الفهرس | Only 14 pages are availabe for public view |
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 and 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 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% in comparison to DN untreated group. Ramipril treated animals showed reduction in ATF6 level by 65.5% and reduction in albuminuria by of 50.2% in comparison to DN untreated group. 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 stress-mediated 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. Key words: Diabetic nephropathy; ER stress; Albuminuria; UDCA; Ramipril. |