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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 Effects of Pregabalin on Kidney Tissue in Spinal Cord Ischemia Reperfusion Injured Rats(Gazi Univ, Fac Med, 2021) Ceran, Emine Unal; Inan, Nurten; Kucuk, Aysegul; Ozer, Abdullah; Dursun, Ali Dogan; Tosun, Murat; Arslan, MustafaObjectives: The purpose of this study was to investigate the possible protective effects of low and high dose pregabalin that was administered in rat in a spinal cord ischemia-reperfusion (I/R) study model. Material and Method: We used 24 Wistar albino rats as subjects in our study. They were divided into 4 groups; randomized Control (C group), I/R (I/R group), I/R-low dose (30 mg/kg) pregabalin (I/R-LP group) and I/R-high dose (200 mg/kg) pregabalin (I/R-HP group). All groups have undergone a laparotomy intervention under anesthesia. In I/R group, a cross clamp was placed in the abdominal aorta just after the laparotomy for 120 minutes (to cause spinal cord ischemia injury) and then reperfusion was achieved by opening the vascular clamp. At the end of the study, kidney tissue was obtained for determining total oxidant status (TOS) and total antioxidant status (TAS) levels, histochemical and immunohistochemical determination. Results: Total Oxidative Status (TOS) enzyme activity was significantly higher in I/R group when compared to the control, I/R-LP and I/R-HP groups. Likewise, Total Antioxidant Status (TAS) enzyme activity was remarkably higher in I/R group when compared with the C, I/R-LP and I/R-HP groups. VEGF staining has yielded no expression in renal tissues. In microscopical analysis of the tissue slides which were immunohistochemically stained with p53 antibody, some crucial findings have been established as follows: As p53-expressing cells were not detected in the control group, the presence of p53-expressing cells were clearly identified at different intensities in several bowman capsules in the I/R group. However, no expression was detected in general tubules. Interestingly, p53 expression levels were prominently lower in low-dose pregabalin given group and considerably higher in the 200 mg/kg pregabalin administered group, which was more pronounced than the I/R group. Conclusion: Results established from the current study suggest that pregabalin given at different doses may have a partial protective effect in kidney tissues of rats undergone experimental spinal cord IR injury.

