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  • Article
    Organ-Protective Effects of Fullerenol and Desflurane in a Rat Model of Ischemia–Reperfusion Injury
    (Nature Portfolio, 2025) Kip, Gulay; Koksal, Zeynep; Yigman, Zeynep; Kucuk, Aysegul; Arslan, Mustafa; Akarca Dizakar, Saadet Ozen; Sivgin, Volkan
    To investigate the protective effects of fullerenol applied before ischemia induction and desflurane anesthesia applied during ischemia-reperfusion (IR) induction in the lungs and kidneys of a lower-extremity IR injury rat model. After receiving ethical approval, we randomly divided 30 rats into five groups: sham (S), IR, IR with 100 mg/kg fullerenol (IR-FUL), IR with 6.7% desflurane (IR-DES), IR with 100 mg/kg fullerenol and 6.7% desflurane (IR-FUL-DES). Fullerenol was administered 30 min before the IR procedure in the IR-FUL and IR-FUL-DES groups, and desflurane was administered during the IR procedure in the IR-DES and IR-FUL-DES groups. During the procedure, an atraumatic microvascular clamp was placed in the aorta for 120 min. The clamp was then removed to achieve reperfusion for 120 min. Finally, at the end of reperfusion, we evaluated the extracted lung and kidney tissue samples and assessed them biochemically and histopathologically. The lung damage scores of the IR-FUL, IR-DES, and IR-FUL-DES groups were significantly lower than those of the IR group (p < .0001, p = .002, and p < .0001, respectively). The renal tubule injury scores of the IR, IR-FUL, IR-DES, and IR-FUL-DES groups were significantly higher than those of the S group (p < .0001). By contrast, the renal tubule injury scores of the IR-FUL and IR-FUL-DES groups were significantly lower than those of the IR group (p < .0001 and p = .001, respectively). Moreover, kidney intercellular adhesion molecule 1 (ICAM1) expression was significantly lower in all the treatment groups, particularly the IR-FUL group, than in the IR group, and lung ICAM1 expression was significantly lower in the IR-FUL and IR-FUL-DES groups than in the other treatment groups. In the lung and kidney tissues, thiobarbituric acid reactive substance levels, catalase activity, glutathione-S-transferase activity, and arylesterase activity were relatively high in the treatment groups. The application of fullerenol before and after desflurane anesthesia during IR has protective effects on rat lungs and kidneys. In particular, histopathology confirmed that the application of fullerenol 30 min before IR induction and desflurane anesthesia during IR induction reduced oxidative stress and alleviated IR-related damage in the lungs and kidneys. These findings may have important translational relevance, suggesting potential perioperative strategies for protecting organs from ischemia-reperfusion injury in clinical settings.
  • Article
    Citation - Scopus: 3
    Protective 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, Huseyin
    Aim: 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.