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Effect of combining an angiotensin-converting enzyme inhibitor and a vitamin D receptor activator on renal oxidative and nitrosative stress in diabetic rats

Tarek Mohamed Ali, Basem Hassan El Esawy, Elsayed A Elmorsy.

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 specific vitamin D receptor activator paricalcitol, alone or in combination, using a diabetic rat model.

Materials and Methods: Fifty rats were divided into five groups of 10 rats each. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg bw). Group 1 consisting of normal rats was served as control group. Group 2 was treated with vehicle (100 μl propylene glycol ip), group 3 was treated with enalapril (25 mg/l in drinking water), group 4 was treated with paricalcitol (0.8 μg/kg ip, 3 weeks), and group 5 was treated with both drugs. The rats were treated for 3 months. 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 significantly lower blood glucose, malondialdehyde, nitric oxide, levels and significantly 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.

Key words: Enalapril; Paricalcitol; Oxidative and Nitrosative Stress; Diabetic Nephropathy; Rats



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