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The Influence of N-Acetylcysteine Alone and in Combination with Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Antagonist on Systemic and Tissue Levels in Rats with Experimentally-Induced Chronic Renal Failure

The Influence of N-Acetylcysteine Alone and in Combination with Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Antagonist on Systemic and Tissue Levels in Rats with Experimentally-Induced Chronic Renal Failure

Ahmet Ozer Sehirli1,2, Serkan Sayiner3*, Ayliz Velioglu-Ogunc4, Nedime Serakinci5, Emel Eksioglu-Demiralp6, Berrak Yegen7, Feriha Ercan8 andGoksel Sener2

1Department of Pharmacology, Faculty of Dentistry, Near East University, 99138 Nicosia, Cyprus
2Department of Pharmacology, Faculty of Pharmacy, Marmara University, 34722 Istanbul, Turkey
3Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, Cyprus
4Department of Biochemistry, Vocational School of Health-Related Professions, Marmara University, 34722 Istanbul, Turkey 
5Department of Medical Genetics, Faculty of Medicine, Near East University, 99138 Nicosia, Cyprus 
6Department of Haematology and Immunology, School of Medicine, Marmara University, 34722 Istanbul, Turkey 
7Department of Physiology, School of Medicine, Marmara University, 34722 Istanbul, Turkey
8Department of Histology and Embryology, School of Medicine, Marmara University, 34722 Istanbul, Turkey

*      Corresponding author: serkan.sayiner@neu.edu.tr

ABSTRACT

The protective effects of ACE inhibitor, Captopril, and angiotensin receptor blocker, Valsartan, were evaluated in the treatment of chronic renal failure (CRF) with and without the presence of N-acetylcysteine (NAC). The renal mass of Wistar albino rats was reduced at a rate of 5/6. Captopril, Valsartan and NAC were applied intra-peritoneal alone or in combination. Blood pressure and heart rate were monitored at weekly intervals over a period of six weeks. Serum creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH) activity, cytokines (TNF-α, IL-1β, IL-6) concentrations, urinary volume, creatinine, and both serum and urinary electrolyte levels were measured. In addition, the apoptosis rate of white blood cells was analysed from plasma samples. Tissue samples from the brain, heart, aorta and kidneys were used for analysis of the collagen content besides tissue luminol, lucigenin, malondialdehyde (MDA) and glutathione (GSH) levels. A significant difference was determined between the CRF group and the control group with regard to heart rate, blood pressure, serum creatinine, BUN, LDH, cytokines and urinary electrolyte levels. Furthermore, monocyte and neutrophil apoptosis, tissue luminol, lucigenin, malondialdehyde and collagen levels were found to increase. Tissue glutathione levels were found to decrease indicating oxidative damage. These results indicate that oxidative mechanisms induce tissue damage in CRF, and the angiotensin receptor blocker, Valsartan, improved oxidative tissue damage when used in combination with the ACE inhibitor, Captopril or NAC, yielded better results and could be a novel approach for the treatment of CRF when used in combination with anti-oxidants.
 

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Pakistan Journal of Zoology

August

Vol. 52, Iss. 4, Pages 1225-1630

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