Evaluating the potential of tauroursodeoxycholic acid as add-on therapy in amelioration of streptozotocin-induced diabetic kidney disease

Abstract

The bile acid tauroursodeoxycholic acid (TUDCA) is of natural origin and is used in traditional Chinese medicine for centuries. Earlier its use was limited to biliary disorders but owing to its pleiotropic effects dietary TUDCA supplementation is under clinical trials for diseases including type 1 and 2 diabetic complications.

The current study aims to evaluate the potential and underlying molecular mechanism of the TUDCA as a monotherapy and as an add-on therapy to telmisartan, an angiotensin II type 1 receptor (AT1R) blocker against diabetic kidney disease (DKD). We employed both in-vitro and in-vivo approaches where NRK-52E cells were incubated with high glucose, and DKD was induced in Wistar rats using streptozotocin (55 mg/kg, i.p.). After 4 weeks, animals were administered with TUDCA (250 mg/kg, i.p.), telmisartan (10 mg/kg, p.o.), and their combination for 4 weeks. Plasma was collected for the biochemical estimation and kidneys were used for immunoblotting, PCR, and histopathological analysis. Similarly, for in-vitro experiments, cells were exposed to 1000 μM of TUDCA and 10 μM of telmisartan, and their combination, followed by cell lysate collection and immunoblotting analysis.