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Article 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, ZeynepObjectives: 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.Article Citation - WoS: 4Citation - Scopus: 4Effects 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, AbdullahBackground 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.Article Citation - WoS: 11Citation - Scopus: 13Protective 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, AbdullahAim: 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.Article Citation - WoS: 15Citation - Scopus: 15The 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, MustafaObjective: 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.Article Citation - WoS: 4Citation - Scopus: 4Effects 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, MustafaBackground 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.Article Citation - WoS: 11Citation - Scopus: 16Therapeutic 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 DoganIntroduction: 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.Article 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, MustafaAim: 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.Article Citation - WoS: 11Citation - Scopus: 14Protective 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, MustafaBackground 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.Article Bosentan Reduces Myocardial Ischemia-Reperfusion Injury in Rats(2025) Küçük, Ayşegül; Dursun, Alı Dogan; Arslan, Mustafa; Özer, Abdullah; Demirtas, Huseyin; Gulcan, Mehmet Burak; Yığman, ZeynepObjectives: This study aimed to investigate the cardioprotective effects of bosentan, an endothelin receptor antagonist, against myocardial ischemia-reperfusion injury (MIRI) in rats. Materials and Methods: Twenty-four adult Wistar-Albino rats were randomly divided into four groups: control, bosentan only, myocardial ischemia-reperfusion (MIR), and MIR-bosentan (MIR-B). Ischemia was induced by ligation of the left anterior descending coronary artery for 30 minutes, followed by 90 minutes of reperfusion. Bosentan was administered intraperitoneally at 30 mg/kg during ischemia in the MIR-B group. Histopathological evaluation assessed neutrophil infiltration, cardiomyocyte damage, tissue edema, and hemorrhage, while biochemical analyses measured total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and paraoxonase-1 (PON-1) activity in myocardial tissue. Results: The MIR group showed significantly increased histopathological injury scores, including neutrophil infiltration, cardiomyocyte damage, edema, and hemorrhage, compared to control and bosentan-only groups (p<0.001). Bosentan treatment significantly reduced these injury scores in the MIR-B group compared to the MIR group (p<0.05). Biochemically, the MIR group exhibited elevated TOS and OSI levels and reduced TAS and PON-1 activity, indicating oxidative stress. Bosentan administration significantly improved these parameters by lowering TOS and OSI levels, and by increasing TAS and PON-1 activity compared to the MIR group (p<0.05). Conclusion: In conclusion, bosentan demonstrated significant protective effects against MIRI by attenuating histological damage and oxidative stress in rat myocardium. These findings suggest that endothelin receptor antagonism with bosentan may offer a promising therapeutic approach to reduce myocardial injury following ischemia-reperfusion events such as those occurring during coronary artery bypass grafting. Further studies are needed to explore its clinical potential.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.
