Effect of combining an angiotensin-converting enzyme inhibitor and a vitamin D receptor activator on renal oxidative and nitrosative stress in diabetic rats
Journal Title: National Journal of Physiology, Pharmacy and Pharmacology - Year 2015, Vol 5, Issue 3
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: 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 treatment group (CG)treated with both enalapril and paricalcitol with the same doses described above. A group of 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 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: Cotreatment with both drugs exerts a synergistic protective effect against diabetic nephropathy by decreasing oxidative and nitrosative stress.
Authors and Affiliations
Tarek Mohamed Ali, Basem Hassan El Esawy, Elsayed A Elmorsy
Keywords
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- EP ID EP101613
- DOI 10.5455/njppp.2015.5.1401201522
- Views 77
- Downloads 0
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