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Article Citation - WoS: 7Ozone Administration Reduces Myocardial Ischemia Reperfusion Injury in Streptozotocin-Induced Diabetes Mellitus Rat Model(Baycinar Medical Publishing, 2024) Gulcan, M.B.; Demirtas, H.; Ozer, A.; Yıgman, Z.; Dursun, A.D.; Arslan, M.; Oktar, G.L.Objective: This study aimed to investigate the effects of ozone therapy on myocardial ischemia/reperfusion injury in a diabetic rat model. Methods: The experimental study included 38 male Wistar Albino rats weighing between 200 and 250 g. The rats were randomly assigned to five groups. The sham group included six rats, while the other groups had eight rats each. The other groups were the diabetic ozone group, the diabetic group, the diabetic ischemia/reperfusion group (DIR), and the diabetic ischemia/reperfusion ozone group (DIRO). A total of 32 rats received 65 mg/kg streptozotocin, and a week after the administration, diabetes was confirmed by measuring blood sugar. The rats were fed ad libitum for 40 days to reveal macrovascular complications of diabetes. Malondialdehyde, catalase, superoxide dismutase, paraoxonase-1, total oxidative status, total antioxidant status, and oxidative stress index were assessed. A TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay was employed to assess apoptosis. Results: Histologic and biochemical assessments showed the benefits of ozone in myocardial ischemia/reperfusion injury in diabetic rats. The DIRO group was found to be superior to the DIR group. Conclusion: Ozone has cardioprotective effects in streptozotocin-induced diabetic rats through its antioxidant properties against oxidative stress. The study is unique in terms of ozone’s protective effects in diabetic rats against myocardial ischemia/reperfusion injury. However, further studies are needed to confirm our findings. © (2024), (Baycinar Medical Publishing). All rights reserved.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 Citation - WoS: 4Citation - Scopus: 7Protective Effects of Bosentan Via Endothelin Receptor Antagonism in Experimental Ischemia-Reperfusion Injury in the Lower Limb of Rats(Dove Medical Press Ltd, 2025) Demirtas, Hueseyin; Oezer, Abdullah; Guelcan, Mehmet Burak; Yigman, Zeynep; Kuecuek, Ayseguel; Tekin, Esra; Arslan, MustafaObjective: This study aimed to evaluate the protective effects of bosentan, a dual endothelin receptor antagonist, against skeletal muscle ischemia-reperfusion injury (IRI) in rats. Methods: A total of 24 male Wistar Albino rats were divided into four groups: control (C, n=6), bosentan-treated (B, n=6), ischemiareperfusion (IR, n=6), and bosentan plus ischemia-reperfusion (B+IR, n=6). Bosentan (10 mg/kg) was administered 30 minutes prior to reperfusion. In the IR and B+IR groups, ischemia was induced using vascular bulldog clamps for 45 minutes, followed by 120 minutes of reperfusion. Results: Histological and biochemical assessments revealed significant differences among the groups. The disorganization and degeneration scores of the muscle cells in the B+IR group were significantly lower than those in the IR group (P = 0.001). The degree of interstitial edema in the IR group was markedly more severe than in the C and B groups (all P < 0.001), while the interstitial edema score in the B+IR group was significantly lower than that in the IR group (P < 0.001). The total muscle injury scores were markedly reduced in the B+IR group compared to the IR group (P < 0.001). Biochemically, TAS levels were significantly higher in the B+IR group compared to the IR group (1.03 f 0.18 vs 0.59 f 0.10 mmol/L, P = 0.016). Conversely, TOS (1.97 f 0.39 vs 2.86 f 0.43 IU/mg, P < 0.001) and OSI levels (P < 0.001) were significantly lower in the B+IR group. Additionally, paraoxonase (PON-1) enzyme activity was significantly reduced in the B+IR group compared to the IR group (P < 0.001). These findings suggest that bosentan exerts its protective effects by antagonizing endothelin-1 receptors, thereby mitigating vasoconstriction, oxidative stress, and inflammation. The observed reductions in muscle cell disorganization, interstitial edema, hemorrhage, neutrophil infiltration and oxidative stress markers underscore bosentan's potential as a therapeutic agent for managing ischemia-reperfusion injury. Conclusion: Bosentan demonstrates significant protective effects against skeletal muscle IRI by reducing oxidative stress and inflammation through endothelin receptor antagonism. These findings underscore bosentan's potential as a therapeutic agent for mitigating ischemia-reperfusion injury in vascular surgeries and managing critical limb ischemia in clinical settings. Further research is warranted to explore the long-term effects of bosentan on muscle recovery and systemic health following ischemia-reperfusion injury.Article Citation - WoS: 4Citation - Scopus: 5Antioxidant Activity of Micractinium Sp. (Chlorophyta) Extracts Against H2O2 Induced Oxidative Stress in Human Breast Adenocarcinoma Cells(Nature Portfolio, 2024) Bulut, Onur; Kose, Iskin Engin; Sonmez, Cagla; Oktem, Huseyin AvniIn response to the growing demand for high-value bioactive compounds, microalgae cultivation has gained a significant acceleration in recent years. Among these compounds, antioxidants have emerged as essential constituents in the food, pharmaceutical, and cosmetics industries. This study focuses on Micractinium sp. ME05, a green microalgal strain previously isolated from hot springs flora in our laboratory. Micractinium sp. cells were extracted using six different solvents, and their antioxidant capacity, as well as total phenolic, flavonoid, and carotenoid contents were evaluated. The methanolic extracts demonstrated the highest antioxidant capacity, measuring 7.72 and 93.80 mu mol trolox equivalents g-1 dry weight (DW) according to the DPPH and FRAP assays, respectively. To further characterize the biochemical profile, reverse phase high-performance chromatography (RP-HPLC) was employed to quantify twelve different phenolics, including rutin, gallic acid, benzoic acid, cinnamic acid, and beta-carotene, in the microalgal extracts. Notably, the acetone extracts of Micractinium sp. grown mixotrophically contained a high amount of gallic acid (469.21 +/- 159.74 mu g g-1 DW), while 4-hydroxy benzoic acid (403.93 +/- 20.98 mu g g-1 DW) was the main phenolic compound in the methanolic extracts under heterotrophic cultivation. Moreover, extracts from Micractinium sp. exhibited remarkable cytoprotective activity by effectively inhibiting hydrogen peroxide-induced oxidative stress and cell death in human breast adenocarcinoma (MCF-7) cells. In conclusion, with its diverse biochemical composition and adaptability to different growth regimens, Micractinium sp. emerges as a robust candidate for mass cultivation in nutraceutical and food applications.
