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Öğe Does leflunomide attenuate the sepsis-induced acute lung injury?(Springer, 2008) Ozturk, Erdogan; Demirbilek, Semra; Begec, Zekine; Surucu, Murat; Fadillioglu, Ersin; Kirimhoglu, Hale; Ersoy, M. OzcanThe organ that is affected first and most severely in intraabdominal sepsis is the lung. Oxygen radicals and active neutrophils in the lung are important sources for severe pulmonary inflammation leading to acute lung injury (ALI)/acute respiratory distress syndrome. The aim of this study was to investigate the effects of leflunomide, an immunomodulatory agent, on oxidant/antioxidant status with nitric oxide (NO) level and myeloperoxidase (MPO) activity in rats with sepsis-induced ALI. Fifty male Wistar albino rats were divided into five groups: control, sham, sepsis, leflunomide (10 mg/kg, intragastrically for two doses with an 8 h interval prior to the experiment) and sepsis + leflunomide. After the animals were anesthetized with ketamine and xylazine, the abdominal cavity was opened and ligated just below the ileocaecal valve with 3-0 silk. The antimesentric surface of the cecum was perforated and the cecum was gently compressed until fecal matter was extruded to induce sepsis. None of the rats received antibiotics during the experimental procedures. The experiment was ended 24 h after cecal ligation puncture (CLP) with the cervical dislocation under anesthesia. The lung tissues were removed for analysis of biochemical parameters and light microscopic investigation. The lung superoxide dismutase (SOD), catalase and glutathione peroxidase activities were decreased in the sepsis group as compared to the group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and SOD activity were significantly higher in group sepsis + leflunomide than sham, control, leflunomide and sepsis group (P < 0.05). The lung MPO, malondialdehyde (MDA), protein carbonyl and NO levels were higher in the sepsis group when compared to group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and MPO, MDA and NO levels were higher in the sepsis + leflunomide group than in the sham, control and leflunomide group (P < 0.05). The light microscopic evaluation showed that pulmonary architecture was preserved, and infiltration of neutrophil and edema decreased in sepsis + leflunomide group. The grade of alveolar damage was significantly decreased in sepsis + leflunomide group in comparison with sepsis group (P < 0.05). Our findings suggested that leflunomide attenuated the lung injury after CLP-induced sepsis by inhibition of neutrophils accumulation and increasing endogenous antioxidant capacity.Öğe DOSE DEPENDENT EFFECTS OF CAFFEIC ACID PHENETHYL ESTER ON HEART RATE AND BLOOD PRESSURE IN RATS(Modestum Ltd, 2005) Iraz, Mustafa; Fadillioglu, Ersin; Tasdemir, Seda; Ates, Burhan; Erdogan, SelimAim: Caffeic acid phenethyl ester (CAPE) is one of the major components of honeybee propolis and its structure is similar to flavonoids. The molecular mechanisms of the effects of CAPE on various systems including cardiovascular system have not been known well. The aim of the present study was to investigate the short term dose dependent in vivo cardiovascular effects including heart rate and blood pressure changes induced by CAPE in Sprague Dawley rats. Methods: The rats were anaesthetized and randomly divided into six groups (n: 6 rats) as follows: the first two groups of rats were injected 0.9% NaCl or 10% alcohol; the other groups were injected 1 mg kg(-1), 5 mg kg(-1) 10 mg kg(-1) or 20 mg kg(-1) CAPE i.v. Results: CAPE injection caused decrease in mean blood pressure (MBP) up to 20 sec. for 1 mg CAPE group and up to 2 min for 5 and 10 mg CAPE groups. On the other hand, heart rate (HR) was found to be decreased up to 10 min. for 10 mg CAPE group Conclusion: CAPE causes decrease in both HR and MBP and may affect conduction velocity and contractility in heart due to possible effects on neuronal transmission.Öğe Effect of leflunomide on liver regeneration after partial hepatectomy in rats(Springer, 2010) Karaman, Abdurrahman; Kirimlioglu, Hale; Tas, Erkan; Karadag, Nese; Gulsul, Cebrail; Fadillioglu, Ersin; Demircan, MehmetPartial hepatectomy (PH) can be an inevitable surgical therapy in some conditions, such as hepatic malignancies, trauma or partial liver transplantation. Its capacity for regeneration distinguishes the liver from other essential organs. Regeneration is a complex process involving growth factors, cytokines, transcription factors, hormones, and oxidative stres products. In the event of ineffective or total absent liver regeneration, the lifethreatening picture of acute liver failure may supervene. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic regeneration after PH in Wistar Albino rats. Thirty-five Wistar albino rats were divided into five groups: group 1, control; group 2, sham; group 3, drug control (was treated with leflunomide 10 mg/kg/d/i.g.); group 4, PH; group 5, PH + leflunomide. As for PH, approximately 70% of the rat liver was surgically removed under general anesthesia. On postoperative day 3, all rats were humanely killed. Catalase (CAT), superooxide dismutase (SOD) and myeloperoxidase (MPO) activities with malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were determined in remnant liver tissue. Inflammatory process and liver regeneration were evaluated with H&E and KI67, respectively. The tissue levels of MDA, PC and MPO were lower in group 5 than levels in group 1. PH significantly decreased the enzymatic activity of CAT (p < 0.05) and SOD. This reduction was significantly improved by the treatment with leflunomide. Histopathologically the enhancement of the liver parenchymal regeneration in the group 5 was significantly greater than the group 4. The findings imply that oxidative stress products play a preventive role in liver regeneration after PH and leflunomide ameliorates the regeneration probably by the radical scavenging and antioxidant activities.Öğe Effects of caffeic acid phenethyl ester on thioacetamide-induced hepatic encephalopathy in rats(Pergamon-Elsevier Science Ltd, 2010) Fadillioglu, Ersin; Gursul, Cebrail; Iraz, MustafaHepatic encephalopathy (HE) is a major neurological complication secondary to severe liver failure. The aim of the present study was to examine the possible neuroprotective effects of caffeic acid phenethyl ester (CAPE) with or without laxative treatment against thioacetamide-induced HE by investigating behavioral and motor activities in rats as well as blood ammonia level and oxidant-antioxidant parameters of cortex, brain stem and cerebellum. After induction of HE by thioacetamide, the rats were treated with lactulose, CAPE (CAPE treatment was started one day before the first dose of thioacetamide) or CAPE plus lactulose. The behavioral and motor scales were measured at the 54th hour after the first thioacetamide injection, the blood samples and brains were taken under anesthesia at the 60th hour for biochemical analysis. The survival rates were 37.5% in HE group, 70% in HE + lactulose group, 80% in HE + CAPE group, and 100% in HE + CAPE + lactulose group. Increased ammonia, ALT and AST levels in blood along with impaired sensory-motor behavior tests were reversed to proximate control values in CAPE + lactulose treated group. There were increased lipid peroxidation and protein oxidation and decreased antioxidant enzyme activities in almost all brain parts of HE group. CAPE or lactulose treatment alone ameliorated those oxidant and antioxidant parameters; however, CAPE treatment together with lactulose reversed them to almost control level. In conclusion, thioacetamide-induced HE injury in rats was reversed almost fully by CAPE and laxative combination. There was no death in CAPE and laxative treated group animals and it may be due to the direct neuroprotective effect of CAPE together with the prevention of the body from ammonia production. (C) 2010 Elsevier Inc. All rights reserved.Öğe The Effects of Nitric Oxide on Rat Stomach Injury Induced by Acetylsalicylic Acid(Tubitak Scientific & Technological Research Council Turkey, 2009) Yagmurca, Murat; Ucar, Muharrem; Fadillioglu, Ersin; Erdogan, Hasan; Ozturk, FeralAim: Acetylsalicylic acid (ASA, aspirin), which is one of the most frequently used drugs in the world. causes severe gastric mucosal injury. Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS). NOS can be inhibited by N omega-nitro-L-arginine methyl ester (L-NAME) and stimulated by supplementing the diet with L-arginine (L-Arg). The aim of this study was to investigate the role of NO on gastric mucosal injury induced by ASA. Materials and Methods: Male Sprague-Dawley rats were divided into seven groups: control, ASA, ASA+L-NAME, ASA+L-Arg, ASA+L-Arg+L-NAME, only L-NAME. and only L-Arg groups. After administration of the drugs, the rats were decapitated and their stomachs were removed and fixed in 10% neutral-buffered formalin solution. Results: Mucosal erosion, intramucosal hemorrhage, inflammatory cell infiltration, gland cell detachment, and necrosis were observed in the ASA group. It was demonstrated that L-Arg administration decreased the gastric mucosal injury, whereas L-NAME administration increased the extent and severity of the gastric injury induced by ASA. L-Arg or L-NAME administration alone did not affect gastric mucosa. Conclusions: We concluded that NO may have protective effects on gastric mucosal injury induced by ASA.Öğe Effects of Tolterodine and Trospium Chloride on Renal Damage Induced by Partial Upper Urinary Tract Obstruction(Elsevier Science Inc, 2013) Karaman, Abdurrahman; Samdanci, Emine; Sayin, Sadegul; Karabulut, Ismail; Fadillioglu, ErsinOBJECTIVE To examine the efficacy of trospium chloride and tolterodine on the renal parenchymal inflammatory process and upper urinary dilation in rats with chronic partial upper urinary tract obstruction. MATERIALS AND METHODS A total of 32 rats were divided into 4 groups: group 1, control; group 2, obstruction; group 3, obstruction plus tolterodine; and group 4, obstruction plus trospium chloride. In all groups, except for group 1, partial upper urinary tract obstruction was induced by embedding the upper quarter of the right ureter into the psoas muscle for 14 days. At the end of the experiment, the rats were killed. The catalase, malondialdehyde, and protein carbonyl levels were determined in renal tissue. Tubular dilation and parenchymal inflammation were evaluated using hematoxylin-eosin staining. Smooth muscle actin and cytoglobin were examined with immunohistochemical staining. RESULTS The obstruction group demonstrated severe pelvic dilation and parenchymal inflammation and increased smooth muscle actin staining in the wall of upper urinary tract (P < .05). The treatment of the rats with tolterodine and trospium chloride markedly attenuated the inflammatory alterations and reduced tubular dilation. This treatment also reduced elevated oxidative stress product levels and restored the depleted renal antioxidant enzyme. CONCLUSION These findings imply that increased renal pelvic pressure can contribute to renal parenchymal injury in chronic pelvic upper urinary tract obstruction. Antimuscarinic medications such as tolterodine and trospium chloride exert renoprotective effects, probably by prevention of pelvic pressure increases. UROLOGY 82: 194-200, 2013. (C) 2013 Elsevier Inc.Öğe Elements Levels and Glucose-6-Phosphate Dehydrogenase Activity in Blood of Patients with Schizophrenia(Kare Publ, 2012) Kaya, Burhanettin; Akdag, Nihal; Fadillioglu, Ersin; Taycan, Serap Erdogan; Emre, Mehmet H.; Unal, Suheyla; Sayal, AhmetObjectives: Glucose-6-phosphate dehydrogenase (G6PD) is the rate limiting enzyme of the hexose monophosphate cascade which plays role in the synthesis of nucleotide, reduced glutathion, fatty acid and cholesterol precursors. At the same time, it is an important enzyme for neuronal development during and after fetal life and for neurotransmitters. Serum elements are necessary for neuronal development and synthesis and activity of enzymes and hormones. The aim of this study was to compare serum levels of some elements and G6PD enzyme activity in schizophrenic patients with those in healthy individuals. Methods: This study involved blood serum analysis of 32 schizophrenia patients and 32 age-and sex-matched healthy controls. Copper, zinc, iron, magnesium levels were determined with a double lighted, deuterium sourced, background proof reading fire atomic spectrophotometer and in order to determine aluminum and manganese levels, a graphite tube atomizer spectroscope was used. G6PD enzyme activity was analyzed by the Glock and Mclean Method. Results: This analysis revealed higher levels of G6PD activity, copper, iron, magnesium and aluminum in schizophrenia patients compared to controls, whereas zinc and manganese levels showed a decreasing trend on the contrary. Discussion: The higher levels of G6PD activity in schizophrenic patients is not consistent with the literature in general. It is considered that results on G6PD and element levels may be explained as the effects of specific hormones, antipsychotic medications, or by schizophrenia itself. Conclusion: The elements we investigated and G6PD are important for the antioxidant system. Thus changing levels of elements in patients with schizophrenia may lead to disturbed functions of antioxidant enzymes and G6PD. Further researches on this subject conducted with larger and drug naive patient groups are needed.Öğe Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus(Pharmaceutical Soc Korea, 2008) Fadillioglu, Ersin; Kurcer, Zehra; Parlakpinar, Hakan; Iraz, Mustafa; Gursul, CebrailOxidative stress may have a role in liver damage after acute renal injury due to various reasons such as ischemia reperfusion (IR). Diabetes mellitus (DM) is an important disease for kidneys and may cause nephropathy as a long term complication. The aim of this study was to investigate protective effect of melatonin, a potent antioxidant, against distant organ injury on liver induced by renal IR in rats with or without DM. The rats were divided into six groups: control (n=7), DM (n=5), IR (n=7), DM+IR (n=7), melatonin+IR (Mel+IR) (melatonin, 4 mg/kg during 15 days) (n=7), and Mel+DM+IR groups (n=7). Diabetes developed 3 days after single i.p. dose of 45 mg/kg streptozotocin. After 15 day, the left renal artery was occluded for 30 min followed 24 h of reperfusion in IR performed groups. DM did not alter oxidative parameters alone in liver tissue. The levels of malondialdehyde, protein carbonyl and nitric oxide with activities of xanthine oxidase and myeloperoxidase were increased in liver tissues of diabetic and non-diabetic IR groups. Nitric oxide level in DM was higher than control. The activities of catalase and superoxide dismutase were increased in IR groups in comparison with control and DM. ALT and AST levels were higher in IR and DM+IR groups than control and DM. Melatonin treatment reversed all these oxidant and antioxidant parameters to control values as well as serum liver enzymes. We concluded that renal IR may affect distant organs such as liver and oxidative stress may play role on this injury, but DM has not an effect on kidney induced distant organ injury via oxidant stress. Also, it was concluded that melatonin treatment may prevent liver oxidant stress induced by distant injury of kidney IR.Öğe N Sup Omega Nitro-L-Arjinin Metil Ester Ile Indüklenen Hipertansiyonlu Siçanlarin Renal Doku Ksantin Oksidaz Ve Adenozin Deaminaz Aktiviteleri(İnönü Üniversitesi Tıp Fakültesi Dergisi, 2002) Fadillioglu, Ersin; Erdogan, Hasan; Emre, Memet HanifiHipertansiyon böbrek fonksiyonlarini negatif yönde degistirebilir. Pürin metobolizmasi hipertansiyondan dolayi olan kan damarlaridaki daralmadan ve artan kalp atim hacminden etkilenebilir. Nitrik oksit sentazin (NOS) N sup omega Nitro-L-Arjinin Metil Ester (L-NAME) ile inhibisyonu siçanlarda hipertansiyona yol açar. Bu çalismanin amaci NOS inhibisyonu sonrasi siçanlarda renal doku adenozin deaminaz (AD) ve ksantin oksidaz (XO) aktivitelerini arastirmakti. Siçanlar üç gruba ayrildi; biri kontrol ve digerleri 15 gün süreyle içme sularinda 100 veya 500 mg/L L-NAME uygulanan çalisma gruplariydi. Yukarda açiklanan uygulamanin sonunda, anesteziye edilen siçanlarda karotid arter kanülasyonu yoluyla arteryel kan basinçlari ölçüldü. Renal dokuda AD ve XO aktiviteleri ölçüldü. Sistolik kan basinçlari L-NAME gruplarinda anlamli artis gösterdi. L-NAME gruplarindaki XO aktivitesi, kontrol grubuyla karsilastirildiginda anlamli olarak artmisti. AD aktiviteleri de L-NAME gruplarinda artmis olmasina karsin, bu artis anlamli bulunmadi. 100 mg ve 500 mg L-NAME gruplari arasinda XO ve AD aktiviteleri açisindan anlamli fark yoktu. Sonuçta, L-NAME ile indüklenen hipertansiyonun pürin nükleotidlerinde artisa neden oldugu kanisina vardik. Böylece, artmis XO ve AD enzim aktiviteleri sonucu birikmis pürin nükleotidleri renal dokudan uzaklastirilabilinir.Öğe Protective effect of leflunomide against oxidative intestinal injury in a rodent model of sepsis(Academic Press Inc Elsevier Science, 2014) Ozturk, Erdogan; Surucu, Murat; Karaman, Abdurrahman; Samdanci, Emine; Fadillioglu, ErsinBackground: Sepsis is defined as an uncontrolled inflammatory response in a host. The process may lead to severe sepsis, multisystem organ failure and even death. Leflunomide has important immunomodulatory and anti-inflammatory effects, which may mitigate host response to bacterial translocation. The goal of our study was to measure the effects leflunomide administration had on a variety of biochemical markers upregulated in systemic inflammatory response syndrome, sepsis, and multiple organ failure syndrome. Materials and methods: Wistar albino type rats were randomly divided into five groups: control, sham, leflunomide, sepsis, and sepsis + leflunomide. Sepsis was achieved by means of the cecal ligation and puncture method. Leflunomide 2 x 10 mg/kg/d was administered before the experiment. At the end of 24 h, the tissue levels of superoxide dismutase, catalase activity, malondialdehyde, nitric oxide, and protein carbonyl were measured. Results: The level of the bowel superoxide dismutase and catalase levels of the sepsis group is significantly lower than those of the control, sham, and leflunomide groups (P < 0.05). Malondialdehyde, nitric oxide, and protein carbonyl levels are significantly higher in sepsis compared with other groups (P < 0.05). Conclusions: Leflunomide's prevention of protein and lipid peroxidation was observed in septic bowel tissue. Use of leflunomide could have protective effects against both the onset and the progressive stages of sepsis. Crown Copyright (c) 2014 Published by Elsevier Inc. All rights reserved.
