Potential Therapeutic Effects of Ursodeoxycholic Acid in Comparison to Ramipril in a Rat model of Diabetic Nephropathy

Abstract

Abstract Background & Aim Diabetic nephrectomy (DN) is a chronic progressive disorder that complicates long standing diabetes. Albuminuria is a prominent clinical feature of DN. Ursodeoxycholic acid (UDCA) is a physiologic hydrodrophillic bile acid that is therapeutically used in the treatment of primary biliary cirrhosis. It is known to alleviate endoplasmic reticulum (ER) stress in podocytes. In comparison to Ramipril as a standard ACEI therapy of DN, the present study was designed to investigate the effect of UDCA treatment on DN in association with renal biomarkers changes. Method Four groups of male Wister rats (6 per group) were designed; Normal control group, DN untreated group (High fat diet + STZ injection of 45 mg/kg + uninephrectomy), DN/Ramipril group; (1 mg/kg/d orally for 12 weeks) and DN/UDCA group (40 mg/kg/d orally for 12 weeks). Results DN rats treated with UDCA for 12 weeks exhibited significant decrease in ER stress marker, ATF6 with mean percentage value of 73.8% and improvement of podocyte structural deformities that is accompanied by a significant reduction in albuminuria by mean percentage value of 43.8% comparatively to Ramipril that caused reduction in ATF6 level with mean percentage value of 65.5% and reduction in albuminuria by mean percentage value of 50.2%. The remarkable improvement in metabolic profile and the neutral effect on blood pressure in UDCA treated group could explain the renoprotection at histopathological basis rather than the proved hemodynamic effect of ramipril. Conclusion Participation of ER stressmediated apoptosis in the pathophysiology of diabetic nephropathy make the UDCA a potential therapeutic option or add-on therapy due to its anti-apoptotic property apart from classic metabolic and hemodynamic aspects.