ABSTRACT Alamandine (ALA) is a heptapeptide discovered in 2013 within the renin‐angiotensin system (RAS). Given the high prevalence of diabetes mellitus (DM) in society and its comorbidities, especially renal failure, which significantly impairs the quality of life, this study aimed to investigate the protective effects of ALA against renal ischemia‐reperfusion (I/R) injury in diabetic rats. Our aim was to develop preventive therapies for DM and diabetic renal failure. Forty‐eight 3‐month‐old male Sprague‐Dawley rats were induced by administering a single intraperitoneal dose of 50 mg/kg of streptozotocin (STZ). Rats were divided into four groups. Right nephrectomy was performed through dorsolateral incisions in all rats, followed by occlusion of the left renal vessels for 1 h to induce ischemia. Reperfusion of the left kidney was initiated by removing the clamp and allowing 24 h of reperfusion. Histopathological examination of the kidney tissues revealed necrotic changes and tubular dilatation in the I/R group, which were significantly reduced in the ALA + I/R group. Immunohistochemical analysis showed increased immunoreactivity for interleukin‐6 (IL‐6) and caspase‐3 in the I/R group, whereas the ALA + I/R group demonstrated significantly lower immunoreactivity for these markers. Liver histology showed irregular hepatocyte cords and sinusoidal dilatation in the I/R group, whereas the ALA + I/R group exhibited a preserved classical lobular structure with reduced histopathological changes. Blood parameters, serum biochemistry, and tissue findings were also analyzed. Our study demonstrated the protective effects of ALA on renal and liver tissues against damage induced by renal I/R injury in a diabetic background. Moreover, ALA exhibited protective effects against liver damage resulting from renal I/R injury.
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