Anti-Inflammatory and Anti-Fibrotic Effects of Ursodeoxycholic Acid in Streptozocin-Induced Diabetic Rats

Abstract

INTRODUCTION: Diabetic cardiomyopathy is a consequence of free fatty acid oxidation, dysfunction in mitochondria, oxidative stress and diffuse myocardial fibrosis. We aimed to investigate the anti-inflammatory and anti-fibrotic effect of ursodeoxycholic acid in streptozocin-induced diabetic rat model. METHODS: Male Sprague Dawley albino mature rats were divided into 3 groups: Group 1 (n=10) control group; group 2 (n=10) diabetic rats group; group 3 (n=10): diabetic rats treated with ursodeoxycholic acid group. Diabetes mellitus model was established after injection of intraperitoneal streptozocin. Histopathological and biochemical examinations were done after 4 weeks from heart tissues. Immunoexpression levels of fibronectin and TGF-β were obtained. Malondialdehyde levels were used to determine lipid peroxidation and pentraxin-3 levels were used to determine inflammation. Myocardial damage was also determined with troponin-T and pro-BNP levels. RESULTS: Cardiac muscle cell thickness (hypertrophy), TGFβ levels, fibronectin immunoexpression malondialdehyde, pentraxin-3, troponin-T and pro-BNP levels were increased significantly in groups 2 and 3 when compared to control group. Administration of ursodeoxycholic acid significantly reduced inflammation and fibrosis in group 3 compared to group 2. DISCUSSION AND CONCLUSION: In this experimental study, we demonstrated the anti-inflammatory and anti-fibrotic effects of UDCA on diabetic rats and it can be a good drug candidate for DM patients

GİRİŞ ve AMAÇ: Diabetik kardiyomyopati, serbest yağ aside oksidasyonu, mitokondrial disfonksiyon, oksidatif stress ve diffuz miyokardiyal fibrozise seconder olarak gelişmektedir. Bu deneysel çalışmada, ursodeoksikolik asidin streptozocin ile tetiklenmiş diabetik fare modelinde anti-inflamatuar ve antifibrotik etkilerini araştırmayı hedefledik. YÖNTEM ve GEREÇLER: Sprague Dawley albino 30 erişkin fare 3 gruba ayrıldı: Grup-1: kontrol grubu (n=10); Grup-2 (n=10) diabetik fare grubu; Grup-3 (n=10) ursodeoksikolik asit verilen diabetic fare grubu. Histopatolojik ve biyokimyasal değerlendirmeler 4 hafta sonra kalp dokusundan yapıldı. Fibronektin ve TGF-β immunekspresyonu, TGF-β, malondialdehid, pentraxin-3, pro-BNP ve troponin-T düzeyleri ölçüldü. BULGULAR: Fibronektin immunekspresyonu, TGF-β, pentraxin-3, troponin-t, pro-BNP ve malondialdehid düzeyleri diabetik farelerde control grubuna göre anlamlı olarak artmış saptandı. Ursodeoksikolik asidin inflamasyon belirteçlerini ve fibroz düzeyini anlamlı olarak azalttığı izlendi TARTIŞMA ve SONUÇ: Bu deneysel çalışmada, ursodeoksikolik asidin diabetik farelerde anti-inflammatuar ve anti-fibrotik etkilerini gösterdik. Diabetik hastalarda ursodeoksikolik asidin ilaç olarak kullanımı klinik olarak fayda gösterebilir