Abstract Backround / Objectives: Alamandine (ALA), 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 quality of life, this study aims to investigate the protective effects of ALA against renal ischemia-reperfusion (I/R) injury in diabetic rats. Methods: Forty-eight 3-month-old male Sprague-Dawley rats were induced by administering a single intraperitoneal dose of 50 mcg/kg of streptozotocin (STZ). The rats were divided into four groups. Right nephrectomy was performed through dorso-lateral incisions in all rats, followed by the left renal vessels were occluded for 1 hour to induce ischemia. Reperfusion of the left kidney was initiated by removing the clamp, allowing 24 hours of reperfusion. Results: Histopathological examination of 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 of 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, while the ALA+I/R group exhibited preserved classical lobular structure with reduced histopathological changes. Conclusion: Our study demonstrates the protective effects of ALA on renal and liver tissues against damage induced by renal I/R injury in a diabetic background. Moreover, ALA exhibits protective effects against liver damage resulting from renal I/R injury.
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