Abstract
Background: Diabetic nephropathy (DN) is a progressive and irreversible renal disease. Experimental researches have established the role of oxidative stress as a central factor in pathogenesis, onset, and advancement of DN. Aims and Objectives: To investigate the effect of the combined treatment with angiotensin-converting enzyme inhibitor, enalapril, and the speciï¬c vitamin D receptor activator paricalcitol, alone or in combination, using a diabetic rat model. Materials and Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg bw). The diabetic (D) rats were treated for 3 months as follows: diabetic control (DC) treated with vehicle (100 ml propylene glycol ip), enalapril treated group (EG; 25 mg/l in drinking water), paricalcitol treated group (PG; 0.8 mg/kg ip, 3 week), or combined treatmentgroup(CG)treatedwithbothenalapril andparicalcitol withthesamedosesdescribedabove.Agroupof normal rats was served as control (N). Biochemical analysis was performed using an automatic biochemistry analyzer. Evaluation of oxidant/antioxidant balance and immunohistochemical localization of 3-nitrotyrosine (3-NT) in the kidney tissue was performed. Results: Combined treatment with both drugs was associated with signiï¬cantly lower blood glucose, malondialdehyde, nitric oxide, levels and signiï¬cantly higher levels of the antioxidant parameters more than those observed for monotherapy. Co-treatment led to additional improvement with negligible interstitial damage with no glomerular or tubular injury detected and strongly decreased 3-NT expression induced by diabetes. Conclusion: Co- treatment with both drugs exerts a synergistic protective effect against diabetic nephropathy by decreasing oxidative and nitrosative stress.