Gülistan Sanem SARIBAŞ, Halime TOZAK YILDIZ, Ozkan GORGULU

Elajik Asit, Diyabetik Böbrek Hasarında TGFβ1/Smad Kaynaklı Böbrek Fibrozisini İnhibe Eder

Amaç: Diabetes mellitus (DM) patogenezinde meydana gelen hiperglisemi nedeniyle serbest radikal oluşumu artar ve bunun sonucunda da oksidatif stres meydana gelir. Hiperglisemi aracılı oksidatif stres, diyabetik nefropatinin patogenezinde önemli bir rol oynar. Elajik asit (EA)’in antihiperglisemik, antioksidatif, antiapoptotik ve antiinflamatuar etkileri birçok çalışma ile gösterilmiştir. Bu çalışmada, streptozotosin ile indüklenen diyabetik nefropatili ratlarda EA’nın TGFβ1/Smad sinyalizasyonu üzerine antifibrotik etkisinin gösterilmesi amaçlandı. Gereç ve Yöntemler: Bu çalışmada, ağırlığı 200-250 g arasında olan toplam 24 adet erkek Sprague Dawley cinsi sıçan kullanıldı. Hayvanlar kontrol, EA, DM ve DM+EA grupları olmak üzere dört gruba ayrıldı. Böbrek dokuları histolojik ve immünohistokimyasal prosedürler için kullanıldı. Masson trikrom boyaması ile böbrek dokularındaki kollajen yoğunluğu ortaya koyulurken, fibrotik belirteçler olan TGFβ1, p-Smad3 ve αSMA'nın ekspresyon seviyeleri ise immünositokimyasal yöntem ile belirlendi. Bulgular: DM grubunun böbrek dokusundaki kollajen yoğunluğunun intertübüler alanda önemli bir ölçüde arttığı gösterilirken, EA ile tedavi edilen DM grubunda ise kollajen yoğunluğunun istatistiksel olarak anlamlı bir derecede azaldığı gösterildi. Tüm grupların böbrek doku kesitlerinde TGFβ1, p-Smad3 ve αSMA immünopozitifliği değerlendirildiğinde ise en yüksek boyanma yoğunluğu DM grubunda olurken, tedavi grubunda boyanma yoğunluğu ise kontrol grubuna yakındı. αSMA, TGFβ1 ve p-Smad3 protein ekspresyonunun EA tedavisi ile aşağı regüle edildiği gözlendi. Sonuç: Elajik asit, diyabetik nefropatide profibrotik parametreleri normal seviyelere döndürerek fibrozu azaltmıştır.

Anahtar Kelimeler:

Diabetes mellitus, elajik asit, fibrozis, böbrek, TGFβ/Smad

Ellagic Acid Inhibits TGFβ1/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 TGFβ1/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 TGFβ1, p-Smad3, and αSMA 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 TGFβ1, p-Smad3, and αSMA 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 αSMA, TGFβ1, 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.

Keywords:

Diabetes mellitus, ellagic acid, fibrosis, kidney, TGFβ/Smad,

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