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

Abstract

INTRODUCTION: Diabetic cardiomyopathy is a consequenceof free fatty acid oxidation, dysfunction in mitochondria,oxidative stress and diffuse myocardial fibrosis. We aimed toinvestigate the anti-inflammatory and anti-fibrotic effect ofursodeoxycholic acid in streptozocin-induced diabetic ratmodel.METHODS: Male Sprague Dawley albino mature rats weredivided into 3 groups: Group 1 (n=10) control group; group 2(n=10) diabetic rats group; group 3 (n=10): diabetic ratstreated with ursodeoxycholic acid group. Diabetes mellitusmodel was established after injection of intraperitonealstreptozocin. Histopathological and biochemical examinationswere done after 4 weeks from heart tissues. Immunoexpressionlevels of fibronectin and TGF-? were obtained.Malondialdehyde levels were used to determine lipidperoxidation and pentraxin-3 levels were used to determineinflammation. Myocardial damage was also determined withtroponin-T and pro-BNP levels.RESULTS: Cardiac muscle cell thickness (hypertrophy), TGF? levels, fibronectin immunoexpression malondialdehyde,pentraxin-3, troponin-T and pro-BNP levels were increasedsignificantly in groups 2 and 3 when compared to controlgroup. Administration of ursodeoxycholic acid significantlyreduced inflammation and fibrosis in group 3 compared togroup 2.DISCUSSION AND CONCLUSION: In this experimentalstudy, we demonstrated the anti-inflammatory and anti-fibroticeffects of UDCA on diabetic rats and it can be a good drugcandidate 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-? immunekspresyonu, TGF-?, malondialdehid, pentraxin-3, pro-BNP ve troponin-T düzeyleri ölçüldü. BULGULAR: Fibronektin immunekspresyonu, TGF-?, 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.