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  • Article
    Citation - WoS: 11
    Citation - Scopus: 16
    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
    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.
  • 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, Mustafa
    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.
  • Article
    Citation - WoS: 9
    Citation - Scopus: 13
    The Evaluation of Oxidative Stress in the Young Adults With Covid-19 Mrna Vaccines Induced Acute Pericarditis- Myopericarditis
    (Dove Medical Press Ltd, 2022) Dursun, Ali Dogan; Saricam, Ersin; Sariyildiz, Gulcin Turkmen; Iscanli, Murat Dogan; Cantekin, Omer Faruk
    Background: During COVID-19 pandemic, several vaccines have been developed such as mRNA vaccines. However, acute pericarditis and myocarditis/myopericarditis cases have been described after mRNA vaccination. The mechanism for the development of cardiac involvement is unknown. Potential mechanism for oxidative stress associated with vaccine-induced heart involvement is unidentified. This study aimed to examine the role of oxidative stress and the heart involvement in young adults vaccinated with COVID-19 mRNA vaccines. Methods: In this cross-sectional study, a total of 23 participants were included and 10 of these participants were asymptomatic patients (control group). Comparison of the cardiac involvement and control group was made by using troponin I, C-reactive protein (hsCRP), D-dimer levels, and oxidative stress tests including nitric oxide, and imaging techniques (ECG, echocardiography, cardiovascular magnetic resonance). Results: The median age of acute pericarditis group (10 patients) was 22 years (Q1-Q3: 18.5-31), and the mean age was 24.4 +/- 7.5 years. The median age of myopericarditis group (3 patients) was 22 years (Q1-Q3 18.0-25.0), and the mean age was 21.6 +/- 3.5 years. All the myopericarditis cases were male. The patients with myopericarditis had higher troponin I level, hsCRP, and D-dimer levels (troponin I level; 1600.00 ng/mL; D-dimer; 1.20 mu g/mL, hsCRP; 3.0 mg/L, respectively; p < 0.05). Serum nitric oxide levels and OSI (total oxidant status, H2O2/total antioxidant status) were lower in myopericarditis group than the control and acute pericarditis group (p < 0.05). This shows inflammatory and procoagulant state. Conclusion: Vaccine-induced myopericarditis cases are associated with oxidative stress test abnormality (abnormal NO, OSI levels). However, there is no relationship between NO levels and other oxidative stress tests difference in vaccine-induced acute pericarditis. It is thought that vaccine-induced pericarditis and myopericarditis could have different pathogenesis. This could make it necessary to reassess the second dose of vaccination for vaccine-induced cardiac involvement cases.
  • Article
    Citation - WoS: 11
    Citation - Scopus: 14
    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
    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.
  • Article
    Protective Role of Bromelain’s Antioxidant and Anti-Inflammatory Effects in Experimental Lower Limb Ischemia-Reperfusion Injury
    (Nature Portfolio, 2025) Sezen, Saban Cem; Demirtas, Huseyin; Yildirim, Alperen Kutay; Ozer, Abdullah; Dursun, Ali Dogan; Kucuk, Aysegul; Arslan, Mustafa; Ozalp, Veli Cengiz; Kucuk, Işın Gunes
    Ischemia-reperfusion (IR) injury is a multifaceted pathological process characterized by excessive oxidative stress and inflammatory responses upon restoration of blood flow. Bromelain, a proteolytic enzyme complex derived from pineapple, exhibits robust antioxidant and anti-inflammatory activities. This study aimed to evaluate the protective effects and underlying mechanisms of bromelain on oxidative stress and inflammation in an experimental rat model of lower limb ischemia-reperfusion injury. Twenty-four male Wistar Albino rats were randomly allocated into four groups: Sham-operated control (SHAM), Bromelain-only (BR), Ischemia-Reperfusion (IR), and Ischemia-Reperfusion with Bromelain treatment (IR + BR). Bromelain (40 mg/kg) was administered intraperitoneally before ischemia induction. The IR model involved 45 min of infrarenal abdominal aorta occlusion followed by 120 min of reperfusion. Oxidative biomarkers (total antioxidant status [TAS], total oxidant status [TOS], oxidative stress index [OSI]) and histopathological parameters (muscle atrophy, degeneration, leukocyte infiltration, internalization of nuclei, fragmentation, and hyalinization) were analyzed. Significant increases in muscle degeneration, leukocyte infiltration, nuclear internalization, fragmentation, and elevated oxidative stress biomarkers (increased TOS and OSI, decreased TAS) were observed in the IR group compared to controls. Bromelain treatment (IR + BR) significantly ameliorated these effects, reducing muscle tissue damage, inflammation, and oxidative imbalance compared to the untreated IR group. Bromelain effectively mitigates lower limb ischemia-reperfusion injury by reducing oxidative stress, restoring antioxidant capacity, and suppressing inflammatory responses. These protective effects suggest that bromelain holds potential as a therapeutic agent for managing oxidative and inflammatory damages associated with IR conditions, warranting further clinical investigation.
  • Article
    Citation - WoS: 4
    Citation - Scopus: 4
    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; Dagli, Asli; Yigman, Zeynep
    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.
  • Article
    Effectiveness of Boric Acid in Sepsis in Rats With Cecal Perforation
    (Springer Nature, 2025) Kurtipek, Ali Can; Dursun, Ali Dogan; Yigman, Zeynep; Ozdemir, Cagri; Kucuk, Aysegul; Gonullu, Ugur; Arslan, Mustafa
    Introduction and AimSepsis is a systemic inflammatory response that develops in the host against microorganisms, which results in end-organ damage. Boric acid (BA) has been shown to have immune modulatory effects in vitro and in animal studies. The aim of the study is to investigate the effects of high dose BA on lung and kidney tissues in rats with sepsis induced by the CLP method.Method28 rats were randomly divided into four groups: Group C (control group), Group BA, Group CLP (cecal ligation and puncture), and Group CLP + BA. Cecum was ligated below the ileocecal valve and punctured. BA was administered to the treatment groups at an intraperitoneal dose of 200 mg/kg, and at the end of 24 h, lung and kidney tissue samples were collected and evaluated for biochemical and histopathological parameters.ResultsHistopathologically, in kidney tissue, CLP + BA group showed significantly less peritubular capillary dilatation and brush border loss in the proximal tubule epithelium compared to the CLP group. In lung tissue, CLP + BA group had significantly less alveolar wall thickening compared to the CLP group. Biochemical analyses indicated that BA administration reduced oxidative stress in both renal and lung tissues.ConclusionWe found that intraperitoneal administration of high dose boric acid partially ameliorated the tissue damage in rats subjected to CLP induced sepsis. Further studies are needed regarding the dosage and application at different time points.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Is increased activator protein 1 in cerebrospinal fluid as a potential biomarker that distinguishes idiopathic intracranial from sclerosis?
    (Aepress Sro, 2024) Karabork, Seyda; Celik, Humeyra; Dursun, Ali Dogan; Ankarali, Handan; Turkoglu, Sule Aydin
    OBJECTIVES: To distinguish whether idiopathic intracranial hypertension (IIH) is a condition predisposing to multiple sclerosis (MS) or an isolated disease, the current gene transcription factor Activator Protein -1 (AP -1) was evaluated with its potential to differentiate both diseases. BACKGROUND: The aim of this study was to investigate the use of AP -1 as biomarkers for the discrimination of IIH and MS. METHODS: AP -1, TNF-alpha, and IL -6 protein values in the CSF of the cases were evaluated by the ELISA method. The numerical measures of the groups and the ability of AP -1 to distinguish the groups were analyzed with the ROC curve. RESULTS: There was no difference between the groups in CSF TNF-alpha, IL -6, CSF, and serum biochemistry analyses. However, it was determined that the AP -1 concentration (pg/ml) was significantly higher in the IIH group, the sensitivity of AP -1 in separating those with IIH was 75%, and the specificity in separating those with MS was 60% in those with an AP -1 concentration of 606.5 and above. CONCLUSION: According to our results, the fact that CSF TNF-alpha and IL -6 values did not differ in IIH compared to MS revealed that IIH could not methodologically control MS, and AP -1 was a supportive parameter in differentiating both diseases (Tab. 2, Fig. 1, Ref. 31) . Text in PDF www.elis.sk
  • Article
    Citation - WoS: 13
    Citation - Scopus: 16
    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
    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.
  • Article
    Citation - WoS: 29
    Citation - Scopus: 32
    Effects of Exercise Training on Anxiety in Diabetic Rats
    (Elsevier, 2019) Caliskan, Hasan; Akat, Firat; Tatar, Yakup; Zaloglu, Nezahet; Dursun, Ali Dogan; Bastug, Metin; Ficicilar, Hakan
    Diabetes mellitus (DM) is a common health problem, which manifests itself with chronic hyperglycemia and impaired insulin action. The prevalence of anxiety disorders tends to be high in the diabetic population. Exercise has a well-known anxiolytic effect, also demonstrated on rodents, but the effect of exercise on the DM-induced anxiety is still unknown. Female, Wistar albino rats were randomly divided into four groups (n=8) (C; EX; DM; DM+EX). DM was induced by injection (i.p.; 50 mg/kg) of Streptozotocin (STZ). Rats exercised in moderate intensity on the treadmill (15m/min; 5 degrees; 30 min) for 5 weeks. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT) and Elevated Plus Maze (EPM). According to OFT, central time and central entry have increased with in EX but not in DM+EX. There was no difference between C and DM. Central latency time didn't differ among groups. Unsupported rearing increased in both EX and DM+EX. There was no significant decrease in DM. Freezing time was significantly increased in the DM group. Exercise training reduced freezing time both in diabetic and non-diabetic animals. EPM results were similar. Time spent in open arm was increased significantly in exercise groups compared to their sedentary matches, and freezing time data were also parallel to OFT. Our study revealed that diabetes had shown an anxiogenic effect, which was not severe, and it only manifested itself on some behavioral parameters. Exercise training was reduced anxiety-like behavior both in diabetic and non-diabetic rats. However, because of the nature of exercise studies, it is hard to separate the anxiolytic effect of exercise from the alteration of locomotion.