Document Type : Original Article
Authors
1
physiology department, faculty of medicine, Menoufia university
2
physiology departement, faculty of medicine, menoufia university
3
physiology department, faculty of medicine, KFS university, Egypt
4
physiology departement, menoufia faculty of medicine
Abstract
Background: Diabetic nephropathy (DN) is characterized by persistent albuminuria and progressive decline in glomerular filtration rate (GFR). Bosentan is a non-peptide mixed antagonist of ET-1. Aim: To investigate the possible protective role of bosentan on renal impairment in T2DM rats and the mechanisms concerned. Materials: Fifty rats were randomly divided into five equal groups; Non-Diabetic (ND), Diabetic non-treated (DN), Diabetic Bosentan-treated (D-Bos.), Diabetic Metformin-treated (D-Met.), Diabetic combined Bosentan and Metformin-treated groups (D-Bos& Met.). T2DM was induced by Streptozotocin (STZ) (35mg/kg) and high fat diet (HFD) for 3 weeks. Both Bosentan and metformin were given orally for 4 weeks. At the end of the experiment, 24hrs urine samples were collected to measure urine (volume, albumin, NAG and creatinine), renal blood flow velocity (RBFV) and peripheral renal resistance (RVR) were measured using Doppler technique. Blood was collected directly from abdominal aorta to estimate fasting serum glucose, glycosylated hemoglobin (HBA1c), serum insulin, complete lipid profile, renal function tests and parameters of oxidative stress: malondialdehyde (MDA), total antioxidant capacity (TAC) and tumor necrosis factor-α (TNFα). Insulin resistance, serum LDL-cholesterol, urinary albumin creatinine ratio (UACR) and creatinine clearance (CC) were calculated. Results: Serum cysteine c, BUN, urinary albumin and UACR were significantly lowered in both D-Bos. & D-Met when compared to the corresponding values in DN while urinary volume, urinary creatinine, CC and RBFV were significantly elevated but serum creatinine, NAG & RVR were significantly lowered in D-Bos. only. Conclusion: Bosentan and metformin treatment both have a renoprotective effect. Combined treatment showed better results.
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