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    Assessment of erythrocyte morphology in patients with type 2 diabetes mellitus: a pilot study of electron microscopy-based analysis in relation to healthy controls
    (Tubitak Scientific & Technological Research Council Turkey, 2021) Mortas, Tulay; Durmaz, Senay Arikan; Sezen, Saban Cem; Savranlar, Yasemin
    Background/aim: The present study aimed to assess erythrocyte morphology in newly diagnosed type 2 diabetes mellitus patients using scanning electron microscopy. Materials and methods: In total, 30 patients admitted to endocrine outpatient clinics were included in the study. The patients were divided into two groups according to their fasting blood glucose levels: type 2 diabetes mellitus (n = 15, fasting blood glucose levels >= 126 mg/dL) and control (n = 15, fasting blood glucose levels < 99 mg/dL). The patient's demographic characteristics, haemoglobin A1c levels, and scanning electron microscopy findings regarding erythrocyte morphology were recorded. Results: There was no significant difference between the control and type 2 diabetes mellitus group in terms of the participants' age (51.13 +/- 8.53 vs. 50.33 +/- 8.72 years, p = 0.8) and the male/female ratio (9/6 vs. 9/6). In the control group, discocytes were abundant, echinocytes were rare, and spherocytes were absent. On the other hand, discocytes were less common and echinocyte-shaped erythrocytes were more common in the type 2 diabetes mellitus group than in the control group. In addition, spherocytes were detected in the type 2 diabetes mellitus group. Moreover, the diameter of discocytes was significantly lower (p = 0.014), and blood glucose and haemoglobin A1c levels were significantly higher (p < 0.05 for both) in the type 2 diabetes mellitus group than in the control group. Conclusion: Our findings indicate that high glucose levels in type 2 diabetes mellitus patients lead to significant alterations in erythrocyte morphology, including decreased erythrocyte deformability and the formation of echinocytes and spherocytes due to eryptosis. The possibility of decreased erythrocyte deformability due to excessive eryptosis may disturb microcirculation in newly diagnosed, treatment-naive type 2 diabetes mellitus patients who do not have any complications.
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    Assessment of the Effects of Levosimendan and Nigella Sativa on Myocardial Ischemia Reperfusion Injury in Rats
    (Gazi Univ, Fac Med, 2018) Ozer, Abdullah; Kilic, Yigit; Sezen, Saban Cem; Kucuk, Aysegul; Mardin, Baris; Alkan, Metin; Oktar, Levent
    Objective: Ischemia-reperfusion injury is a chain of events put in place by tissue ischemia. Reperfusion following the damage of cell causes an active inflammatory response. In our research we tried to evaluate the protective effect of Levosimendan and Nigella Sativa on myocardial ischemia-reperfusion injury in rats. Methods: We included twenty-four Wistar albino rats in our research. The rats were randomly divided into four experimental groups. The coronary arteries of rats in Group C (control group) were not occluded or reperfused. Left anterior descending coronary artery was ligated for 30 min to perform myocardial IR and then reperfused for 2 h in the IR (IR), IR-Levosimendan (24 mu g/kg) (IRL) and IR-Nigella Sativa (0.2 mL/kg) (IRNS) group. Results: Inflammation findings were significantly higher in the IR group compared with the C, IR-NS, and IR-L groups (p=0.001, p=0.019, p=0.019, respectively). Compared with the C, IR-NS, and IR-L groups, the microscopic myocardial disorganization was significantly higher among the IR group (p<0.0001, p=0.007, p=0.001, respectively). The light microscopic myocardial tissue interstitial fibrosis levels were significantly higher in the IR group than in the C, IR-NS, and IR-L groups (p<0.0001, p=0.044, p=0.003, respectively). Conclusion: Levosimendan and NS administration at the beginning of myocardial ischemia can provide varying degrees of protection against negative effects of variations in light microscopic inflammation findings, myocardial disorganization degrees and myocardial tissue interstitial fibrosis levels.
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    Assessment of the effects of levosimendan and thymoquinone on lung injury after myocardial ischemia reperfusion in rats
    (Dove Medical Press Ltd, 2018) Sezen, Saban Cem; Kucuk, Aysegul; Ozer, Abdullah; Kilic, Yigit; Mardin, Baris; Alkan, Metin; Tosun, Murat
    Aim: The aim of this study was to investigate the effects of levosimendan and thymoquinone (TQ) on lung injury after myocardial ischemia/reperfusion (I/R). Materials and methods: Twenty-four Wistar albino rats were included in the study. The animals were randomly assigned to 1 of 4 experimental groups. In Group C (control group), left anterior descending artery was not occluded or reperfused. Myocardial I/R was induced by ligation of the left anterior descending artery for 30 min, followed by 2 h of reperfusion in the I/R, I/R-levosimendan (24 mu g/kg) (IRL) group, and I/R-thymoquinone (0.2 mL/kg) (IRTQ) group. Tissue samples taken from the lungs of rats were histochemically stained with H&E and immunohistochemically stained with p53, Bcl 2, Bax, and caspase 3 primer antibodies. Results: Increased expression of p53 and Bax was observed (4+), especially in the I/R group. In IRTQ and IRL groups, expression was also observed at various locations (2+, 3+). H&E staining revealed that that the lungs were severely damaged and the walls of the alveoli were too thick, the number of areas examined was increased during the evaluation. Caspase 3 expression was observed to be at an (1+, 2+) intensity that was usually weak and diffuse in multiple areas. Bcl 2 was not found to be expressed in any of the tissues. H&E staining revealed that that the lungs were severely damaged in the I/R group, with the walls of the channels and alveoli thickened and edematous, and also an intense inflammatory cell migration was observed. Immunohistochemical staining was more prominent in inflammatory areas and structures around the terminal bronchioles. Conclusion: The findings in our study have shown that administration of levosimendan and TQ during I/R increases expression of caspase 3, p53, and Bax in lung tissue and has a protective effect on lung as distant organ. We suggest that findings of this study be elucidated with further large-scale clinical studies.
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    Dexmedetomidine's Effects on the Livers and Kidneys of Rats with Pancreatic Ischemia-Reperfusion Injury
    (Dove Medical Press Ltd, 2024) Bostanci, Hasan; Erel, Selin; Kucuk, Ayseguel; Kip, Guelay; Sezen, Saban Cem; Gokgoz, Seda; Atli, Muharrem
    Objective: Pancreatic surgeries inherently cause ischemia-reperfusion (IR) injury, affecting not only the pancreas but also distant organs. This study was conducted to explore the potential use of dexmedetomidine, a sedative with antiapoptotic, anti-inflammatory, and antioxidant properties, in mitigating the impacts of pancreatic IR on kidney and liver tissues. Methods: A total of 24 rats were randomly divided into four groups: control (C), dexmedetomidine (D), ischemia reperfusion (IR), and dexmedetomidine ischemia reperfusion (D-IR). Pancreatic ischemia was induced in the IR and D-IR groups. Dexmedetomidine was administered intraperitoneally to the D and D-IR groups. Liver and kidney tissue samples were subjected to microscopic examinations after hematoxylin and eosin staining. The levels of thiobarbituric acid reactive substances (TBARS), aryllesterase (AES), catalase (CAT), and glutathione S-transferase (GST) enzyme activity were assessed in liver and kidney tissues. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine were measured. Results: A comparison of the groups revealed that the IR group exhibited significantly elevated TBARS (p < 0.0001), AES (p = 0.004), and CAT enzyme activity (p < 0.0001) levels in the liver and kidney compared to groups C and D. Group D-IR demonstrated notably reduced histopathological damage (p < 0.05) and low TBARS (p < 0.0001), AES (p = 0.004), and CAT enzyme activity (p < 0.0001) in the liver and kidney as well as low AST and ALT activity levels (p < 0.0001) in the serum compared to the IR group. Conclusion: The preemptive administration of dexmedetomidine before pancreatic IR provides significant protection to kidney and liver tissues, as evidenced by the histopathological and biochemical parameters in this study. The findings underscored the potential therapeutic role of dexmedetomidine in mitigating the multiorgan damage associated with pancreatic surgeries.
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    Effect of Cerium Oxide on Kidney and Lung Tissue in Rats with Testicular Torsion/Detorsion
    (Hindawi Ltd, 2022) Ozdemirkan, Aycan; Kurtipek, Ali Can; Kucuk, Aysegul; Ozdemir, Cagri; Yesil, Suleyman; Sezen, Saban Cem; Kavutcu, Mustafa
    Introduction. Testicular torsion is a surgical emergency that results in testicular ischemia as a result of rotation of the spermatic cord around itself. Oxidative damage occurs in the testis and distant organs with the overproduction of free radicals and overexpression of proinflammatory cytokines by reperfusion after surgery. In this study, we aimed to investigate the effects of cerium oxide (CeO2), an antioxidant nanoparticle, on lung and kidney tissues in testicular torsion/detorsion (T/D) in rats. Materials and Methods. After ethics committee approval, 24 rats were equally (randomly) divided into 4 groups. Left inguinoscrotal incision was performed in the control (C) group. In group CeO2, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before inguinoscrotal incision. In group T/D, unilateral testicular T/D was achieved by performing an inguinoscrotal incision and rotating the left testis 720 degrees clockwise, remaining ischemic for 120 minutes, followed by 120 minutes of reperfusion. In group CeO2-T/D, 0.5 mg/kg CeO2 was given intraperitoneally 30 minutes before testicular T/D. At the end of the experiment, lung and kidney tissues were removed for histopathological and biochemical examinations. Results. Glomerular vacuolization (GV), tubular dilatation (TD), tubular cell degeneration and necrosis (TCDN), leukocyte infiltration (LI), and tubular cell spillage (TCS) in renal tissue were significantly different between groups (p = 0.012, p = 0.049, p < 0.003, p = 0.046, and p = 0.049, respectively). GV and TCDN were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.042 and p = 0.029, respectively). Lung tissue neutrophil infiltration, alveolar thickening, and total lung injury score (TLIS) were significantly different between groups (p = 0.006, p = 0.001, and p = 0.002, respectively). Neutrophil infiltration and TLIS were significantly decreased in group CeO2-T/D compared to group T/D (p = 0.013 and p = 0.033, respectively). Lung and kidney tissue oxidative stress parameters were significantly different between groups (p < 0.05). Renal tissue glutathione-stransferase (GST), catalase (CAT), and paraoxonase (PON) activities were significantly higher, and malondialdehyde (MDA) levels were significantly lower in group CeO2-T/D than in group T/D (p = 0.049, p = 0.012, p < 0.001, and p = 0.004, respectively). GST and PON activities were higher, and MDA levels were lower in group CeO2-T/D than in group T/D in the lung tissue (p = 0.002, p < 0.001, and p = 0.008, respectively). Discussion. In our study, cerium oxide was shown to reduce histopathological and oxidative damage in the lung and kidney tissue in a rat testis torsion/detorsion model.
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    Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats
    (Anaesthesia Pain & Intensive Care, 2016) Sezen, Saban Cem; Isik, Berrin; Bilge, Mustafa; Arslan, Mustafa; Comu, Faruk Metin; Ozturk, Levent; Kavutcu, Mustafa
    Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus. Methodology: Twenty-eight Wistar Albino rats were randomised into four groups as control (C), diabetic (DC), diabetic with hepatic ischemia-reperfusion injury (DIR), and diabetic but administered dexmedetomidine followed by hepatic IRI (DIRD) groups. Hepatic tissue samples were evaluated histopathologically by semiquantitative methods. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathion s-transpherase (GST), and catalase (CAT) enzyme levels were investigated in liver and kidney tissues as oxidative state parameters. Results: In Group DIR; hepatocyte degeneration, sinusoidal dilatation, pycnotic nucleus, and necrotic cells were found to be more in rat hepatic tissue; while mononuclear cell infiltration was higher in the parenchyme. MDA levels were significantly lower; but SOD levels were significantly higher in Group DIRD with regard to Group DIR. In the IRI induced diabetic rats' hepatic and nephrotic tissues MDA levels, showing oxidative injury, were found to be lower. SOD levels, showing early antioxidant activity, were higher. Conclusion: The enzymatic findings of our study together with the hepatic histopathology indicate that dexmedetomidine has a potential role to decrease IRI.
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    Effect of Dexmedetomidine on Lung Tissue Lower Extremity Ischemia Reperfusion Injury in Streptozotocin Induced Diabetic Rats
    (GAZI UNIV, FAC MED, 2020) Sezen, Saban Cem; Celik, Ilknur Aytekin; Aydin, Muhammed Enes; Ozterlemez, Naciye Turk; Arslan, Mustafa; Erbatur, Meral Erdal; Kavutcu, Mustafa
    Objective: The aim of our study was to investigate the effects of dexmedetomidine on lung tissue in rat's lower extremity after undergoing an ischemia reperfusion (I/R) injury. Material and methods: After obtaining ethical committee approval, 24 Wistar albino rats (200-270 gr) were randomly divided into four groups: (Control (Group C), diabetes-control (Group DC), diabetes I/R (Group DIR), and diabetes-I/R-dexmedetomidine (Group DIRD). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DC. In Group DIR, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DIRD, 100 mu g/kg of dexmedetomidine were administered intraperitoneally. Results: When the groups' lung tissue neutrophil infiltration/aggregation light microscopic findings were compared to each other, a significant difference was observed among the groups (p=0.003). When the groups' lung tissue injury score light microscopic findings were compared, a significant difference was observed among the groups (p=0.001). When groups were compared to each other in terms of lung tissue MDA levels and SOD activities, a significant difference was observed (p=0.002, p=0.018, respectively). Conclusion Our results confirm that dexmedetomidine has protective effects against the lung damage resulting from IR in diabetic rats. However, future studies should be conducted to evaluate these effects.
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    Effects of Amantadine on Liver and Lung Tissue in Hepatic Ischemia Reperfusion Injury in Rats
    (Gazi Univ, Fac Med, 2023) Sahin, Fatih; Tuna, Ayca Tas; Unal, Yusuf; Arslan, Mustafa; Yazar, Hayrullah; Sezen, Saban Cem; Gozukara, Sezen Irmak
    Background: N-Methyl D-Aspartate (NMDA) receptor blockers have been shown to have protective effects against ischemia/reperfusion (I/R) injury in various tissues. The aim of this study was to investigate the effects of amantadine on liver and lung tissue in hepatic I/R injury. Materials and Methods: Twenty-four rats divided into 4 groups: the Sham Group (S), the Amantadine Group (A), the I/R Group (I/R) and the I/R + Amantadine Group (I/R-A). In Group A and Group I/R-A, 45 mg/kg of amantadine was administered before surgery. In Group I/R and Group I/R-A, an atraumatic vascular clamp was applied to the structures in the left portal triad for 45 minutes and reperfusion period was 2 hours after declampage. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) enzyme levels were were studied in liver and lung tissues. Additionally tissues were examined histopathologically. Results: No significant difference was observed in tissue MDA, SOD, and CAT levels among four groups (p >0.05). Polymorphonuclear cell infiltration and the scores of hepatocyte degeneration, sinusoidal dilatation, pycnotic core, and necrosis cell were significantly higher in Group I/R than other groups (p<0.05). Regarding to the lung tissue, the neutrophil/lymphocyte infiltration score was significantly lower in Group S and A than in Group I/R (respectively; p= 0.007, 0.011), and it was significantly higher in Group I/R-A than in Group S (p = 0.014). The alveolar wall thickening score was significantly higher in Group I/R than the other groups (p <0.0001). Conclusion: Amantadine may have a protective effect against I/R damage, as it reduces histopathological changes caused by I/R damage.
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    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
    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.
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    Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion injury in streptozotocin induced diabetic rats
    (Taylor & Francis Ltd, 2017) Erbatur, Meral Erdal; Sezen, Saban Cem; Bayraktar, Aslihan Cavunt; Arslan, Mustafa; Kavutcu, Mustafa; Aydin, Muhammed Enes
    Aim: The aim of this study was to investigate whether dexmedetomidine - administered before ischemia - has protective effects against lower extremity ischemia reperfusion injury that induced by clamping and subsequent declamping of infra-renal abdominal aorta in streptozotocin-induced diabetic rats. Material and Methods: After obtaining ethical committee approval, four study groups each containing six rats were created (Control (Group C), diabetes-control (Group DM-C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R-D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DMC. In Group DM-I/R, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100 mu g/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia period. At the end of reperfusion, period biochemical and histopathological evaluation of renal tissue specimen were performed. Results: Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD), Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST) levels were found significantly higher in Group DM-I/R when compared with Group C and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST levels were significantly lower than those measured in the Group D-I/R. In histopathological evaluation, glomerular vacuolization (GV), tubular dilatation (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and tubular cell spillage (TCS) in Group DM-I/R were significantly increased when compared with the control group. Also, GV, VVH, and THC levels in the dexmedetomidine-treated group (Group DM-I/R-D) were found significantly decreased when compared with the Group DM-I/R. Conclusion: We found that dexmedetomidine - 100 mu g/kg intraperitoneally - administered 30 minutes before ischemia in diabetic rats ameliorates lipid peroxidation, oxidative stress, and I-R-related renal injury. We suggest that dexmedetomidine administration in diabetic rats before I/R has renoprotective effects.
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    Effects of esmolol on lung injury induced by lower extremity Ischemia-reperfusion
    (Bayrakol Medical Publisher, 2022) Sabuncu, Ulku; Sezen, Saban Cem; Kucuk, Aysegul; Salman, Nevriye; Sabuncu, Timucin; Kip, Gulay; Kurtipek, Omer
    Aim: After hind limb ischemia-reperfusion (I/R), impairments in remote organs are frequent. Lung tissue is the organ most affected by the remote organ damage. The lung damage increases ventilatory support, the need for inotropic agents and mortality. Many drugs and methods have been used in attempts to prevent or reduce this damage. The aim of this study is to investigate the protective effects of esmolol infusion on lung tissue prior to I/R created in the lower extremity. Material and Methods: The study was performed between 11 and 14 April 2018 in Gazi University Experimental Animal Research Center, Ankara, Turkey. After obtaining ethics committee approval, 24 rats were randomly divided into 4 groups: Control (Group C), Esmolol (Group E), Ischemia-reperfusion (Group I/R), and I/R-Esmolol (Group I/RE). Esmolol (200 mu g/kg/min intravenous) was applied 30 minutes before the procedure. The biochemical and histopathological parameters of lung tissue samples were compared. Results: Neutrophil infiltration/aggregation, alveolar wall thickness, and total lung injury scores were significantly higher in the I/R group than in the C and E groups. In addition, neutrophil infiltration/aggregation, alveolar wall thickness, and total lung injury scores in the I/R group were statistically higher than in the I/R-E group (p=0.030, p=0.010, p=0.001, respectively). Malondialdehyde levels, catalase (CAT) and paraoxonase (PON) enzyme activities in the I/R group were significantly higher than in the C, E, and I/R-E groups. Glutathione S- transferase ( GSH) enzyme activity was similar in all groups. Discussion: It was found that esmolol infusion at 200 mu g/kg/min intravenously-reduced oxidative stress when administered 30 minutes before ischemia in rats and partially corrected the damage caused by I/R in lung histopathology.
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    The Effects of High Dose Sugammadex on Rat Kidney Tissue Following Unilateral Ureteral Obstruction
    (Gazi Univ, Fac Med, 2018) Dogrul, Fikriye; Bozkirli, Fusun; Sezen, Saban Cem; Arpaci, Hande; Boyunaga, Hakan; Arslan, Mustafa; Unal, Yusuf
    Background: Unilateral ureteral obstruction (UUO) is commonly used model showed to imitate process of obstructive nephropathy in a feasible. The aim of this study is to evaluate the histopathological and biochemical effects of high doses sugammadex on kidney tissue of the rats those have early and late phase renal failure induced by UUO. Materials and Methods: Thirty male Wistar albino rats were randomly divided into five study groups. Control Group(C), UUO for 1 week Group(UUO-1), UUO-1 week treated with rocuronium and 96mg.kg(-1) Sugammadex Group(UUO-1 week-96S), UUO for 3 weeks Group(UUO-3) and UUO-3 weeks treated with rocuronium and 96mg.kg(-1 )Sugammadex Group(UUO-3 week-96S). The blood samples are stored at -20 degrees and MDA and NO were studied in the serum. Kidney tissue was removed for histopathological examination. Results: In the histopathological examination of all parameters (glomerular vacuolization(GV), tubular dilatation(TD), Vascular vacuolisation and hypertrophy(VVH), tubular cell degeneration and necrosis(TCDN), Bowman's space dilatation(BSD), tubular hyaline cylinders(THC), lymphocyte infiltration(LI), tubular cell sloughing(TCS), significant difference was observed for the kidney at the obstruction side. After 3 weeks, in the side of the all unobstructed groups' kidney tissues, significantly higher GV scores were detected compared with the GroupC. TD was observed more for the UUO1, UUO3 and UUO3S groups when compared with GroupC. And TCDN was observed more for the UUO1S and UUO3S groups when compared with GroupC. When the groups were compared with each other; it is observed that MDA and NO enzyme activities of UUO1S, UUO3 and UUO3S groups were significantly difference GroupC. Conclusion: High dose of sugammadex (96 mg.kg(-1)) can be used safely in UUO cases, on the other hand significant attention should be paid in bilateral ureteral obstruction cases. Our findings may be a guide for future animal and human studies investigating the effects of sugammadex on kidney tissue.
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    Evaluation of the Effect of Different Inhalation Agents on Ovaries with Hyperthermic Intraperitoneal Chemotherapy: An Experimental Study
    (Mdpi, 2024) Sen, Ozlem; Aslan, Esra; Kalayci, Dilek; Kucuk, Aysegul; Baskan, Semih; Sezen, Saban Cem; Arslan, Mustafa
    Background and Objectives: Cisplatin is a chemotherapeutic drug that is frequently used with hyperthermic intraperitoneal chemotherapy (HIPEC). Cisplatin-induced gonadotoxicity leads to a depletion of the ovarian reserve, causing premature ovarian insufficiency. This study aimed to investigate the impact of hyperthermia on cisplatin-induced ovarian toxicity and to determine whether sevoflurane or desflurane could be a more appropriate choice of anesthetic for reducing ovarian toxicity in HIPEC procedures. Materials and Methods: A total of 24 New Zealand rabbits were randomly divided into 4 groups as follows: Group H: HIPEC (cisplatin 7 mg/kg), Group HS: HIPEC (cisplatin 7 mg/kg) + 3% sevoflurane (2 h), Group HD: HIPEC (cisplatin 7 mg/kg) + 6% desflurane (2 h), and Group C: Control (Saline). Two catheters were placed in the abdominal cavity, the upper and lower quadrants. The perfusate was heated to 42 degrees C and given intraperitoneally for 90 min at a rate of 4 mL/min by catheters. Ovarian tissues were collected for Hematoxylin and Eosin staining and immunohistochemical analysis. Results: The primary follicle number was significantly decreased in Group H and HD compared to the C group (p < 0.05). Bax expression was high in Group H, according to all groups (p < 0.0001). Bax expression significantly decreased after sevoflurane, compared to group H (p = 0.012). The bcl-2 expression decreased in all groups compared to the C group. Bcl-2 expression was increased with sevoflurane compared to the H group (p = 0.001). Caspase 3 and p53 expression increased in all groups compared to the C group. p53 expression was decreased with sevoflurane and desflurane compared to the H group (p = 0.002, p = 0.008, respectively). Conclusions: The application of cisplatin with the intraoperative HIPEC method caused ovarian damage. According to our results, sevoflurane anesthesia could be a better option in mitigating cell death I the n ovarian reserve (follicle count) and apoptosis in the HIPEC procedures. We think that our findings should be supported by large series of clinical and experimental studies.
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    Evaluation of the effect of enriched hydrogen saline solution on distant organ (lung) damage in skeletal muscle ischemia reperfusion in rats
    (Sage Publications Ltd, 2024) Ozer, Abdullah; Erel, Selin; Kucuk, Aysegul; Demirtas, Hueseyin; Sezen, Saban Cem; Boyunaga, Hakan; Oktar, Gursel Levent
    Introduction Ischemia-reperfusion (IR) injury is a major concern that frequently occurs during vascular surgeries. Hydrogen-rich saline (HRS) solution exhibits antioxidant and anti-inflammatory properties. This study aimed to examine the effects of HRS applied before ischemia in the lungs of rats using a lower extremity IR model. Material and Methods: After approval was obtained from the ethics committee, 18 male Wistar albino rats weighing 250-280 g were randomly divided into three groups: control (C), IR and IR-HRS. In the IR and IR-HRS groups, an atraumatic microvascular clamp was used to clamp the infrarenal abdominal aorta, and skeletal muscle ischemia was induced. After 120 min, the clamp was removed, and reperfusion was achieved for 120 min. In the IR-HRS group, HRS was administered intraperitoneally 30 min before the procedure. Lung tissue samples were examined under a light microscope and stained with hematoxylin-eosin (H&E). Malondialdehyde (MDA) levels, total sulfhydryl (SH) levels, and histopathological parameters were evaluated in the tissue samples. Results: MDA and total SH levels were significantly higher in the IR group than in the control group (p < 0.0001 and p = 0.001, respectively). MDA and total SH levels were significantly lower in the IR-HRS group than in the IR group (p < 0.0001 and p = 0.013, respectively). A histopathological examination revealed that neutrophil infiltration/aggregation, alveolar wall thickness, and total lung injury score were significantly higher in the IR group than in the control group (p < 0.0001, p = 0.001, and p < 0.0001, respectively). Similarly, alveolar wall thickness and total lung injury scores were significantly higher in the IR-HRS group than in the control group (p = 0.009 and p = 0.004, respectively). A statistically significant decrease was observed in neutrophil infiltration/aggregation and total lung injury scores in the IR-HRS group compared to those in the IR group (p = 0.023 and p = 0.022, respectively). Conclusion: HRS at a dose of 20 mg/kg, administered intraperitoneally 30 min before ischemia in rats, reduced lipid peroxidation and oxidative stress, while also reducing IR damage in lung histopathology. We believe that HRS administered to rats prior to IR exerts a lung-protective effect.
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    Investigation of Effects of Propofol and Vitamin C Administration on Hepatic and Renal Tissue in Diabetic Rats
    (Gazi Univ, Fac Med, 2015) Arslan, Mustafa; Bilge, Mustafa; Sezen, Saban Cem; Ozturk, Levent; Isik, Berrin; Comu, Faruk Metin; Yilmaz, Dervis
    Obective: A close relationship between diabetic complications and lipid peroxidation is known. It was shown that in diabetic rat pharmacodynamics and pharmacokinetics of propofol was changed. We aim to investigate effects of application propofol and vitamin C on liver and kidney tissue in diabetic rats. Method: Twenty eight wistar albino rats were randomly divided into 4 study groups. Rats in control group were treated only with saline intra peritonealy. Experimental diabetes was induced with a single dose of streptozotocin (60 mg/kg). In propofol adminastrated diabetic rat group (DP) 150 mg/kg propofol was given intraperitoneally. In both propofol and vitamin C adminastrated rats group (DP+Vit C), 100 mg/kg vitamin C was given before 30 minutes administration of 150 mg/kg propofol. In the diabetic control group (DC) administartion of intraperitoneally saline solution alone to the diabetic rats was achieved. Rats were sacrified and liver and kidney tissue were removed. Liver and renal tissue was obtained for histological and biochemical determination. Antioxidant enzymes SOD, CAT, GST activities and MDA concentration were determined in liver and renal tissue. Results: Liver MDA levels in group DC was found to be significantly higher than DP, DP+Vit C and C groups (p=0.024, p=0.008, p=0.016). Liver SOD activity in group 3 was found to be significantly lower in groups DP+Vit C and C (p=0.011, p=0.038). Liver GST activity in group DP+Vit C was found to be significantly lower when compared with group C (p = 0.011). Liver CAT activity showed no difference among groups. Renal MDA levels in group DC was found to be significantly higher in groups DP+Vit C and C (p=0.016, p=0.010). Renal SOD activity in DC was found to be significantly lower than groups DP, DP+Vit C and C (p=0.028, p=0.019, p=0.009). Renal GST and CAT activity showed no difference among groups. Histopathalogically group DP was more damaged than in group C. Conclusion: Diabetes increased lipid peroxidation and reduced the antioxidant activity. However, application of vitamin C reduced lipid peroxidation and increased antioxidant activity. Results of our study have to be supported other experimental studies.
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    The Effect of Proanthocyanidin on Ischemia-Reperfusion Injury in Skeletal Muscles of Rats
    (Mdpi, 2024) Ozer, Abdullah; Kocak, Basak; Sezen, Saban Cem; Arslan, Mustafa; Kavutcu, Mustafa
    Background and Objectives: Lower limb skeletal muscle ischemia-reperfusion (IR) injury is associated with increased morbidity and mortality, and it is common in several clinical situations such as aortic aneurysms repairment, peripheral arterial surgery, vascular injury repairment, and shock. Although it is generally accepted that oxidative stress mediators have a significant role in IR injury, its precise mechanism is still unknown. Anecdotally, it is sustained not only by structural and functional changes in the organ it affects but also by damage to distant organs. The purpose of this report is to illustrate the effect of proanthocyanidin on IR injury. Materials and Methods: In our study, 18 male Wistar albino rats were used. The subjects were divided into three groups containing six mice each (control, C; ischemia-reperfusion, IR; ischemia-reperfusion and proanthocyanidin; IR-PRO). Intraperitoneal proanthocyanidin was given to the IR and proanthocyanidin groups 30 min before laparotomy, and 1 h ischemia led to these two groups. After one hour, reperfusion started. Muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, muscle oval-central nucleus ratio, leukocyte cell infiltration, catalase enzyme activity, and TBARS were all examined in lower-limb muscle samples after one hour of reperfusion. Results: When skeletal muscle samples were evaluated histopathologically, it was discovered that muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, and leukocyte cell infiltration with oval-central nucleus standardization were significantly higher in the IR group than in the C and IR-P groups. Oval-central nucleus standardization was significantly higher in the IR and IR-PRO groups than in the control group. TBARS levels were significantly higher in the IR group than in the control and IR-PRO groups, while catalase enzyme activity was found to be significantly lower in the IR group than in the control and IR-PRO groups. Conclusions: As a consequence of our research, we discovered that proanthocyanidins administered before IR have a protective impact on skeletal muscle in rats. Further research in this area is required.
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    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; Dursun, Ali Dogan
    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.
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    The effect of silymarin on ischemia-reperfusion injury in skeletal muscles of rats silymarin and ischemia-reperfusion injury
    (Turkish National Vascular and Endovascular Surgery Society, 2024) Ozer, Abdullah; Kocak, Basak; Arslan, Mustafa; Mardin, Baris; Kucuk, Aysegul; Sezen, Saban Cem; Zor, Mustafa Hakan
    Aim: Although the precise process is not entirely elucidated, it is well-known that oxidative stress mediators contribute to ischemia-reperfusion (I/R) injury. The impact of silymarin on I/R injury in many different tissues has been examined. For this purpose, we planned to see the effect of silymarin on muscle tissue in rats subjected to lower extremity I/R injury. Material and Methods: We used 18 male Wistar albino rats weighing 225-275 g. Each of the three groups of rats [Control (C), Ischemia-Reperfusion (I/R), and Silymarin-Ischemia/Reperfusion (S-I/R)] consisted of six rats. Silymarin was administered intraperitoneally 30 minutes before the procedure. (100 mg/kg-1) In Group I/R, the infrarenal abdominal aorta was clamped with a microvascular clamp. The clamp was removed after 120 minutes, and reperfusion was achieved for the next 120 minutes. At the end of the reperfusion period, muscle tissue samples were collected, and Malondialdehyde (MDA), catalase (CAT) enzyme activity levels and histopathological parameters were compared. Results: In the histopathological examination, no degeneration was observed in the muscle fibers in the Group C, while findings of striated muscle damage such as muscle atrophy/hypertrophy, muscle degeneration/congestion, internalization of the muscle nucleus/oval/central nucleus, fragmentation/hyalinization and leukocyte cell infiltration were seen in the Group I/R. In Group S-I/R, muscle atrophy /hypertrophy, internalization of the muscle nucleus/oval/central nucleus, fragmentation/hyalinization, and leukocyte cell infiltration were observed to improve these damaged areas compared to Group I/R. MDA levels in the Group I/R were significantly higher compared to Group C and S-I/R. The activity of the CAT enzyme was much higher in Group I/R compared to Group C. Conclusion: Our study revealed that 100 mg/kg-1 silymarin administered by intraperitoneal injection 30 minutes before ischemia effectively decreased lipid peroxidation, oxidative stress, and the injury caused by I/R in muscle histology in rats. © 2024, Turkish National Vascular and Endovascular Surgery Society. All rights reserved.
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    The effects of amantadine on lung tissue in lower limb ischemia/reperfusion injury model in rats
    (Baycinar Medical Publ-Baycinar Tibbi Yayincilik, 2021) Orhan, Mustafa; Tuna, Ayca Tas; Unal, Yusuf; Arslan, Mustafa; Yazar, Hayrullah; Sezen, Saban Cem; Gozukara, Sezen Irmak
    Background: This study aims to evaluate the effect of amantadine on lung tissue of after lower limb ischemia/reperfusion injury in rats. Methods: A total of 24 Wistar rats were divided into four equal groups including six rats in each: sham group (Group S), amantadine group (Group A), ischemia/reperfusion group (Group I/R), and ischemia/reperfusion + amantadine group (Group I/R-A). All groups underwent a midline abdominal incision. In Groups I/R and I/R-A, the infrarenal abdominal aorta was clamped for 120 min and, then, reperfused for 120 min after removal of the clamp. Amantadine hydrochloride 45 mg/kg was administered intraperitoneally to the rats of Groups A and Group I/R-A 15 min before surgery. At the end of reperfusion period (240 min), all rats were sacrificed, and their lung tissues were obtained. Lung tissue catalase and superoxide dismutase activities and glutathione S-transferase and malondialdehyde levels were analyzed. Lung tissues were examined histopathologically. Results: Catalase activity was lower in Groups A, I/R, and I/R-A compared to Group S. Superoxide dismutase activity was higher in Group I/R than Group S. Superoxide dismutase activity in Groups I/R-A and A decreased, compared to Groups S and I/R. Glutathione S-transferase levels decreased in Groups I/R and A, compared to Group S. Glutathione S-transferase levels in Group I/R-A were higher than Groups I/R and A. The highest level of malondialdehyde was found in Group I/R and the lowest level was found in Group I/R-A. According to histopathological examination, infiltration scores were significantly lower in Group S than Groups I/R and I/R-A (p=0.009 and p=0.011, respectively). The alveolar wall thickening scores in Group I/R were also significantly higher than Groups S and Group A (p=0.001 and p=0.001, respectively). Conclusion: Lung tissue can be affected histopathologically by ischemia/ reperfusion injury and this injury can be reversed by amantadine administration.
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    The role of pomegranate seed oil on kidney and lung tissues in the treatment of sepsis: animal pre-clinical research
    (J Infection Developing Countries, 2023) Arslan, Mustafa; Kucuk, Aysegul; Bozok, Ummu Gulsen; Ergoruen, Aydan Iremnur; Sezen, Saban Cem; Yavuz, Aydin; Kavutcu, Mustafa
    Objectives: Sepsis is a common disease with a high mortality. Decreasing the speed is possible with early and intensive therapy. However, most medicines have been tested, but none has proven effective. Therefore, the study aimed to discover the protective and therapeutic effects of pomegranate seed oil (PSO). Methods: The cecal ligation puncture (CLP) method was used to induce sepsis. The experimental procedure was started with the animals divided haphazardly into four groups: control (C), sepsis (CLP), CLP + low dose PSO (CLP + LD), and CLP + high dose PSO (CLP + HD). First, the cecum was filled with feces. The full cecum was tied under the ileocecal valve for ligation and punctured. At 1 hour after CLP, 0.32 mg/kg and 0.64 mg/kg of PSO were administered. 24 hours after, lung and kidney specimens were collected. Results: Neutrophil infiltration/aggregation and alveolar wall thickness decreased in lung with PSO groups compared with the CLP. The findings for overall lung injury were similar. In renal, all parameters were increased in the CLP compared with C, except for vascular vacuolization and hypertrophy. According to the CLP, all parameters were significantly lower in CLP + HD. Furthermore, glomerular vacuolization, degeneration, and necrosis of tubular cell, dilatation of bowman space, and tubular hyaline cylinders reduced CLP + LD versus CLP. Thiobarbituric acid-reactive substances decreased in lung, with the PSO groups. In addition, superoxide dismutase increased in PSO groups versus CLP. Conclusions: We conclude that the high-dose PSO is especially effective in treating sepsis.