Role of Diltiazem in Combination with Glimepiride in Diabetic Nephropathy in Experimental-induced NIDDM Model

Abstract

Diabetic nephropathy (DN) is a major cause of end-stage renal disease in the general population. It is estimated that DN will eventually develop in about 40% of all patients with diabetes; therefore, the prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin (STZ) (90 mg/kg) in neonatal rats, and then, these rats were treated with diltiazem (15.0 mg/kg) in combination with glimepiride (0.5 mg/kg) or with pioglitazone (2.5 mg/kg) in combination with glimepiride (0.5 mg/kg). DN markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of diltiazem with glimepiride is more effective in amelioration of DN than pioglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate, and augmented tumor necrosis factor-a signaling during the development of STZ-induced type 2 DN.