eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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1/2009
vol. 5
 
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abstract:

BASIC RESEARCH
Protective effect of N-acetylcysteine on cyclosporine A-induced changes in lipid hydroperoxide levels and renal dysfunction in rats

Nagaraja Haleagrahara
,
Tan Mun Yee
,
Srikumar Chakravarthi
,
Nagarajah Lee

Arch Med Sci 2009; 5, 1: 16-22
Online publish date: 2009/04/22
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Introduction: One of the major adverse effects of long-term cyclosporine is chronic nephrotoxicity. Renal damage due to cyclosporine treatment is an important clinical challenge. N-acetylcysteine (NAC) is a potent antioxidant and has been shown to reduce free radical injury. The aim of this study was to investigate the possible protective role of NAC treatment on cyclosporine-induced renal damage using biochemical and histopathological parameters.
Material and methods: Adult male albino rats were randomly assigned to control (saline treated), cyclosporine (20 mg/kg/day), NAC alone (20 mg/kg/day) and cyclosporine + NAC (20 mg/kg/day) groups. Rats were sacrificed at the end of the experiment and serum was analyzed for urea, uric acid, creatinine and blood urea nitrogen (BUN). Total antioxidant level and lipid hydroperoxides were also estimated. Histopathological changes in the kidneys were assessed semiquantitatively.
Results: Cyclosporine treatment produced a significant increase in serum creatinine, urea, uric acid and BUN, indicating a marked renal injury. Treatment with N-acetylcysteine significantly reduced these changes. Total antioxidant level decreased significantly both in serum and kidneys after cyclosporine. Administration of NAC significantly prevented these changes. Lipid hydroperoxide level increased significantly with cyclosporine and the changes were reduced when supplemented with NAC. Cyclosporine treatment produced severe glomerular atrophy, blood vessel thickening and moderate tubular necrosis. N-acetylcysteine significantly prevented these histopathological changes in the kidneys.
Conclusions: Depletion of antioxidants and increased lipid hydroperoxides play an important role in cyclosporine-induced renal damage. N-acetylcysteine supplementation significantly reduced cyclosporine induced structural and functional impairment of the kidneys. Concurrent use of antioxidant N-acetylcysteine may be of therapeutic value to minimize cyclosporine-induced nephrotoxicity.
keywords:

cyclosporine, N-acetylcysteine, nephrotoxicity, antioxidants, lipid hydroperoxides Introduction

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