الفهرس 
Aim of The WorkOnly 14 pages are availabe for public view
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Abstract
Diabetes mellitus is a complex metabolic disorder with distinct subtypes associated with multiple underlying causes of its associated hyperglycemia. The most debilitating complication of T2DM and the primary, leading cause of ESRD is DKD.
Although metformin is considered the drug of choice in treatment of type 2 diabetes, it was not proved that it completely reverse the renal damage caused by diabetic nephropathy and prolonging the survival of diabetic mice (242).
ETs are a family of peptides that function as pro-fibrotic growth factors and powerful vasoconstrictors. ET-1 plays an important role in renal and cardiovascular pathophysiology. Hyperglycemia is a significant promoter of ET-1 overexpression; laboratory studies in T1DM and T2DM have reported a link between rates of ET-1 and progressive glomerular damage, extracellular matrix deposition, and renal fibrosis.
The aim of the present investigation was to study the possible protective effect of bosentan (a non-selective ETA/ETB receptor antagonist) on renal impairment in type 2 diabetic rats and the underlying mechanisms involved. To achieve this goal, fifty adult white male albino rats were used. They were divided equally into 5 groups: Non-Diabetic; Diabetic non-treated; Diabetic Bosentan-treated group; Diabetic Metformin-treated; Diabetic combined Bosentan and Metformin-treated.
At the end of the experimental period (4 weeks), 24hrs urine samples were collected for rats by using metabolic cages to measure urine volumes (ml/min), urinary albumin (mg/24h), urinary NAG (U/gm UCr) and creatinine concentrations (mg/ml). UACR was calculated.
In the next day, overnight fasted animals were anaesthetized using thiopental sodium (50 mg/kg, i.p.), and each rat was placed on a suitable rodent surgical table. The skin on the ventral aspect of abdomen was opened to expose renal artery for measurement of RBFV and RVR using Doppler technique. After that, direct cannulation of abdominal aorta was done.
Blood samples were used for measuring of fasting serum glucose, HBA1c, fasting serum insulin; complete lipid profile: total cholesterol, triglycerides, high density lipoprotein; renal function tests: serum creatinine, serum Cystatin C, serum BUN, parameters of oxidative stress: serum MDA, serum TAC and serum TNFα. Insulin resistance, low density lipoprotein and creatinine clearance were calculated.