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Article Citation - Scopus: 3Protective Effects of Metformin in Non-Diabetic Rats With Experimentally Induced Lower Extremity Ischemia-Reperfusion Injury(Turkish National Vascular and Endovascular Surgery Society, 2025) Küçük, Ayşegül; Dursun, Alı Dogan; Arslan, Mustafa; Sezen, Şaban Cem; Yıldırım, Alperen Kutay; Özer, Abdullah; Demirtas, HuseyinAim: Lower extremity ischemia-reperfusion (IR) injury can lead to substantial skeletal muscle damage and systemic complications, primarily driven by oxidative stress and inflammation. In addition to its well-known glucose-lowering effects, metformin possesses antioxidant and anti-inflammatory properties that may confer protection against tissue damage caused by IR. This study aims to evaluate the potential protective effects of metformin on skeletal muscle injury using a rat model of lower extremity IR.Material and Methods: A total of twenty-four male Wistar albino rats were randomly divided into four experimental groups: Control (C), Ischemia-Reperfusion (IR), IR with metformin at 4 mg/kg (IR+M4), and IR with metformin at 8 mg/kg (IR+M8). Ischemia was induced by clamping the infrarenal aorta for 45 minutes, followed by a reperfusion period of 120 minutes. In the treatment groups, metformin was administered intraperitoneally at the onset of ischemia. Gastrocnemius muscle tissues were harvested for subsequent histopathological and biochemical evaluations, including measurements of Total Antioxidant Status (TAS), Total Oxidant Status (TOS), and Oxidative Stress Index (OSI).Results: Histopathological analysis demonstrated a significant reduction in muscle atrophy, degeneration, leukocyte infiltration, and fiber fragmentation in the IR+M8 group compared to the IR group. Biochemical assessments showed that TAS levels were considerably elevated, whereas TOS and OSI levels were markedly reduced in the metformin-treated groups, with the most prominent effects observed at the higher dosage of 8 mg/kg.Conclusion: The findings indicate that metformin exerts a dose-dependent protective effect against skeletal muscle injury resulting from lower extremity ischemia-reperfusion in rats. These protective properties are likely due to metformin’s antioxidant and anti-inflammatory mechanisms, highlighting its potential therapeutic value in mitigating IR-induced tissue damage.Article Bosentan Reduces Myocardial Ischemia-Reperfusion Injury in Rats(2025) Küçük, Ayşegül; Dursun, Alı Dogan; Arslan, Mustafa; Özer, Abdullah; Demirtas, Huseyin; Gulcan, Mehmet Burak; Yığman, ZeynepObjectives: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, against myocardial ischemia-reperfusion injury (MIRI) in rats. Materials and Methods: Twenty-four adult Wistar-Albino rats were randomly divided into four groups: control, bosentan only, myocardial ischemia-reperfusion (MIR), and MIR-bosentan (MIR-B). Ischemia was induced by ligation of the left anterior descending coronary artery for 30 minutes, followed by 90 minutes of reperfusion. Bosentan was administered intraperitoneally at 30 mg/kg during ischemia in the MIR-B group. Histopathological evaluation assessed neutrophil infiltration, cardiomyocyte damage, tissue edema, and hemorrhage, while biochemical analyses measured total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and paraoxonase-1 (PON-1) activity in myocardial tissue. Results: The MIR group showed significantly increased histopathological injury scores, including neutrophil infiltration, cardiomyocyte damage, edema, and hemorrhage, compared to control and bosentan-only groups (p<0.001). Bosentan treatment significantly reduced these injury scores in the MIR-B group compared to the MIR group (p<0.05). Biochemically, the MIR group exhibited elevated TOS and OSI levels and reduced TAS and PON-1 activity, indicating oxidative stress. Bosentan administration significantly improved these parameters by lowering TOS and OSI levels, and by increasing TAS and PON-1 activity compared to the MIR group (p<0.05). Conclusion: In conclusion, bosentan demonstrated significant protective effects against MIRI by attenuating histological damage and oxidative stress in rat myocardium. These findings suggest that endothelin receptor antagonism with bosentan may offer a promising therapeutic approach to reduce myocardial injury following ischemia-reperfusion events such as those occurring during coronary artery bypass grafting. Further studies are needed to explore its clinical potential.
