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Öğe Alkolün oluşturduğu serbest radikaller üzerine ibuprofen ve erüsik asidin etkileri(Trakya Üniversitesi, 2000) Akpolat, Meryem; Altuğ, Tuncay; Dökmeci, Dikmen7. ÖZET Bu çalışmada, antioksidan özellikleri araştırma aşamasında olan steroid olmayan antiinflamatuvar ilaçlar arasında yer alan ve spesifik olarak siklooksijenaz-1 enzim inhibisyonu yapan ibuprofen ile polienoik yağ asitleri içerisinde, tekli doymamış yağ asitleri grubunda yer alan erusik asit (C22A13) kullanılmıştır. İbuprofen ve erusik asitin 20 gün uygulanmasının ardından verilen akut yüksek doz etanolun karaciğer ve plazmadaki antioksidan enzimler ve lipid peroksidasyonu üzerine etkileri incelenmiştir. Bu amaçla ortalama ağırlığı 250-300 g olan 3.5-4 aylık 32 adet Sprague Dawley erkek sıçan kullanılarak dört grup oluşturulmuştur. Her üç deney grubuna 20 gün boyunca sırasıyla ibuprofen (17 mg/kg), erusik asit (100 mg/sıçan), ibuprofen+erusik asit gavaj yolu ile uygulanmış, kontrol grubuna ise 20 gün boyunca İmL çeşme suyu gavaj yolu ile verilmiştir. 20. Gün tüm grupların gavaj lan yapıldıktan 2 saat sonra 6 g/kg etanol dozu ikiye bölünerek 2 saat ara ile 4 gruba da etanol gavaj yolu ile verilmiştir. Uygulamaların bitiminden 1 saat sonra hayvanlar sakrifiye edilerek heparinize kan örnekleri alınmış ve karaciğer dokusu perfüze edilerek çıkarılmıştır. Plazmaları ayrılan kan örnekleri ile karaciğer dokusu -70 °C'de saklanmıştır. Biyokimyasal incelemeler için doku homojenatları hazırlanmış ve plazma ve karaciğer malondialdehit (MDA) düzeyleri ile karaciğer süperoksid dismutaz (SOD), katalaz (CAT) aktiviteleri ölçülmüştür. Etanol gerek plazmada gerek karaciğer dokusunda MDA düzeylerinde belirgin bir artışa yol açmıştır. İbuprofen, erusik asit ve ibuprofen + erusik asit MDA düzeylerini kontrole göre düşürmüştür. Erusik asit MDA düzeylerini düşürmede daha etkili bulunmuştur. Etanol, ibuprofen ve erusik asitin antioksidan savunma enzimleri üzerine etkisi incelendiğinde; SOD aktivitesi kontrol grubunda diğer gruplara göre daha düşük bulunmuştur, bu da etanolun SOD aktivitesini düşürdüğünün bir kanıtıdır. İbuprofen, erusik asit ve ibuprofen + erusik asit SOD aktivitesini kontrole göre artırmıştır. Bu artış en fazla ibuprofen grubunda göze çarpmaktadır. CAT aktivitesi kontrol grubunda diğer gruplara nazaran artmıştır, bu da yüksek dozda etanol 64uygulamasının karaciğer CAT enzim aktivitesini artırdığını göstermektedir. İbuprofen ve erusik asit CAT aktivitesini kontrole göre düşürmüştür. Çalışmamızın bulguları etanolun oksidan bir madde olduğu yönündeki bilgilere uygun düşmektedir. Bulgularımız ibuprofen ve erusik asitin antioksidan özellik taşıdığı yönündeki düşüncelerimizi desteklemektedir. Anahtar kelimeler: etanol, serbest radikal, ibuprofen, erusik asit, antioksidan. 65Öğe Effects of Curcumin on Apoptosis and Oxidoinflammatory Regulation in a Rat Model of Acetic Acid-Induced Colitis: The Roles of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase(Mary Ann Liebert, Inc, 2013) Topcu-Tarladacalisir, Yeter; Akpolat, Meryem; Uz, Yesim Hulya; Kizilay, Gulnur; Sapmaz-Metin, Melike; Cerkezkayabekir, Aysegul; Omurlu, Imran KurtThe present study evaluated the effects of curcumin on epithelial cell apoptosis, the immunoreactivity of the phospho-c-Jun N-terminal kinase (JNK) and phospho-p38 mitogen-activated protein kinases (MAPKs) in inflamed colon mucosa, and oxidative stress in a rat model of ulcerative colitis induced by acetic acid. Rats were randomly divided into three groups: control, acetic acid, and acetic acid + curcumin. Curcumin (100 mg/kg per day, intragastrically) was administered 10 days before the induction of colitis and was continued for two additional days. Acetic acid-induced colitis caused a significant increase in the macroscopic and microscopic tissue ranking scores as well as an elevation in colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, and the number of apoptotic epithelial cells in colon tissue compared to controls. In the rat colon, immunoreactivity of phospho-p38 MAPK was increased, whereas the phospho-JNK activity was decreased following the induction of colitis. Curcumin treatment was associated with amelioration of macroscopic and microscopic colitis sores, decreased MPO activity, and decreased MDA levels in acetic acid-induced colitis. Furthermore, oral curcumin supplementation clearly prevented programmed cell death and restored immunreactivity of MAPKs in the colons of colitic rats. The results of this study suggest that oral curcumin treatment decreases colon injury and is associated with decreased inflammatory reactions, lipid peroxidation, apoptotic cell death, and modulating p38- and JNK-MAPK pathways.Öğe Gamma radyasyonun ileum kadehsi hücrelerinde oluşturduğu hasarlara karşı curcumin ve c vitamininin koruyucu etkilerinin ışık ve elektron mikroskobik düzeylerde incelenmesi(2007) Akpolat, Meryem; Kanter, MehmetGastrointestinal kanal, radyasyonun etkilerine karşı en duyarlı organlardan biridir. İntestinal mukoza üzerindeki iyonize radyasyonun sitotoksik etkisinin, oksidatif stres ile ilgili olduğu bilinmektedir. Antioksidan maddelerin, radyasyon hasarına karşı yararlı etkiye sahip olduğu ileri sürülmektedir. Sıçanlar üzerinde yapılan bu çalışmada; farklı dozlarda gamma radyasyona bağlı, ileum kadehsi hücrelerinde meydana gelen hasarlara karşı, curcumin ve C vitamininin koruyucu etkilerinin olup olmadığının ışık ve elektron mikroskobik düzeylerde incelenmesi amaçlandı. Hayvanlar biri kontrol 6'sı deney grubu olmak üzere toplam 7 gruba ayrıldı. Radyasyon hasarı oluşturmak amacıyla, kontrol grubu dışındaki deneklerin batın bölgelerine 5 Gy'lik gamma ışını verildi. Işınlamadan sonraki 4. günde, III., V. ve VII. grup deneklere ikinci kez aynı dozda ışın uygulandı. Radyasyon hasarını önleyebilmek amacı ile IV. ve V. grup deneklere, ışınlamadan 10 gün önce başlayıp sakrifikasyon zamanlarına kadar 100 mg/kg curcumin dimetilsülfoksit içinde çözülerek intragastrik yoldan; VI. ve VII. grup deneklere de, aynı sürelerde intraperitoneal yoldan 100 mg/kg C vitamini verildi. I., II., IV. ve VI. grup deneklerden, birinci ışınlamadan sonra 4. günde, III., V. ve VII. grup deneklerden de ikinci ışınlamadan sonraki 4. günde, anestezi altında alınan ileum biyopsi materyalleri ışık ve elektron mikroskobik gözlemlerimiz için işlemlendirildi. Çalışmamızda, hem tek hem de iki doz 5 Gy gamma radyasyonun ileum mukozasında hasara sebep olduğu, kadehsi hücrelerin şekil ve yerleşimlerinde bozukluklara yol açtığı gözlendi. Özellikle radyasyona bağlı olarak sayıları artan kadehsi hücrelerin mukozadaki düzensiz dağılımları dikkat çekiciydi. Elektron mikroskobik düzeyde, hücreler arası sahada genişlemeler, mikrovilluslarda bozulmalar, mitokondriyal hasar ve özellikle granüllü endoplazmik retikulum sisternalarında görülen dilatasyon en belirgin değişiklikler olarak saptandı. Radyasyona bağlı kadehsi hücrelerde meydana gelen hasarların önlenmesinde, curcuminin etkili olduğu, C vitamininin ise uyguladığımız dozda yeterli koruma sağlamadığı tespit edildi. Sonuç olarak; curcuminin radyoterapi esnasında, intestinal mukozayı koruyarak, tedavi kazancını artırabileceği ve kliniğe fayda sağlayabileceği kanısına varıldı. Anahtar Kelimeler: gamma-radyasyon, ileum, kadehsi hücre, curcumin, C vitamini, sıçan.Öğe N-acetylcysteine counteracts oxidative stress and protects alveolar epithelial cells from lung contusion-induced apoptosis in rats with blunt chest trauma(Springer, 2014) Topcu-Tarladacalisir, Yeter; Tarladacalisir, Taner; Sapmaz-Metin, Melike; Karamustafaoglu, Altemur; Uz, Yesim Hulya; Akpolat, Meryem; Cerkezkayabekir, AysegulThe aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs of rats following blunt chest trauma. The rats were randomly divided into three groups: control, contusion, and contusion + NAC. All the rats, apart from those in the control group, performed moderate lung contusion. A daily intramuscular NAC injection (150 mg/kg) was given immediately following the blunt chest trauma and was continued for two additional days following cessation of the trauma. Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde (MDA) level, histopathology, and epithelial cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active caspase-3 immunostaining. In addition, we immunohistochemically evaluated the expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest trauma-induced lung contusion resulted in severe histopathological injury, as well as an increase in the MDA level and in the number of cells identified on TUNEL assay together with active caspase-3 positive epithelial cells, but a decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC treatment effectively attenuated histopathologic, peroxidative, and apoptotic changes, as well as reducing alterations in SP-D expression in the lung tissue. These findings indicate that the beneficial effects of NAC administrated following blunt chest trauma is related to the regulation of oxidative stress and apoptosis.Öğe Protection by L-carnitine against radiation-induced ileal mucosal injury in the rat: Pattern of oxidative stress, apoptosis and cytokines(Taylor & Francis Ltd, 2013) Akpolat, Meryem; Gulle, Kanat; Topcu-Tarladacalisir, Yeter; Oz, Zehra Safi; Bakkal, Bekir Hakan; Arasli, Mehmet; Turkcu, Ummuhani OzelPurpose : In this study, we tested the effects of L-carnitine (LC) on radiation-induced ileal mucosal damage. Materials and methods : Thirty Wistar albino rats were divided into five groups. The control group received physiological saline intraperitoneally (i.p.). Radiation-1 and radiation-2 groups received whole-body X-irradiation of 8.3 Gy as a single dose. These groups were sacrificed at the 6th hour and 4th day after irradiation, respectively. The Radiation-1 + LC and the radiation-2 + LC groups received the same dose irradiation plus a daily dose of 200 mg/kg LC. LC was applied one day before and for four days after irradiation. Results : The levels of serum monocyte chemotactic protein-1 (MCP-1) and interferon gamma (IFN-gamma) were significantly higher in the radiation groups when compared with the control. Treatment with LC decreased the serum MCP-1 and IFN-gamma levels considerably. In the radiations groups, the Chiu score was significantly elevated compared with that of the control group. However, LC administered prior to the irradiation reduced the severity of mucosal damage. The number of apoptotic cells of the ileal crypt in the irradiated rats increased from the 6th hour after irradiation and then decreased at 4th day. Conclusions : Our data demonstrated that LC may be beneficial to radiation enteritis.Öğe The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats(Galenos Publ House, 2012) Ozgen, Seher Cimen; Dokmeci, Dikmen; Akpolat, Meryem; Karadag, Cetin Hakan; Gunduz, Ozgur; Erbas, Hakan; Benian, OmerObjective: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. Material and Methods: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. Results: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. Conclusion: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.Öğe Protective Effect of Flaxseed Oil on Renal Injury in Hyperlipidaemic Rats: The Effect of Flaxseed Oil on Hyperlipidaemia(Wiley, 2011) Akpolat, Meryem; Kanter, Mehmet; Topcu-Tarladacalisir, Yeter; Aydogdu, NurettinThis study evaluated the possible effects of flaxseed oil on renal damage associated with hyperlipidaemic rats. Wistar albino male rats were divided into three groups. Group I was fed with a pellet chow. Group II was fed with a high cholesterol diet (HCD) consisting of 5% cholesterol and 0.35% cholic acid added to the pellet chow. Group III was fed with the same HCD, but were orally treated with a dose of 15 mg/kg body wt/day flaxseed oil. Flaxseed oil treatment started 1 week before and continued throughout the 22 weeks of the HCD. At the end of the experiment, renal tissue and blood samples were collected. The biochemical and histopathological findings confirmed renal damage in hypercholesterolaemia conditions. Flaxseed oil reduced the hypercholesterolaemia-induced increase in the serum levels of total cholesterol, LDL and urea. Oil red O stain revealed that lowered serum lipid was accompanied by a decreased deposition of neutral lipid. Flaxseed oil effectively reversed these abnormalities, verifying the protective effects of flaxseed oil in ameliorating renal injuries associated with hypercholesterolaemia. Copyright (C) 2010 John Wiley & Sons, Ltd.Öğe Protective effect of sildenafil on liver injury induced by intestinal ischemia/reperfusion(W B Saunders Co-Elsevier Inc, 2013) Inan, Mustafa; Uz, Yesim Hulya; Kizilay, Gulnur; Topcu-Tarladacalisir, Yeter; Sapmaz-Metin, Melike; Akpolat, Meryem; Aydogdu, NurettinBackground: This study evaluated the protective effect of sildenafil on liver injury induced by intestinal ischemia-reperfusion. Methods: Forty female Sprague Dawley rats were divided into 4 groups: sham-control (SC), ischemia (I), ischemia-reperfusion (IR), and ischemia-reperfusion+ sildenafil (SIL; sildenafil gavaged at 50 mg/kg before operating). A 2-h ischemia-reperfusion was performed by clamping the superior mesenteric artery. Liver function, plasma alanine (ALT) and aspartate (AST) aminotransferase, and intestinal and liver malondialdehyde (MDA) were measured at the end of the experiment. Intestinal and liver tissue damage was examined by histology. Liver samples were immunologically stained for endothelial nitric oxide synthase (eNOS) and proliferating cell nuclear antigen (PCNA). Results: The ALT and AST levels were highest in the IR group and were lower in the SIL group (p<0.05). Intestinal MDA levels were statistically higher in the IR group than in the SC, I and SIL groups. Liver MDA levels were significantly higher in the IR group than in the I and SC groups (p<0.05) and higher than in the SIL group (p>0.05). Intestinal damage based on Chiu scoring was more severe in the IR than in the SIL group (p<0.05). Sildenafil reduced damage and also increased eNOS and PCNA immunoreactivity in liver tissue. Conclusions: Sildenafil shows a protective effect on intestinal ischemia-reperfusion-induced liver injury, possibly by decreasing vascular resistance through increased nitric oxide levels. (C) 2013 Elsevier Inc. All rights reserved.Öğe Protective effects of curcumin against gamma radiation-induced ileal mucosal damage(Springer Heidelberg, 2009) Akpolat, Meryem; Kanter, Mehmet; Uzal, Mustafa CemThe major objective of this study was to test curcumin as a potential radioprotectant for the ileum goblet cells of the rat. Wistar albino rats were used in the study. Group A was the control group and group B was the single dose radiation group. Group C was the two dose radiation group (4 days interval). The rats in groups D and E were given a daily dose of 100 mg/kg of curcumin for 14 and 18 days, respectively. During the curcumin administration period, the rats in group D were exposed to abdominal area gamma (gamma)-ray dose of 5 Gy on the 10th day and group E was exposed to same dose radiation on the 10th and 14th day. Irradiation and treatment groups were decapitated on the 4th day after exposure to single or two-dose irradiation and ileum tissues were removed for light and electron microscopic investigation. Single or two dose 5 Gy gamma-irradiation caused a marked intestinal mucosal injury in rats on the 4th day. Radiation produced increases in the number of goblet cells. Curcumin appears to have protective effects against radiation-induced damage, suggesting that clinical transfer is feasible.Öğe Protective Effects of Ibuprofen and L-Carnitine Against Whole Body Gamma Irradiation-Induced Duodenal Mucosal Injury(Galenos Publ House, 2011) Akpolat, Meryem; Topcu-Tarladacalisir, Yeter; Dokmeci, Dikmen; Turan, Fatma Nesrin; Uzal, Mustafa CemObjective: Ibuprofen and L-carnitine have been demonstrated to provide radioprotective activity to the hamster against whole body sublethal irradiation. The purpose of this study is to test those antioxidant drugs, each of which has the capacity of inhibiting mucosal injury, as topical radioprotectants for the intestine. Material and Methods: The male hamsters were divided into the following four groups (n=6): group 1: control group, received saline, 1 ml/100 g by gavage, as placebo. Group 2: irradiated-control group, received whole body irradiation of 8 Gy as a single dose plus physiological saline. The animals in groups 3 and 4 were given a daily dose of 10 mg/kg of ibuprofen and 50 mg/kg of L-carnitine for 15 days respectively, before irradiation with a single dose of 8 Gy. Twenty-four hours after radiation exposure, the hamsters were sacrificed and samples were taken from the duodenum, and the histopatological determinations were carried out. Results: Morphologically, examination of the gamma irradiated duodenum revealed the presence of shortening and thickening of villi and flattening of enterocytes, massive subepithelial lifting. Pretreatment of ibuprofen and L-carnitine with irradiation reduced these histopathological changes. Conclusion: Ibuprofen and L-carnitine administrated by the oral route may be a good radioprotector against small intestinal damage in patients undergoing radiotherapy.Öğe Protective effects of the volatile oil of Nigella sativa seeds on ?-cell damage in streptozotocin-induced diabetic rats: a light and electron microscopic study(Springer, 2009) Kanter, Mehmet; Akpolat, Meryem; Aktas, CevatThe aim of this study was to evaluate the possible protective effects of the volatile oil of Nigella sativa (NS) seeds on insulin immunoreactivity and ultrastructural changes of pancreatic beta-cells in STZ-induced diabetic rats. STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. The rats in NS treated groups were given NS (0.2 ml/kg) once a day orally for 4 weeks starting 3 days prior to STZ injection. To date, no ultrastructural changes of pancreatic beta-cells in STZ induced diabetic rats by NS treatment have been reported. Islet cell degeneration and weak insulin immunohistochemical staining was observed in rats with STZ-induced diabetes. Increased intensity of staining for insulin, and preservation of beta-cell numbers were apparent in the NS-treated diabetic rats. The protective effect of NS on STZ-diabetic rats was evident by a moderate increase in the lowered secretory vesicles with granules and also slight destruction with loss of cristae within the mitochondria of beta-cell when compared to control rats. These findings suggest that NS treatment exerts a therapeutic protective effect in diabetes by decreasing morphological changes and preserving pancreatic beta-cell integrity. Consequently, NS may be clinically useful for protecting beta-cells against oxidative stress.Öğe Vitamin C protects against ionizing radiation damage to goblet cells of the ileum in rats(Elsevier Gmbh, Urban & Fischer Verlag, 2008) Kanter, Mehmet; Akpolat, MeryemThe aim of the present study was to evaluate the radioprotective effect of vitamin C on gamma-radiation-induced damage to goblet cells of the ileum. Thirty mate Wistar albino rats weighing between 250 and 300 g were randomized into the following study groups: I, control; II, single dose radiation treated; III, two dose radiation treated with a 4-day interval between doses; IV, single dose radiation treated with vitamin C; V, two dose radiation treated with vitamin C. Each group contained six animals. The rats in groups Wand V were given a daily dose of 100 mg/kg of vitamin C for 14 and 18 days, respectively. During the vitamin C administration period, the rats in group IV were exposed in the abdominal area to a gamma-ray dose of 5 Gy on day 10 and group V was exposed to same dose of radiation on days 10 and 14. Irradiation and treatment groups were decapitated 4 days after exposure to single or two dose irradiation and ileum tissues were removed for tight and electron microscopic investigation. Single or two dose gamma-irradiation caused a marked intestinal, mucosal injury in rats. Radiation produced increases in the number of goblet cells. Using transmission electron microscopy, extensions in the area between the cells, disorders in the microvilli, mitochondrial damage and endoplasmic reticulum (ER) cisternae dilatation were observed. Antioxidant treatment with vitamin C prior to irradiation provided protection against intestinal damage. (c) 2008 Elsevier GmbH. All rights reserved.
