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Alpha‐tocopherol, beta‐carotene and melatonin administration protects cyclophosphamide‐induced oxidative damage to bladder tissue in rats
Author(s) -
Sadir Serdar,
Deveci Salih,
Korkmaz Ahmet,
Oter Sukru
Publication year - 2006
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1347
Subject(s) - melatonin , mesna , hemorrhagic cystitis , cyclophosphamide , vitamin e , urine , malondialdehyde , medicine , chemistry , pharmacology , tocopherol , endocrinology , oxidative stress , antioxidant , chemotherapy , biochemistry , ifosfamide , etoposide
Abstract Cyclophosphamide (CP) has potential urotoxicity such as hemorrhagic cystitis (HC). 2‐Mercaptoethane sulfonate (mesna) has been widely used as an effective agent against CP‐induced cystitis, but significant HC has still been encountered clinically. In recent studies, mesna was shown to be more effective if combined with antioxidants. The purpose of this study was to evaluate the effects of antioxidants, α ‐tocopherol, β ‐carotene and melatonin on CP‐induced bladder damage in rats, even if used without mesna administration. Male Spraque–Dawley rats weighing 180–210 g were divided into 5 groups. Four groups received a single dose of CP (100 mg/kg) intraperitoneally with the same time intervals. Group 2 received CP only, group 3 received β ‐carotene (40 mg/kg/day), group 4 received α ‐tocopherol (40 mg/kg/day) and group 5 received melatonin (10 mg/kg/day) both before and the day after CP injection. Group 1 served as control. Bladder histopathology, as well as malondialdehyde (MDA) and iNOS levels, and excretion of nitrite‐nitrates (NO x ) in urine were evaluated. CP injection resulted in severe histological changes and macroscopic hematuria. α ‐Tocopherol and melatonin showed meaningful protection against bladder damage. Protection by β ‐carotene was also significant but weaker. MDA levels increased significantly with CP injection and all antioxidants ameliorated this increase in bladder tissue. CP also elevated the NO x level in urine and iNOS activity in bladder. Only melatonin was able to decrease these parameters. In conclusion, there is no doubt that oxidants have a role in the pathogenesis of CP‐cystitis. Antioxidants, especially melatonin and α ‐tocopherol, may help to ameliorate bladder damage induced by CP. Copyright © 2006 John Wiley & Sons, Ltd.