2012), and in case of our previous experiments on Goto-Kakizaki rats (Wachal et al, 2020).…”