Ellagic Acid Inhibits TGF?1/Smad-Induced Renal Fibrosis in Diabetic Kidney Injury

Aim: Free radical formation increases due to hyperglycemia occurring in the pathogenesis of diabetes mellitus (DM), and as a result, oxidative stress occurs. Hyperglycemia-mediated oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The antihyperglycemic, antioxidative, anti-apoptotic, and anti-inflammatory effects of ellagic acid (EA) have been demonstrated by many studies. In this study, it was aimed to demonstrate the antifibrotic effect of EA on TGF?1/Smad signaling in rats with streptozotocin induced diabetic nephropathy. Material and Methods: A total of 24 male Sprague Dawley rats, weighing 200-250 g, were used in this study. The animals were divided into four groups as control, EA, DM, and DM+EA. The kidney tissues were used for histological and immunohistochemical procedures. While the collagen density in kidney tissues was revealed by Masson's trichrome staining, the expression levels of fibrotic markers TGF?1, p-Smad3, and ?SMA were determined by the immunocytochemical method. Results: It was shown that the collagen density in the renal tissue of the DM group increased significantly in the intertubular area, while the collagen density in the EA-treated DM group was statistically significantly decreased. When TGF?1, p-Smad3, and ?SMA immunopositivity in kidney tissue sections of all groups were evaluated, the highest staining intensity was in the DM group, while the intensity of staining was close to the control group in the treatment group. It was observed that ?SMA, TGF?1, and p-Smad3 protein expression were down-regulated with EA treatment. Conclusion: EA reduced fibrosis in diabetic nephropathy by returning profibrotic parameters to normal levels

MELATONİN VE C VİTAMİNİ’NİN KRONİK ALKOLİK SIÇANLARINAKCİĞER DOKUSUNDAKİ HASAR VE eNOS İMMUNREAKTİVİTESİÜZERİNE ETKİLERİ*

Bu &ccedil;alışmada alkol&uuml;n akciğerde oluşturduğu hasarve endotelyal nitrik oksit sentaz ekspresyonu &uuml;zerinemelatonin ve C vitamininin koruyucu etkilerininbelirlenmesi ama&ccedil;landı.&Ccedil;alışmada 24 adet 200-250 gr ağırlığında Wistar cinsiergin erkek sı&ccedil;an kullanıldı. Sı&ccedil;anlar rasgele olarak d&ouml;rtgruba ayrıldı. Birinci grup kontrol (n:6); ikinci grup deneys&uuml;resince (28 g&uuml;n) sadece alkol i&ccedil;eren sıvı diyet alan(n:6); &uuml;&ccedil;&uuml;nc&uuml; grup deney boyunca alkol i&ccedil;eren sıvı diyetile birlikte 40mg/kg/g&uuml;n intraperitoneal C vitamini alan(n:6); d&ouml;rd&uuml;nc&uuml; grup deney s&uuml;resince alkol i&ccedil;eren sıvıdiyet ile birlikte 4mg/kg/g&uuml;n intraperitoneal melatoninalan sı&ccedil;anlardan (n:6) oluşturuldu.Deney s&uuml;resince sadece alkol alan gruptaki sı&ccedil;anlarınakciğer dokularında alveolar septumda kalınlaşma ve bazıbronşiol epitel h&uuml;crelerinde d&ouml;k&uuml;lme g&ouml;zlendi. Bazıalanlarda alveolar &ouml;dem ve hemoraji tespit edildi.Endotelyal nitrik oksit sentaz immunoreaktivitesinibelirlemek i&ccedil;in yapılan boyamada bronşiol epitelh&uuml;crelerinde (+++), alveolar septumda (++) ve bronşiolve damarların d&uuml;z kaslarında ise (+) boyanma tespitedildi. Alkol t&uuml;keten grupta bronşiol epitelindekiboyanmada &ouml;nemli miktarda azalma g&ouml;zlendi. Melatoninve C vitamini gruplarında ise endotelyal nitrik oksit sentazboyanması kontrol grubuna benzerlik g&ouml;stermekteydi veoluşan morfolojik hasarlar d&uuml;zelmişti.Sonu&ccedil; olarak kronik alkol t&uuml;ketimi akciğer dokusundahasara yol a&ccedil;maktadır. Bu hasar melatonin ve C vitaminiile d&uuml;zelmektedir.The aim of this study was to determine theexpression of endothelial nitric oxide synthase andalterations in the lung caused by alcohol consumptionand the effects of melatonin and vitamin C on thesechanges in rats.Twenty-four adult male Wistar rats weighing 200-250gwere used in this study. Rats were divided into fourgroups. The first group served as control (n:6). Thesecond group was the ethanol treatment for 28 days (n:6).The third group was given ethanol and supplemented with40 mg/kg/day vitamin C (intraperitoneally) (n:6). Thefourth group was given ethanol and supplemented with 4mg/kg/day melatonin (intraperitoneally) (n:6).Light microscopic examinations revealed thickening inalveolar septum and desquamation of some bronchialepithelial cells in the ethanol-fed group. In some fields,alveolar edema and hemorrhage wasobserved. Endothelial nitric oxide synthaseimmunoreactivity was in (+++) bronchial epithelial cells,(++) in alveolar septum and (+) in smooth muscle ofbronchioli and vessels. Expression of endothelial nitricoxide synthase in alcohol group was decreased comparedto control group. In melatonin and vitamin C treatedgroups, endothelial nitric oxide synthaseimmunoreactivity resembled that of control group, andmorphological damage was partly improved.Our finding have led us to conclude that chronic alcoholconsumption results in damage to pulmonary tissue,which can only be resolved with especially melatonin andvitamin C.</div