Cardiac effects of advanced glycation end products inhibitor (pyridoxamine) in type 1 diabetic female rats

Abstract

The pharmacologic approaches currently in clinical use have remained unsatisfactory in preventing the cardiac complications associated with diabetes and more innovative therapies are needed. The advanced glycation products (AGEs) formation is an important pathway involved in diabetic cardiomyopathy. In addition, the epicardial adipose tissue (EAT) secretes and expresses adipokines, which have pro- and anti-inflammatory role, and, due to its anatomic characteristics, can modulate cardiac muscle and coronary arteries. Therefore, the aim of this study will be to investigate important proteins involved in cardiac morphological alterations in type 1 diabetic female rats and the effects of co-treatment with insulin + pyridoxamine (inhibitor of AGEs). Additionally, we are going to evaluate the pro- and anti-inflammatory alterations of EAT. Female Wistar rats will be divided in four groups: control (CTR), type 1 DM (DM1, alloxan 170 mg/kg IP), DM1 treated with insulin (DM+INS, 2U morning + 4U evening) and DM1 treated with insulin + pyridoxamine (DM+INS+PDX, 180 mg/kg oral gavage). Circulating factors such as glucose, total cholesterol, triglycerides, glycated A1c hemoglobin, insulin, estradiol and advanced glycation end products-Nµ-carboxymethyllysine (CML), as well as, the protein expressions of AGE, RAGE, Cu/Zn-SOD, Mn-SOD, NOX2, NOX4, NF-kB, GPER (in left ventricle), UCP-1, PGC1-±, adiponectin, leptin, IL-1² and TNF-± (in EAT) will be analyzed. The histological and morphological analyses of heart will be conducted. Tissue reactive oxygen species (ROS) generation will be evaluated. (AU)