Browsing by Author "Arslan, Mustafa"

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Citation - WoS: 3
Citation - Scopus: 3
The Effect of Cerium Oxide (ceo₂) on Ischemia-Reperfusion Injury in Skeletal Muscle in Mice With Streptozocin-Induced Diabetes
(Mdpi, 2024) Ozer, Abdullah; Sengel, Necmiye; Kucuk, Ayseguel; Yigman, Zeynep; Ozdemir, Cagri; Kilic, Yigit; Arslan, Mustafa; Basic Sciences
Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, in temporary clamping of the aorta in aortic surgery, or following acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress such as DM. Cerium oxide (CeO2) nanoparticles mimic antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n = 6), diabetes group (group D, n = 8), diabetes-CeO2 (group DCO, n = 8), diabetes-ischemia/reperfusion (group DIR, n = 8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n = 8). The DCO and DIRCO groups were given doses of CeO2 of 0.5 mg/kg intraperitoneally 30 min before the IR procedure. A 120 min ischemia-120 min reperfusion period with 100% O-2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p = 0.047 and p = 0.022, respectively). In group DIRCO, total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p < 0.001). The oxidative stress index (OSI) was found to be significantly lower in group DIR compared with group DCO (p < 0.001). Paraoxanase (PON) enzyme activity was found to be significantly increased in group DIR compared with group DCO (p < 0.001). The disorganization and degeneration score for muscle cells, inflammatory cell infiltration score, and total injury score in group DIRCO were found to be significantly lower than in group DIR (p = 0.002, p = 0.034, and p = 0.001, respectively). Conclusions: Our results confirm that CeO2, with its antioxidative properties, reduces skeletal muscle damage in lower extremity IRI in diabetic mice.
The Effect of Cerium Oxide on Liver and Kidney in Lower Extremity Ischemia Reperfusion Injury in Streptozotocin -Induced Diabetic Mice
(Springernature, 2025) Erel, Selin; Ozdemir, Miray Gozde; Kucuk, Aysegul; Sarikaya, Badegul; Sezen, Saban Cem; Atli, Muharrem; Arslan, Mustafa; Basic Sciences
IntroductionIschemia-reperfusion injury (IRI) is a major concern in diabetic patients undergoing vascular procedures, causing significant damage to the liver and kidneys. The purpose of this study was to evaluate the protective effects of cerium oxide on the liver and kidneys of diabetic mice with lower extremity IRI.Materials and MethodsThirty Swiss albino mice were divided into five experimental groups: control (C), control diabetes (D), diabetes with cerium oxide (D-CEO2), diabetes with IRI (D-IRI), and diabetes with IRI treated with cerium oxide (D-IRI-CEO2). Diabetes was induced with streptozotocin (125 mg/kg) and lower-extremity IRI was induced by clamping the infrarenal aorta. Cerium oxide was administered intraperitoneally to the 0.5 mg/kg cerium oxide groups 30 min before ischemia. Liver and kidney tissue samples were subsequently analyzed through biochemical assays measuring the total antioxidant status, total oxidant status, oxidative stress index, and paraoxonase-1, as well as histopathological examinations.ResultsThe D-IRI group exhibited greater liver and kidney damage than the control group. The D-IRI-CeO2 group displayed reduced liver and kidney damage compared to the D-IRI group. In both the D-IRI and D-IRI-CeO2 groups, the total oxidant status, oxidative stress index, and paraoxonase-1 acitivity were higher, whereas the total antioxidant status levels were lower. In the D-IRI-CeO2 group, there was a decrease in total oxidant status, oxidative stress index, and paraoxonase-1, whereas total antioxidant status increased compared to D-IRI.ConclusionIntraperitoneal cerium oxide reduces oxidative stress and mitigates liver and kidney damage in diabetic mice subjected to lower extremity ischemia-reperfusion injury.
The Effect of Different Doses Apelin 13 on Erythrocyte Deformability in Rats
(Wiley, 2019) Dursun, Ali Dogan; Ozdemir, Cagri; Comu, Faruk Metin; Kucuk, Aysegul; Arslan, Mustafa; Basic Sciences
[No Abstract Available]
Citation - WoS: 9
Citation - Scopus: 9
The Effect of Sevoflurane and Fullerenol C 60 on the Liver and Kidney in Lower Extremity Ischemia-Reperfusion Injury in Mice With Streptozocin-Induced Diabetes
(Dove Medical Press Ltd, 2023) Sengel, Necmiye; Kucuk, Ayseguel; Ozdemir, Cagri; Sezen, Saban Cem; Kip, Gulay; Er, Fatma; Arslan, Mustafa
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% O2. 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.
Citation - WoS: 3
Citation - Scopus: 3
Effects of Cerium Oxide on Kidney and Liver Tissue Damage in an Experimental Myocardial Ischemia-Reperfusion Model of Distant Organ Damage
(Mdpi, 2024) Gunes, Isin; Dursun, Ali Dogan; Ozdemir, Cagri; Kucuk, Aysegul; Sezen, Saban Cem; Arslan, Mustafa; Ozer, Abdullah; Basic Sciences
Background and Objectives: Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO2) affects systemic anti-inflammatory response and inflammation. Therefore, in our study, we aimed to investigate whether CeO2 administration has a protective effect against myocardial I/R injury in the liver and kidneys. Materials and Methods: Twenty-four rats were randomly divided into four groups after obtaining approval from an ethics committee. A control (group C), cerium oxide (group CO), IR (group IR), and Cerium oxide-IR (CO-IR group) groups were formed. Intraperitoneal CeO2 was administered at a dose of 0.5 mg/kg 30 min before left thoracotomy and left main coronary (LAD) ligation, and myocardial muscle ischemia was induced for 30 min. After LAD ligation was removed, reperfusion was performed for 120 min. All rats were euthanized using ketamine, and blood was collected. Liver and kidney tissue samples were evaluated histopathologically. Serum AST (aspartate aminotransferase), ALT (alanine aminotransaminase), GGT (gamma-glutamyl transferase), glucose, TOS (Total Oxidant Status), and TAS (Total Antioxidant Status) levels were also measured. Results: Necrotic cell and mononuclear cell infiltration in the liver parenchyma of rats in the IR group was observed to be significantly increased compared to the other groups. Hepatocyte degeneration was greater in the IR group compared to groups C and CO. Vascular vacuolization and hypertrophy, tubular degeneration, and necrosis were increased in the kidney tissue of the IR group compared to the other groups. Tubular dilatation was significantly higher in the IR group than in the C and CO groups. TOS was significantly higher in all groups than in the IR group (p < 0.0001, p < 0.0001, and p = 0.006, respectively). However, TAS level was lower in the IR group than in the other groups (p = 0.002, p = 0.020, and p = 0.031, respectively). Renal and liver histopathological findings decreased significantly in the CO-IR group compared to the IR group. A decrease in the TOS level and an increase in the TAS level were found compared to the IR group. The AST, ALT, GGT, and Glucose levels are shown. Conclusions: CeO2 administered before ischemia-reperfusion reduced oxidative stress and ameliorated IR-induced damage in distant organs. We suggest that CeO2 exerts protective effects in the myocardial IR model.
Citation - WoS: 10
Citation - Scopus: 11
Effects of Dexmedetomidine Administered Through Different Routes on Kidney Tissue in Rats With Spinal Cord Ischaemia-Reperfusion Injury
(Dove Medical Press Ltd, 2022) Sengel, Necmiye; Koksal, Zeynep; Dursun, Ali Dogan; Kurtipek, Omer; Sezen, Saban Cem; Arslan, Mustafa; Kavutcu, Mustafa; Basic Sciences
Background: Ischaemia-reperfusion (IR) injury, which can be encountered during surgical procedures involving the abdominal aorta, is a complex process that affects distant organs, such as the heart, liver, kidney, and lungs, as well as the lower extremities. In this study, we aimed to contribute to the limited literature by investigating the protective effect of dexmedetomidine, which was administered through different routes, on kidney tissue in rats with spinal cord IR injury.Methods: A total of 30 rats were randomly divided into five groups: control (C group), IR (IR group), IR-intraperitoneal dexmedetomidine (IRIPD group), IR-intrathecal dexmedetomidine (IRITD group), and IR-intravenous dexmedetomidine (IRIVD group). The spinal cord IR model was established. Dexmedetomidine was administered at doses of 100 mu g/kg intraperitoneally, 3 mu g/ kg intrathecally, and 9 mu g/kg intravenously. Histopathologic parameters in kidney tissue samples taken at the end of the reperfusion period and biochemical parameters in serum were evaluated.Results: When examined histopathologically, tubular dilatation was found to be significantly reduced in the IRIVD, IRITD, and IRIPD groups compared with the IR group (p = 0.012, all). Vascular vacuolization and hypertrophy were significantly decreased in the IRIVD, IRITD, and IRIPD groups compared with the IR group (p = 0.006, all). Tubular cell degeneration and necrosis were significantly reduced in the IRIVD, IRITD, and IRIPD groups compared with the IR group (p = 0.008, p = 0.08, and p = 0.030, respectively). Lymphocyte infiltration was significantly decreased in the IRIVD and IRITD groups compared with the IR group (p = 0.006 and p = 0.06, respectively). Conclusion: It was observed that dexmedetomidine administered by different routes improved the damage caused by IR in kidney histopathology. We think that the renoprotective effects of dexmedetomidine administered intravenously and intrathecally before IR in rats are greater.
Effects of Pomegranate Seed Oil on Lower Extremity Ischemia-Reperfusion Damage: Insights into Oxidative Stress, Inflammation, and Cell Death
(MDPI, 2025) Bozok, Ummu Gulsen; Ergorun, Aydan Iremnur; Kucuk, Aysegul; Yigman, Zeynep; Dursun, Ali Dogan; Arslan, Mustafa; Basic Sciences
Aim: This study sought to clarify the therapeutic benefits and mechanisms of action of pomegranate seed oil (PSO) in instances of ischemia–reperfusion (IR) damage in the lower extremities. Materials and Methods: The sample size was determined, then 32 rats were randomly allocated to four groups: Control (C), ischemia–reperfusion (IR), low-dose PSO (IR + LD, 0.15 mL/kg), and high-dose PSO (IR + HD, 0.30 mL/kg). The ischemia model in the IR group was established by occluding the infrarenal aorta for 120 min. Prior to reperfusion, PSO was delivered to the IR + LD and IR + HD groups at doses of 0.15 mL/kg and 0.30 mL/kg, respectively, followed by a 120 min reperfusion period. Subsequently, blood and tissue specimens were obtained. Statistical investigation was executed utilizing Statistical Package for the Social Sciences version 20.0 (SPSS, IBM Corp., Armonk, NY, USA). Results: Biochemical tests revealed significant variations in total antioxidant level (TAS), total oxidant level (TOS), and the oxidative stress index (OSI) across the groups (p < 0.0001). The IR group had elevated TOS and OSI levels, whereas PSO therapy resulted in a reduction in these values (p < 0.05). As opposed to the IR group, TASs were higher in the PSO-treated groups. Histopathological analysis demonstrated muscle fiber degeneration, interstitial edema, and the infiltration of cells associated with inflammation in the IR group, with analogous results noted in the PSO treatment groups. Immunohistochemical analysis revealed that the expressions of Tumor Necrosis Factor-alpha (TNF-α), Nuclear Factor kappa B (NF-κB), cytochrome C (CYT C), and caspase 3 (CASP3) were elevated in the IR group, while PSO treatment diminished these markers and attenuated inflammation and apoptosis (p < 0.05). The findings demonstrate that PSO has a dose-dependent impact on IR injury. Discussion: This research indicates that PSO has significant protective benefits against IR injury in the lower extremities. PSO mitigated tissue damage and maintained mitochondrial integrity by addressing oxidative stress, inflammation, and apoptotic pathways. Particularly, high-dose PSO yielded more substantial enhancements in these processes and exhibited outcomes most comparable to the control group in biochemical, histological, and immunohistochemical investigations. These findings underscore the potential of PSO as an efficacious natural treatment agent for IR injury. Nevertheless, additional research is required to articulate this definitively.
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, Mustafa; Basic Sciences
Objectives: 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.
Citation - WoS: 1
Citation - Scopus: 1
Effects of Sevoflurane and Fullerenol C60 on the Heart and Lung in Lower-Extremity Ischemia-Reperfusion Injury in Streptozotocin-Induced Diabetes Mice
(Mdpi, 2024) Ornek, Ender; Alkan, Metin; Erel, Selin; Sarıkaya, Badegül; Dursun, Ali Dogan; Sarıkaya, Badegül; Arslan, Mustafa; Basic Sciences; Anesthesia Program
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 mu g/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.
Citation - WoS: 1
Evaluation of the Efficacy of Silymarin and Dexmedetomidine on Kidney and Lung Tissue in the Treatment of Sepsis in Rats With Cecal Perforation
(Spandidos Publ Ltd, 2024) Yavuz, Aydin; Kucuk, Aysegul; Ergorun, Aydan Iremnur; Dursun, Ali Dogan; Yigman, Zeynep; Alkan, Metin; Arslan, Mustafa; Basic Sciences
Sepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 mu g/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed.
Investigation of Analgesic Minimum Effective Dose of Apelin-13 With Different Doses of Intraperitoneal Injections and its Effects on Kidney Tissue
(Wiley, 2020) Dursun, Ali; Ozdemir, Cagri; Sezen, Saban; Kucuk, Aysegul; Arslan, Mustafa; Basic Sciences
[No Abstract Available]
Citation - WoS: 11
Citation - Scopus: 15
Irisin Protects Against Hind Limb Ischemia Reperfusion Injury
(Dove Medical Press Ltd, 2021) Kucuk, Aysegul; Polat, Yucel; Kilicarslan, Aydan; Sungu, Nuran; Kartal, Hakan; Dursun, Ali Dogan; Arslan, Mustafa; Basic Sciences
Aim: The aim of this study was to evaluate the effects of irisin in a murine model of hind limb ischemia reperfusion (I/R). Methods: The mice were divided into four groups (n = 6 in each group): control, irisin, ischemia reperfusion (I/R), and irisin-ischemia reperfusion (I-I/R). Irisin (0.5 mu g.g(-1), intraperitoneally [i.p.]) was administered 30 min before the I/R procedure. After 2 h of ischemia and 2.5 h of reperfusion, blood and tissue samples were taken for biochemical and histopathological analysis. The results were analyzed by Kruskal-Wallis and Mann-Whitney U-tests. Results: There was a statistically significant difference in the total antioxidant status (TAS) and total oxidant status (TOS) levels in all the groups. The TAS level in the I/R group was significantly lower than that in the control, irisin, and I-I/R groups, whereas the TOS level was significantly higher in the I/R group as compared with that in the other groups. Caspase3 activity and caspase-8 activity, indicators of inflammation, were significantly higher in the I/R and I-I/R groups as compared with those in the control and irisin groups. Conclusion: Irisin may have protective effects in skeletal muscle ischemia reperfusion injury.
Potential Protective Effects of Boldine in Rat With an Experimental Myocardial Ischemia-Reperfusion Model
(2025) Küçük, Ayşegül; Dursun, Alı Dogan; Arslan, Mustafa; Sezen, Şaban Cem; Yıldırım, Alperen Kutay; Özer, Abdullah; Yığman, Zeynep; Basic Sciences
Objectives: Myocardial ischemia-reperfusion injury (MIRI) remains a major challenge in cardiovascular medicine due to its complex pathophysiology involving oxidative stress, inflammation, and cellular dysfunction. Boldine, a potent natural alkaloid with antioxidant and anti-inflammatory properties, has demonstrated protective effects in various pathological conditions. However, its potential cardioprotective effects in MIRI remain largely unexplored. This study aims to evaluate the protective effects of Boldine in a rat model of MIRI by assessing oxidative stress markers, histopathological changes, and inflammatory responses. Materials and Methods: Male Albino Wistar rats were randomly assigned to four groups: Control, Boldine, myocardial ischemia-reperfusion (MIR), and myocardial ischemia-reperfusion + Boldine (MIR+B). Myocardial ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes, followed by 120 minutes of reperfusion. Boldine (50 mg/kg) was administered intraperitoneally at the onset of reperfusion. Cardiac tissue samples were collected for histopathological evaluation and biochemical analysis, including total antioxidant status (TAS), total oxidant status (TOS), and Oxidative Stress index (OSI). Results: Histopathological analysis revealed significant myocardial disorganization and inflammation in the MIR group compared to controls (p=0.05). Boldine treatment significantly reduced inflammation and myocardial disorganization in the MIR+B group (p<0.05), suggesting a protective effect. Biochemical analysis showed a marked decrease in TAS levels and an increase in TOS and OSI in the MIR group (p<0.001). However, Boldine administration significantly restored TAS levels and reduced TOS and OSI in the MIR+B group (p< 0.001), indicating attenuation of oxidative stress. Conclusion: Boldine exhibits significant cardioprotective effects in a rat model of MIRI by reducing oxidative stress, mitigating myocardial disorganization, and alleviating inflammation. These findings suggest that Boldine may serve as a therapeutic agent in ischemic heart disease. Further research is warranted to elucidate its precise mechanisms of action and potential clinical applications.
Citation - Scopus: 1
Protective 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, Mustafa; Basic Sciences
Objective: 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.
Citation - WoS: 2
Citation - Scopus: 4
Protective Effects of BPC 157 on Liver, Kidney, and Lung Distant Organ Damagein Rats with Experimental Lower-Extremity Ischemia–Reperfusion Injury
(MDPI, 2025) Demirtas, Hueseyin; Ozer, Abdullah; Yildirim, Alperen Kutay; Dursun, Ali Dogan; Sezen, Saban Cem; Arslan, Mustafa; Basic Sciences
Background and Objectives: Ischemia–reperfusion (I/R) injury can affect multiple distant organs following I/R in the lower extremities. BPC-157’s anti-inflammatory and free radical-neutralizing properties suggest its potential in mitigating ischemia–reperfusion damage. This study evaluates the protective effects of BPC-157 on remote organ damage, including the kidneys, liver, and lungs, in a rat model of skeletal muscle I/R injury. Materials and Methods: A total of 24 male Wistar albino rats were randomly divided into four groups: sham (S), BPC-157(B), lower extremity I/R(IR) and lower extremity I/R+BPC-157(I/RB). Some 45 min of ischemia of lower extremity was followed by 2 h of reperfusion of limbs. BPC-157 was applied to groups B and I/RB at the beginning of the procedure. After 2 h of reperfusion, liver, kidney and lung tissues were harvested for biochemical and histopathological analyses. Results: In the histopathological examination, vascular and glomerular vacuolization, tubular dilation, hyaline casts, and tubular cell shedding in renal tissue were significantly lower in the I/RB group compared to other groups. Lung tissue showed reduced interstitial edema, alveolar congestion, and total damage scores in the I/RB group. Similarly, in liver tissue, sinusoidal dilation, necrotic cells, and mononuclear cell infiltration were significantly lower in the I/RB group. Additionally, the evaluation of TAS, TOS, OSI, and PON-1 revealed a statistically significant increase in antioxidant activity in the liver, lung, and kidney tissues of the I/RB group. Conclusions: The findings of this study demonstrate that BPC-157 exerts a significant protective effect against distant organ damage in the liver, kidneys, and lungs following lower extremity ischemia–reperfusion injury in rats.
Citation - WoS: 7
Citation - Scopus: 9
Protective Effects of Hydrogen Rich Saline Solution in Rats With Experimental Myocardial Ischemia Reperfusion Injury
(Cell Press, 2023) Koksal, Zeynep; Kurtipek, Omer; Arslan, Mustafa; Dursun, Ali Dogan; Yigman, Zeynep; Ozer, Abdullah; Basic Sciences
Aim: The aim of our study is to show whether the administration of hydrogen-rich saline solution (HRSS) intraperitoneally before left main coronary artery (LAD) ischemia protects the myocardium against ischemia-reperfusion (IR) injury.Materials and methods: After ethics committee approval, 24 Wistar Albino rats were divided into 4 groups, 6 rats in each group. For experimental IR, myocardial ischemia was performed by LAD ligation. Left thoracotomy was performed without ischemia in the Control group (Group C). Left thoracotomy was performed without myocardial ischemia to the rats in the HRSS group, and HRSS was given intraperitoneally (ip) at a rate of 10 ml/kg throughout the procedure. In the MIRHRSS group, a single dose of 10 ml/kg HRSS was administered 5 min before reperfusion. Histopathological and biochemical parameters were compared in myocardial tissue samples taken at the end of the reperfusion period.Results: When the groups were compared among themselves in terms of TOS and TAS levels, there was a significant difference between the groups (p = 0.006, p = 0.002). The severity of cardiomyocyte degeneration was significantly greater in MIR group than that in the control and HRSS groups (p = 0.002 and p = 0.001, respectively), as well as severity score of cardiomyocyte degeneration was higher in MIR-HRSS group compared with HRSS group (p = 0.035).Conclusion: Our study shows that HRSS is protective in IR injury, with the application of HRSS 5 min before reperfusion, interstitial edema severity, subendocardial haemorrhage are reduced, and oxidant status parameters are increased, while antioxidant status parameters are decreased. We believe that when it is supported by other studies, the protective effects of HRSS on IR damage will be shown in detail and its indications will be expanded.
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.
Citation - WoS: 5
Citation - Scopus: 10
Therapeutic Efficacy of Boric Acid Treatment on Brain Tissue and Cognitive Functions in Rats With Experimental Alzheimer's Disease
(Dove Medical Press Ltd, 2023) Ozdemir, Cagri; Arslan, Mustafa; Kucuk, Aysegul; Yigman, Zeynep; Dursun, Ali Dogan; Basic Sciences
Introduction: Oxidative stress has an important role in the pathophysiology of Alzheimer's disease (AD), the most common type of dementia. Boric acid (BA) contributes significantly to the protection of the brain by reducing lipid peroxidation and supporting antioxidant defense. We aimed to evaluate the therapeutic potential of BA treatment in AD rats. Materials and Methods: Four groups were formed as Control (C), Alzheimer's (A), Alzheimer's + Boric acid (ABA), Boric acid (BA). Intracerebroventricular injection of Streptozotocin (STZ) was preferred to create an AD. After 4 weeks, BA was applied 3 times every other day. The Radial Arm Maze Test (RAMT) was used to evaluate memory and learning abilities. Biochemical and histopathological evaluations were made in the hippocampus. Results: Initial RAMT inlet/outlet (I/O) numbers were similar. Two weeks after STZ injection, I/O numbers decreased in group A and ABA compared to group C and BA (p<0.05). After the second BA application, I/O numbers increased in the ABA group compared to the A group (p<0.05). In group A, PON-1, TOS and OSI levels were higher and TAS levels were lower than in groups BA and C. After BA treatment, PON-1 and OSI levels were lower in the ABA group than in the A group (p<0.05). Although there was an increase in TAS value and a decrease in TOS, this did not make a statistical difference. The thickness of the pyramidal cell in CA1 and the granular cell layers in the dentate gyrus, and the number of intact and degenerated neurons in the pyramidal cell layer were similar between the groups. Discussion: Significant improvement in learning and memory abilities after BA application is promising for AD. Conclusion: These results show that BA application positively affects learning and memory abilities, and reduces oxidative stress. More extensive studies are required to evaluate histopathological efficacy.
Citation - Scopus: 1
Uav Detection and Ranging With 77-81 Ghz Fmcw Radar
(Ieee, 2022) Doganay, Bengisu; Arslan, Mustafa; Demir, Efe Can; Coruk, Remziye Busra; Gokdogan, Bengisu Yalcinkaya; Aydin, Elif; Department of Electrical & Electronics Engineering; Electrical-Electronics Engineering
In this study, detection of unmanned aerial vehicles (UAV), determination of radar cross-section (RCS) values, and range estimation were performed using a commercial off-the-shelf (COTS) millimeter-wave Frequency Modulated Continuous Wave (mmWave FMCW) radar system in the 77-81 GHz frequency band. The measurements were carried out in a laboratory environment using a single transceiver antenna without the need for an anechoic chamber. RCS values of different vertically and horizontally positioned UAVs were measured experimentally along the 360 degrees aspect angle, and the simulated results obtained from computational tool were compared with the experimental results. The measurement and simulation results, together with the range estimation, matched with high accuracy.