Epicatechin breaks preformed glycated serum albumin and reverses the retinal accumulation of advanced glycation end products

Abstract

The accumulation of advanced glycation end products (AGEs) is associated with many of the complications of diabetes mellitus, including diabetic retinopathy. AGE-breakers, such as N-phenacylthiazolium and alagebrium, have been proposed as therapeutic agents for reversing the increase in protein crosslinking in diabetes. (−)-Epicatechin is a major dietary flavonoid with a wide range of health-promoting biological activities. The aim of this study was to determine the potential effect of (−)-epicatechin in reducing the burden of AGEs in vitro and in vivo and to evaluate whether the reduced AGE burden could translate into improvement in retinal vascular function in exogenously AGE-injected rats. Glycated human serum albumin was purified from patients with diabetes. The breakdown of the already formed AGEs was studied by treating glycated human serum albumin with (−)-epicatechin. To study the effect of (−)-epicatechin on retinal vascular function, exogenously AGE-injected rats were treated with (−)-epicatechin (50 and 100mg/kg i.p.) for two weeks. Apoptosis of retinal vascular cells was quantified using TUNEL staining. The AGE load in the retinas was determined via immunohistochemical staining and western blot analysis. (−)-Epicatechin was able to break preformed glycated human serum albumin in vitro as well as reduce AGE accumulation in retinas in vivo in a dose dependent manner. In exogenously AGE-injected rats, treatment with (−)-epicatechin was evidenced by an improved retinal vascular apoptosis. AGE burden in retinas was also reduced upon treatment. This study suggests that (−)-epicatechin could represent a valuable drug for the treatment of diabetic retinopathy by reducing the AGE burden.