Partially protective effect of telmisartan on slow healing wounds in diabetic rats: possible role of AGEs-RAGE axis

Abstract

Accumulation of advanced glycation endproducts (AGEs) has been found in healthy aging persons and during elevated glucose concentrations. It has been implicated in microvascular and macrovascular damage and delayed wound healing associated with diabetes, presumably through vascular, neurological, or intermediary metabolic modifications. The aim of the present work is to examine the potentially protective effect of telmisartan against diabetes-induced peripheral neuropathy in rats. Diabetic rats (Streptozotocin, STZ 50 mg/kg) were treated with vehicle or telmisartan (5 mg/kg) for 8 weeks. Behavioural tests (footprint and hotplate) were performed every 2 weeks after starting treatment. After 4 weeks of treatment, a wound was induced in the right hindlimb of rats and the wound size was measured every 3 days. At the end of the study, animals were sacrificed, blood, serum and hindlimb tissue were separated and used for further analyses. STZ treated rats showed a decrease in body weight, insulin, adiponectine level and soluble form of receptor of advanced glycation (sRAGE) expression and an increase in glucose, glycated haemoglobin A1c (HbA1c), tumor necrosis factor-α (TNF-α), advanced glycation end products level (AGEs) and receptor of advanced glycation end products (RAGE) expression compared to control group. This was associated with impaired performance in behavior tests and delayed wound healing. Treatment with telmisartan resulted in significant increase in body weight, serum adiponectin, serum sRAGE level and decreased TNF-α, insulin level, serum AGEs and RAGE compared to diabetes. Telmisartan lead to improvement only in gait base and intrastep distance in footprint parameters, while didn't improve hot plate latency or delayed wound healing. In conclusion, telmisartan may partially improve the deleterious effects of diabetes as peripheral neuropathy through its anti-glycation and anti-inflammatory effects