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Article Citation - WoS: 5Evaluation 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, MustafaSepsis 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.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, MustafaIntroduction 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: 1Citation - Scopus: 1Is 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 AydinOBJECTIVES: 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.skArticle Citation - WoS: 29Citation - Scopus: 32Effects of Exercise Training on Anxiety in Diabetic Rats(Elsevier, 2019) Caliskan, Hasan; Akat, Firat; Tatar, Yakup; Zaloglu, Nezahet; Dursun, Ali Dogan; Bastug, Metin; Ficicilar, HakanDiabetes 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.Article Citation - WoS: 5The Evaluation of Serum Endocan, Interleukin-6, and Crp Levels Following Sleeve Gastrectomy(Dove Medical Press Ltd, 2023) Sariyildiz, Gulcin Turkmen; Demir, Canan Cicek; Demir, Mehmet Emin; Arslan, Aykut Ilker; Banli, Oktay; Dursun, Ali DoganBackground: The excessive accumulation of fat tissue in obesity is the source of chronic low-level inflammation and causes future dysmetabolic and cardiovascular disorders. Removal of this excessive fat tissue with the aid of bariatric surgery (BS) techniques, such as sleeve gastrectomy, may reverse adverse inflammatory outcomes. The aim of this study is to investigate the impact of sleeve gastrectomy on inflammatory markers, specifically endocan, IL-6, and CRP, in individuals with obesity.Methods: Thirty-two patients with class 3 obesity and class 2 obesity + comorbidities were enrolled in the study. Clinical characteristics including age, comorbidity, body mass index (BMI), waist, and hip circumferences of the participants were noted before and 3 months after sleeve gastrectomy. Blood samples were collected during those periods to assess biochemical features such as serum endocan, interleukin-6 (IL-6), C-reactive peptide, fasting insulin, glycosylated hemoglobin A1c levels, and lipid panel. A statistical package program was used for the analysis of those parameters, and p<0.05 was accepted as significant at a 95.0% confidence interval.Results: BMI reduced from 43.55 +/- 6.78 to 36.16 +/- 6.14 kg/m(2) within 3 months following BS (p<0.001). Preoperative serum endocan, IL-6, and CRP levels were correlated with BMI, and in line with BMI reduction, their serum levels decreased after BS (p<0.05). HOMA-IR also reduced after BS, and both in the pre and post-BS periods correlated with BMI, IL-6, endocan, and CRP levels (p<0.05). The mean total body weight loss was 20.4% within 3 months post-BS.Conclusion: BS techniques are effective in weight loss and reversing the inflammatory processes caused by obesity. Serum endocan, IL-6, and CRP levels are promising markers for describing obesity-related inflammation and objectively checking the alleviation of inflammation following BS.Article Citation - WoS: 10Citation - 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 - Scopus: 2Effects of Eccentric Exercise on Different Slopes(Jmni, 2019) Gokce, Evrim; Akat, Firat; Dursun, Ali Dogan; Gunes, Emel; Bayram, Pinar; Billur, Deniz; Koc, Emine; Basic SciencesObjectives: Eccentric contraction occurs when the muscle lengthens under tension. Damage-induced responses seen in the muscle after eccentric exercise usually experienced by sedentary individuals. This study aims to investigate muscle damage on different slopes. Methods: 32 male Wistar albino rats randomly divided into four groups: sedentary, horizontal running, and eccentric exercise (-8 degrees, -16 degrees) groups. Animals ran for 90 min with the speed of 25 m/s for five days. After 48h from the last exercise, rats were sacrificed, and plasma creatine kinase (CK), heat shock protein 70 (HSP70) levels were examined. Plasma and soleus total oxidant/antioxidant status (TOS-TAS) and histological changes of soleus muscle assessed. Results: CK and HSP70 significantly increased in 16 degrees EE group. TOS increased at 16 degrees EE and 8 degrees EE, but oxidative stress index (OSI) was only high at 8 degrees EE group. Mononuclear cell infiltration and the angiogenesis increased in soleus after eccentric exercise, and there was a correlation with slope. Sarcomere breaks were detected in 16 degrees EE group also in a correlation with slope. Conclusions: Consequently, sedentary individuals are vulnerable to injuries induced by eccentric contraction. Therefore, our study provides information for reconsidering rehabilitation and training programs.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: 9Citation - Scopus: 15Therapeutic 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.
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