Histologic examination of the protective effect of vitamin E and C in cisplatin-induced hepatotoxicity

Amaç: Bu çalışmada, bir antineoplastik ajan olan cisplatinin kronik ygulandığnda yol açtığ karaciğer hasarı ve bu hasara karşı E ve C vitaminlerinin ne ölçüde koruma sağlayacağı ıhistolojik olarak incelendi. Çalışma Planı: Çalışmada, 24 adet Wistar albino cinsi erkek sıçan altı.arlı dört gruba ayrıldı. Kontrol grubu dışındaki (grup 1) deneklere üç ay boyunca, ayda bir kez 5 mg/kg cisplatin intravenöz yolla verildi. Grup 3 ve 4’teki deneklere ise ayrıca, her gün intramusküler yolla sırasıyla 5 mg/kg E vitamini ve 8 mg/kg C vitamini verildi. Deney süresinin sonunda, tüm deneklerin karaciğer materyalleri alınarak ışık ve elektron mikroskobisi ile incelendi. Bulgular: Kontrol grubu deneklerde normal yapıda karaciğer dokusu gözlendi. İkinci grupta Remak kordonları nda düzensizleşme, V. centrolobularis’e yakın sinüzoidlerde genişleme ile birlikte bazal membranlarda kalınlaşma, portal sahalarda ise lenfosit infiltrasyonu görüldü. Üçüncü grupta morfolojik hasarın büyük oranda azaldığı, çoğu portal sahada lenfosit infiltrasyonunun ortadan kalktığı dördüncü grupta ise düzelmenin daha da belirginleşerek portal saha infiltrasyon bölge sayısının hem seyreldiği hem de infiltrasyon hücre sayısının çok azaldığı görüldü. Sonuç: Farklı özelliklere sahip antioksidanların cisplatinin epatotoksisitesinin azalmasına yardımcı olarak klinik uygulamaya katkıda bulunacağısonucuna varıldı.Objectives: We investigated the morphologic changes showing hepatocellular damage caused by the chronic use of cisplatin, an antineoplastic agent, and the protective effect of vitamins E and C. Study Design: Twenty-four Wistar albino male rats were randomly assigned to four groups, equal in number,to receive intravenous 5 mg/kg of cisplatin once a month for three months except for the control rats (group 1). The rats in group 3 and 4 also received daily intramuscular injections of 5 mg/kg of vitamin E and 8 mg/kg of vitamin C, respectively. At the end of three months, the livers were removed for light and electron microscopic examinations. Results: Control rats showed a normal liver tissue structure. Group 2 rats exhibited disorganization of the Remak’s fibers, thickening of the basement membrane together with dilatation of the sinusoids near the centrolobular vein, and lymphocyte infiltration in the portal areas. In vitamin E-treated rats, there was a significant decrease in morphological damage, with disappearance of lymphocyte infiltration in the portal areas. Vitamin C-treated rats manifested the least morphological damage, with a rare infiltration to portal areas and decreased number of infiltration cells. Conclusion: Our findings suggest that the use of antioxidants of different properties may help reduce cisplatin hepatotoxicity, thus contributing to clinical applications

The effect of ellagic acid on the repair process of periodontal defects related to experimental periodontitis in rats

Objective: This study aims to evaluate the effect of ellagic acid (EA) by measuring the levels of alveolar bone resorption and inflammatory and oxidative stress markers in the periodontal tissues and serum on the periodontal repair process related to experimental periodontitis in rats. Methodology: Forty Wistar rats were divided into four study groups as follows: Group 1=healthy control (n=10); Group 2=EA control (15 mg/kg)(n=10); Group 3=periodontitis (n=10); Group 4=periodontitis+EA (15 mg/kg) (n=10). The periodontitis model was established by ligating bilateral mandibular first molars for 14 days. Then, rats were given normal saline or EA for another 14 days by gavage administration. Serum and gingiva myeloperoxidase (MPO) activity, 8-hydroxydeoxyguanosine(8-OHdG), and glutathione (GSH) levels were analyzed by ELISA. İmmunohistochemical analysis was used to detect Interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) immunoreactivities in the periodontal tissues. Alveolar bone loss (ABL) and attachment loss (AL) was evaluated by histomorphometry analysis. Results: ABL and AL were statistically higher in group 3 than in groups 1, 2 and 4 and in group 4 than in groups 1 and 2 (p<0.05). MPO activities in gingival tissue and serum were significantly increased in group 3 compared to groups 1 and 2 (p<0.05). Significantly higher serum GSH levels, lower gingiva, and serum 8-OHdG levels, and MPO activity were observed in group 4 compared to group 3 (p<0.05). Rats with periodontitis (group 3) expressed significantly higher immunoreactivities of IL-6 and TNF-α and lower IL-10 immunoreactivity compared to those other groups (p<0.05). IL-6 and TNF-α immunoreactivities significantly decreased and IL-10 immunoreactivity increased in group 4 after the use of EA compared to group 3 (p<0.001). Conclusions: Our findings showed that EA provides significant improvements on gingival oxidative stress and inflammatory markers and alveolar bone resorption in the repair process associated with experimental periodontitis. Therefore, EA may have a therapeutic potential on periodontitis

Protective effects of curcumin against gamma radiation-induced ileal mucosal damage

The 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 (γ)-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 γ-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

Examining the protective effects of curcumin and vitamin c against gamma radiation-induced ileum goblet cell damage at light and electron microscopic levels

Doktora TeziGastrointestinal 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.The gastrointestinal tract is a very sensitive organ and is important in protecting against the effects of radiation. It is known that the cytotoxic effect of ionized radiation on the intestinal mucosa is related to oxidative stress. Antioxidant substances are claimed to have beneficial effects against radiation damage. In our study, the protective effects of curcumin and vitamin C, whose antioxidant effects are well known, were investigated in rats when different doses of gamma radiation were applied. Light and electron microscopy were employed to examine damage in the goblet cells of the ileum. For this study, 42 Wistar albino male rats, taken from Trakya University Animal Care and Research unit, were divided into seven groups (one control group and six experimental groups). To create radiation damage, 5 Gy of gamma rays were applied to the abdominal area of all rats, except those in the control group. On the fourth day following the application of radiation, the rats in the third, fifth, and seventh groups were given a second application of radiation at the same dosage as the first application. To prevent radiation damage, rats in the fourth and fifth groups were given 100 mg/kg of curcumin dissolved in dimetilsulfoxide intragastrically beginning 10 days prior to the application of radiation until they were sacrificed. Those in the sixth and seventh groups were given 100 mg/kg of vitamin C intraperitoneally during the same period. Ileum biopsy samples were taken under anesthesia from the rats in the first, second, fourth, and sixth groups on the fourth day following the first radiation application and from the rats in the third, fifth, and seventh groups on the fourth day following the second radiation application. The samples were processed so that they could be observed using light and electron microscopy. In this study, it was observed that 5 Gy of gamma radiation applied either once or twice caused damage in the ileum mucosa. Additionally, it resulted in disorganized shape and settlement of the goblet cells. In particular, it caused especially disordered dispersal of the goblet cells, which increased in number due to radiation, in the mucosa. Using electronmicroscopy, extensions in the area between the cells, disorders in the microvilluses, mitochondrial damage and dilatation were observed. This was most distinctive in the rough endoplasmic reticulum cysternas. The preventive effects of curcumin applied prior to radiation doses were seen using both light and electron microscopy. The minimal radioprotective dose that was applied was not found to provide efficient protection from the prooxidant effects of vitamin C. It was concluded that curcumin can strengthen the treatment by protecting the intestinal mucosa during radiotherapy and can be beneficial for clinical usage. Keywords: gamma-radiation, ileum, goblet cell, curcumin, vitamin C, rat

İmmünohistokimyasal boyanmış seminifer tübül hücrelerinin ileri beslemeli yapay sinir ağı yardımıyla sayılması ve tanınması

25th Signal Processing and Communications Applications Conference, SIU 2017 -- 15 May 2017 through 18 May 2017 -- -- 128703In this study, the features of the seminiferous tubule sections were extracted and the presence of the cells and cell stain types detected with the help of the feed forward artificial neural network. By looking at the section view with a small window, 78 features were extracted from the pixels seen by the window and used as an input to the artificial neural network. Artificial neural network outputs are decides presence of the cell and the staining of the cell. The results obtained with the artificial neural network were determined by using the connected component labeling method. The results obtained with the help of the user and the results obtained with the artificial neural network were compared. It has been shown that the proposed ANN model performs cell counting process comparable to the literature (%76 accuracy). © 2017 IEEE

The Effects of the Angiotensin Converting Enzyme Inhibitor Enalapril and the Angiotensin II Type 1 Receptor Blocker Losartan on Fracture Healing in Rats

Purpose: Angiotensin converting enzyme inhibitors (ACEI) and type I angiotensin receptor blockers (ARB) have been shown to exert significant effects on bone tissue via a local renin-angiotensin-aldosterone system (RAS). The aim of our study was to delineate their influences on fracture healing process. Methods: Sixty adult male Wistar Albino rats were divided into three groups. After undergoing surgical femoral fracture and fixation, the ACEI group received 10 mg/kg of Enalapril, the ARB group received 10 mg/kg of Losartan and the Control group did not receive any medication. Fracture healing was evaluated at second and fifth postoperative weeks by the Lane-Sandhu radiological staging system and by histological scoring system of Huoet al. ACE expression in fracture callus was studied by immunohistochemistry. Results: Both ACEI and ARB groups showed less fibrous tissue in the fracture area at the second week, but the histologic score differences were significant only between Control and ARB groups. At the fifth week, however, both radiological and histological scores for the ACEI group were significantly higher than both ARB and Control groups, while the scores for ARB and Control groups were similar. The presence of ACE expression in fracture callus was also observed. Conclusion: ACEIs had significant positive effects on fracture repair. Losartan failed to display these stimulatory effects, which suggests that local RAS in bone tissue exerts its actions via alternative receptors or pathways than the AT1 receptor

The role of central histaminergic system in the analgesic effect of morphine in mice

Amaç: Farelerde morfinin analjezik etkilerine aracılık eden histaminin kaynağının santral histaminerjik nöronlardan salınan histamin mi, yoksa mast hücrelerinin içerdiği histamin mi olduğu araştırıldı. Gereç ve Yöntem: Bu amaçla önce morfinin analjezik etkisi çalışıldı, daha sonra çalışmamızda kullanılan histamin H, ve H2 reseptör blokörlerinin ağrı üzerine ne tür etki yaptıkları ölçüldü. Analjezi ölçümü için hot plate analjezimetre kullanıldı. Bulgular: Dinletinden, feniramin (histamin H1 reseptör blokörleri) ve ranitidinin (H2 reseptör blokörü) analjezik etkilerinin olmadığı istatistiksel olarak gösterildi. Morfin ile histamin antagonistlerinin aralarında etkileşim olup olmadığını anlamak için histamin antagonistlerinin uygulanan tüm dozları, morfin (10 ve 30 mg/kg) ile kombine verilerek hot plate ölçümleri yapıldı. Dimetinden ve feniramin morfinin etkisinde anlamlı bir değişiklik meydana getirmedi, ancak dimetindenin (100 mg/kg) kullanılan dozlarının en yükseğinde morfinin etkisini potansiyalize ettiği görüldü. Ranitidin ise hem i.p. hem de i.c.v. uygulandığında morfinin (10 ve 30 mg/kg, i.p.) analjezik etkisini antagonize etti. Bu sonuçlara göre morfinin analjezik etkisine histamin H2 reseptörleri aracılık etmektedir. Morfinin analjezik etkisinde histaminin kaynağını belirlemek için hem i.p. hem de i.c.v. olarak 48/80 maddesi kullanıldı. Bu şekilde mast hücreleri degranüle edildikten sonra morfin uygulandığında elde edilen sonuçlar mast hücresi sağlam farelerden alman sonuçlar ile karşılaştırıldığında, mast hücreleri degranüle edilmiş farelerde morfinin analjezik etkisinin devam etmesine karşın, istatistiksel olarak azaldığı belirlendi. Sonuç: Çalışmamız morfinin analjezik etkisine histamin H2 reseptörlerinin aracılık ettiğini ve bu etkide nöronal histamine ek olarak mast hücrelerinin de rolü olabileceğini göstermektedir.Purpose: We investigated the source of histamine contributing to the analgesic effect of morphine in mice; whether it is secreted from histaminergic neurons or mast cells. Methods: First, we studied the analgesic effect of morphine, then evaluated the effects H1, and H2 receptor blockers on pain. To measure analgesia, we used hot plate analgesimeter. Results: With these tests we demonstrated that H1 (dinethindene and pheniramine) and H2 receptor blockers (ranitidine) had no statistically significant analgesic effects. In order to determine whether there is an interaction between histamine antagonists and morphine, hot plate measurements were performed, combining morphine (10 and 30 mg/kg) with histamine antagonists, Dimethindene and pheniramine didn't make any significant change in the effect of morphine; however dimethindene (100 mg/kg), with its highest dose, augmented the analgesic effect of morphine. On the other hand, both i.p. and i.c.v. administrations of ranitidine antagonized the analgesic effect of morphine. We concluded that histamine H2 receptors mediate the analgesic effect of morphine. In order to determine the source of histamine in the analgesic effect of morphine, compound 48/80, a selective mast cell degranulator was administered i.p. and i.c.v. After mast cells were degranulated, control measurements were taken and then morphine was applied (10 and 30 mg/kg). When these results were compared with the results obtained from mice which had intact mast cells, the analgesic effect of morphine was found to be attenuated in mice whose mast cells were degranulated. Conclusion: These results show that the analgesic effect of morphine is mediated by histamine H2 receptors; moreover, besides central histaminergic system, mast cells' histamine content might also play role in the analgesic effect of morphine

The Adriamycin Rat/Mouse Model And Its Importance To The Embryology

Adriyamisinin teratojenik etkisi ile oluşturulan sıçan ve fare modelleri; güvenilir, kolaylıkla uygulanabilen ve insanlarda VACTERL birlikteliğinde görülen anomalilere benzer oluşabilen bir dizi konjenital anomalinin embriyolojik ve moleküler biyolojik olarak araştırılmasına olanak veren modellerdir. Adriyamisinin VACTERL birlikteliğinde görülen konjenital anomalileri oluşturma mekanizması henüz tam olarak açıklanamamıştır. Bu modellerle yapılan araştırmalarda özellikle anormal notokord morfolojisi üzerinde durulmuş ve embriyo gelişiminde notokordun rolünün ve öneminin anlaşılmasına ışık tutmuştur. Ayrıca hatalı Sonic hedgehog (Shh) sinyal yolu da üzerinde durulan diğer mekanizmayı oluşturmaktadır. Bu derlemede, adriyamisin sıçan ve fare modelleri ile bu modellerin VACTERL birlikteliğinde görülen konjenital anomaliler üzerine etkisinin, güncel literatür bilgileri ışığında ele alınması amaçlanmıştır.Rat and mouse models induced by the teratogenic effect of adriamycin are reliable and easly reproducible methods of studying the embryology and molecular biology of a range of complex congenital anomalies similar to those seen in humans with VACTERL association. The mechanism by which adriamycin produces the congenital anomalies found in the VACTERL association is not yet clear. Studies with these models have focused on mainly abnormal notochord morphology, shedding more light on the important role of this structure in the developing embryo. Morover, defective Shh signaling pathway is another emphasized mechanism. This review aims to discuss adriamycin rat and mouse models and their impact on congenital anomalies similar to those seen in humans with VACTERL association, in the light of current literature data