Drug Development Research | 2021
Targeting AGE‐RAGE signaling pathway by Saxagliptin prevents myocardial injury in isoproterenol challenged diabetic rats
Abstract
The role of Saxagliptin in diabetes‐associated cardiovascular complications is controversial. This study aimed to investigate whether Saxagliptin could prevent Isoproterenol‐induced myocardial changes in diabetic rats and to identify the possible mechanism as well. The high‐fat diet/low‐dose Streptozotocin‐induced type 2 diabetic rats were divided into 3 groups: the control group (0.25% CMC for 28\u2009days), the Isoproterenol group (85\u2009mg/kg Isoproterenol for the last 2\u2009days plus 0.25% CMC for 28\u2009days), and the treatment group (10\u2009mg/kg Saxagliptin for 28\u2009days plus 85\u2009mg/kg Isoproterenol for the last 2\u2009days). Hemodynamic measurements were performed, and samples were examined for RAGE and NF‐κB expressions, histopathological and ultrastructural changes, AGEs level, myocardial injury markers, oxidative stress, and apoptosis. Saxagliptin significantly recovered cardiac function (p\u2009<\u2009.001), reverted myocardial injury and oxidative stress levels back to the control value (p\u2009<\u2009.05 to p\u2009<\u2009.001). Saxagliptin alleviates Isoproterenol‐induced myocardial injury in diabetic rats by suppressing AGE‐RAGE pathway.