Dual therapy versus monotherapy of trandolapril and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats

Abstract

Objective: To investigate the combination of telmisartan with trandolapril therapy versus monotherapy of trandolapril and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. Material and methods: Neonatal rats (2 days old) were used for inducing type 2 diabetes mellitus. Streptozotocin at a dose of 90 mg/kg, in freshly prepared citrate buffer (0.1M, pH 4.5), was injected intraperitoneally. There were five groups: (1) normal control, (2) diabetic control, (3) diabetic treated with telmisartan, (4) diabetic treated with trandolapril and (5) diabetic treated with telmisartan and trandolapril. Albumin excretion rate, total protein excretion rate, plasma fibronectin, transforming growth factor beta 1(TGF-β1), tumour necrosis factor-α (TNF-α) concentration and renal structural changes were measured. Results: Albumin excretion rate, total protein excretion rate, plasma fibronectin, TGF-β1, TNF-α concentration and renal structural changes increased significantly in untreated diabetic rats compared with normal control rats. Administration of telmisartan, trandolapril, or both decreased these changes. Conclusions: Addition of the telmisartan to trandolapril was more effective in reducing renal structural changes and improvement of renal function than monotherapy with either drug, possibly due to dual inhibitory effect on the renin— angiotensin system, and thus suppression of TGF-β1, TNF-α.