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Background and Objectives : Lower-extremity ischemia-reperfusion injury can induce distant organ ischemia, and patients with diabetes are particularly susceptible to ischemia-reperfusion injury. Sevoflurane, a widely used halogenated inhalation anesthetic, and fullerenol C60, a potent antioxidant, were investigated for their effects on heart and lung tissues in lower-extremity ischemia-reperfusion injury in streptozotocin (STZ)-induced diabetic mice. Materials and Methods : A total of 41 mice were divided into six groups: control ( n = 6), diabetes-control ( n = 7), diabetes-ischemia ( n = 7), diabetes-ischemia-fullerenol C60 ( n = 7), diabetes-ischemia-sevoflurane ( n = 7), and diabetes-ischemia-fullerenol C60-sevoflurane ( n = 7). Diabetes was induced in mice using a single intraperitoneal dose of 55 mg/kg STZ in all groups except for the control group. Mice in the control and diabetes-control groups underwent midline laparotomy and were sacrificed after 120 min. The DIR group underwent 120 min of lower-extremity ischemia followed by 120 min of reperfusion. In the DIR-F group, mice received 100 μg/kg fullerenol C60 intraperitoneally 30 min before IR. In the DIR-S group, sevoflurane and oxygen were administered during the IR procedure. In the DIR-FS group, fullerenol C60 and sevoflurane were administered. Biochemical and histological evaluations were performed on collected heart and lung tissues. Results : Histological examination of heart tissues showed significantly higher necrosis, polymorphonuclear leukocyte infiltration, edema, and total damage scores in the DIR group compared to controls. These effects were attenuated in fullerenol-treated groups. Lung tissue examination revealed more alveolar wall edema, hemorrhage, vascular congestion, polymorphonuclear leukocyte infiltration, and higher total damage scores in the DIR group compared to controls, with reduced injury parameters in the fullerenol-treated groups. Biochemical analyses indicated significantly higher total oxidative stress, oxidative stress index, and paraoxonase-1 levels in the DIR group compared to the control and diabetic groups. These levels were lower in the fullerenol-treated groups. Conclusions : Distant organ damage in the lung and heart tissues due to lower-extremity ischemia-reperfusion injury can be significantly reduced by fullerenol C60.

Background: Ischemia-reperfusion injury (IRI) poses a significant challenge for physicians, necessitating the management of cell damage and the preservation of organ functions. Various surgical procedures, such as vascular surgery on extremities, temporary cross-clamping of the abdominal aorta in aortic surgery, and the use of a tourniquet in extremity surgeries, may induce lower limb IRI. The susceptibility to IRI is heightened in individuals with diabetes. This study aimed to investigate the effects of fullerenol C60 and sevoflurane on mouse muscle tissue in a lower limb IRI model and to assess their potential in preventing complications arising from ischemia-reperfusion in mice with streptozocin-induced diabetes., Methods: A total of 36 adult Swiss albino mice were randomly divided into six groups, each consisting of six mice: control group (group C), diabetes group (group D), diabetes-ischemia/reperfusion group (group DIR), diabetes-ischemia/reperfusion-fullerenol C60 group (group DIR-FC60), diabetes-ischemia/reperfusion-sevoflurane group (group DIR-S), and diabetes-ischemia/reperfusion-sevoflurane-fullerenol C60 group (DIR-S-FC60). Streptozocin (55 mg/kg) was intraperitoneally administered to induce diabetes in the relevant groups, with mice displaying blood glucose levels of 250 mg/dL or higher at 72 h were considered diabetic. After 4 weeks, all groups underwent laparotomy under anesthesia. In DIR-FC60 and DIR-S-FC60 groups, fullerenol C60 (100 mg/kg) was intraperitoneally administrated 30 min before the ischemia period. Sevoflurane, delivered in 100% oxygen at a rate of 2.3% and 4 L/min, was administered during the ischemia period in DIR-S and DIR-S-FC60 groups. In the IR groups, a microvascular clamp was placed on the infrarenal abdominal aorta for 120 min during the ischemia period, followed by the removal of the clamp and a 120-min reperfusion period. At the end of the reperfusion, gastrocnemius muscle tissues were removed for histopathological and biochemical parameter examinations., Results: Histopathological examination revealed a significant reduction in the disorganization and degeneration of muscle cells in the DIR-S-FC60 group compared to the DIR group (p = 0.041). Inflammatory cell infiltration was notably lower in the DIR-S, DIR-FC60, and DIR-S-FC60 groups than in the DIR group (p = 0.031, p = 0.011, and p = 0.013, respectively). The total damage scores in the DIR-FC60 and DIR-S-FC60 groups were significantly lower than in the DIR group (p = 0.018 and p = 0.008, respectively). Furthermore, the levels of malondialdehyde (MDA) in the DIR-S, DIR-FC60, and DIR-S-FC60 groups were significantly lower than in the DIR group (p < 0.001, p < 0.001, and p < 0.001, respectively). Catalase (CAT) enzyme activity in the DIR-S, DIR-FC60, and DIR-S-FC60 groups was higher than in the DIR group (p = 0.001, p = 0.014, and p < 0.001, respectively). Superoxide dismutase (SOD) enzyme activity in the DIR-FC60 and DIR-S-FC60 groups was also higher than in the DIR group (p < 0.001 and p = 0.001, respectively)., Conclusion: Our findings indicate that administering fullerenol C60 30 min prior to ischemia in diabetic mice, in combination with sevoflurane, led to a reduction in oxidative stress and the correction of IR-related damage in muscle tissue histopathology. We believe that the administration of fullerenol C60 before IR, coupled with sevoflurane administration during IR, exerts a protective effect in mice., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aimed to demonstrate whether fullerenol C60, sevoflurane anesthesia, or a combination of both had protective effects on the liver and kidneys in lower extremity ischemia-reperfusion injury (IRI) in mice with streptozocin-induced diabetes., Methods: A total of 46 Swiss albino mice were divided into six groups as follows: control group (group C, n=7), diabetes group (group D, n=7), diabetes-ischemia/reperfusion (group DIR, n=8), diabetes-ischemia/reperfusion-fullerenol C60 (group DIR-FC60, n=8), diabetes-ischemia/reperfusion-sevoflurane (group DIR-S, n=8), and the diabetes-ischemia/reperfusion-fullerenol C60-sevoflurane (group DIR-S-FC60, n=8). Fullerenol C60 (100mg/kg) was administered intraperitoneally 30 min before the ischemia-reperfusion procedure to the fullerenol groups (DIR-FC60 and DIR-S-FC60). In the DIR groups, 2 hours (h) ischemia-2h reperfusion periods were performed. In the sevoflurane groups, sevoflurane was applied during the ischemia-reperfusion period with 100% O 2 . Liver and kidney tissues were removed at the end of the reperfusion procedure for biochemical and histopathological examinations., Results: In liver tissue, hydropic degeneration, sinusoidal dilatation, pycnotic nuclei, prenecrotic cells, and mononuclear cell infiltration in parenchyma were significantly more frequent in group DIR than in groups D and group C. In terms of the histopathologic criteria examined, more positive results were seen in group DIR-FC60, and when group DIR-FC60 was compared with group DIR, the difference was significant. The best results in AST, ALT, glucose, TBARS levels, and SOD enzyme activities in liver tissue were in group DIR-FC60 compared with group DIR, followed by groups DIR-S-FC60 and DIR-S, respectively. Regarding TBARS levels and SOD enzyme activities in kidney tissue, the best results were in groups DIR-FC60, DIR-S-FC60, and DIR-S, respectively., Conclusion: According to our findings, it is clear that fullerenol C60 administered intraperitoneally 30 min before ischemia, alone or together with sevoflurane, reduces oxidative stress in distant organ damage caused by lower extremity IRI, and reduces liver and kidney tissue damage in histopathologic examinations., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Şengel et al.)

Aim: We want to investigate the protective effects of apelin-13 on myocardial ischemia reperfusion (I/R) injury., Material and Methods: 30 Wistar Albino rat were divided into 5 groups (n:6), namely control group (C), diabetes group (D), diabetes+apelin-13 group (DA), diabetes+I/R group (DIR) and diabetes I/R+apelin-13 group (DIR-A). Rats were subjected to 30‑min ischemia and 90‑min reperfusion. Biochemical and histopathological parameters were measured., Results: Caspase-3 enzyme activity was significantly higher in the DIR group than in the C, DA, and DIR-A groups. The intensity of caspase 3 enzyme activity was significantly higher in the I/R group than in all other groups. Inflammation and vascular dilatation were found significantly higher in the DIR group than in all other groups. Congestion was significantly higher in the DIR group than in the C and D groups. TOS enzyme activity was significantly higher in the DIR group than in the C, DA and DIR-A groups. TAS enzyme activity was significantly lower in the DIR group than in the C and DIR-A groups., Conclusion: We believe that the protective effects of apelin-13 in ischemia-reperfusion injury and its use indications can be demonstrated in detail as long as the findings we have reached in our study are supported by other studies (Tab. 2, Fig. 10, Ref. 43).

Objectives: Erythrocyte deformability and plasma viscosity are of crucial importance for the perfusion of tissues and organs. The aim of this study was to evaluate the effect of apelin-13 on erythrocyte deformability during IR heart injury in diabetic rats., Methods: Eighteen Wistar Albino rats were included in the study after streptozotocin (55 mg/kg) treatment for four weeks of observation for diabetes existence. The animals were randomly assigned to one of five experimental groups. In the Group C, DC (sham-control group) and DCA (sham-control group-apelin-13), the coronary artery was not occluded or re-perfused. In the Group DIR, a branch of the left coronary artery was occluded for 30 minutes followed by 90 minutes of re-perfusion to produce IR. In the Group DIRA, a branch of the left coronary artery was occluded for 30 minutes followed by 90 minutes of re-perfusion to produce IR, and apelin-13 was administrated via 10 µg.kg-1 IP route 30 minutes before ligating the left coronary artery.Deformability measurements were performed in erythrocyte suspensions containing Htc 5% in a PBS buffer., Results: The deformability index was significantly increased in diabetic rats; however, it was similar in Group DC, DCA and DIRA. It was significantly increased in the Group DIR when compared to the Group C, DIRA, DCA and DC. The relative resistance was increased in IR models., Conclusion: Erythrocyte deformability was decreased in rats having diabetes and IR injury. This injury might lead to further problems in microcirculation. It was shown that apeline-13 may be useful in enhancing the adverse effects of this type of injury (Fig. 1, Ref. 35).