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 reninangiotensin system, and thus suppression of TGF-β1, TNF-α.

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

“…Therefore, results from experimental studies indicate that inhibition of Ang II receptor activity is associated with beneficial renal effects, suggesting that modulation of this cytokine may have a real clinical application for the treatment of DN. 8,9…”

The effect of age and a high-fat, high-carbohydrate diet on the development of arterial hypertension and kidney disease in the experiment

“…Пролиферацию мезангиальных клеток и увеличение синтеза внеклеточного матрикса стимулируют α-SMA и TGF-β1, в результате чего оба фактора были идентифицированы как ключевые медиаторы клубочковой и тубулоинтерстициальной патологии при хронических заболеваниях почек [15]. Возрастание концентрации TGF-β1 наблюдают при нефропатии, обусловленной индуцированным сахарным диабетом у крыс [16]. Однако в нашем исследовании возрастание концентрации TGF-β1 в сыворотке крови крыс происходило у всех 450-дневных крыс независимо от диеты.…”

The Blocking on the Cathepsin B and Fibronectin Accumulation in Kidney Glomeruli of Diabetic Rats

“…Similarly to the fibronectin excretion in the urine per mg creatinine, it has slightly decreased in the groups treated diabetic rats compared to untreated diabetic rats, while the concentration of FN in plasma of rats in all groups examined were in similar extent. Rao et al [ 23 ] giving the rats streptozotocin diabetes ACEi and AT1 blocker received separately and together decrease the concentration of FN in the plasma.…”

“…In other groups of diabetic rats receiving treatment, a decreasing trend of albuminuria has been shown in relation to untreated diabetic rats. Rao et al [ 23 ] demonstrated reduction in daily urinary albumin excretion in treated diabetic rats compared to untreated diabetic rats.…”