Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats

基质金属蛋白酶及其在槲皮素对老年 Zucker 糖尿病肥胖大鼠心脏功能影响机制中的作用

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作者:Barbora Boťanská, Monika Barteková, Kristína Ferenczyová, Mária Fogarassyová, Lucia Kindernay, Miroslav Barančík

Abstract

Several mechanisms may contribute to cardiovascular pathology associated with diabetes, including dysregulation of matrix metalloproteinases (MMPs). Quercetin (QCT) is a substance with preventive effects in treatment of cardiovascular diseases and diabetes. The aim of the present study was to explore effects of chronic QCT administration on changes in heart function in aged lean and obese Zucker Diabetic Fatty (ZDF) rats and that in association with MMPs. Signaling underlying effects of diabetes and QCT were also investigated. In the study, we used one-year-old lean and obese ZDF rats treated for 6 weeks with QCT. Results showed that obesity worsened heart function and this was associated with MMP-2 upregulation, MMP-28 downregulation, and inhibition of superoxide dismutases (SODs). Treatment with QCT did not modulate diabetes-induced changes in heart function and MMPs. However, QCT activated Akt kinase and reversed effects of diabetes on SODs inhibition. In conclusion, worsened heart function due to obesity involved changes in MMP-2 and MMP-28 and attenuation of antioxidant defense by SOD. QCT did not have positive effects on improvement of heart function or modulation of MMPs. Nevertheless, its application mediated activation of adaptive responses against oxidative stress through Akt kinase and prevention of diabetes-induced negative effects on antioxidant defense by SODs.

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