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,
alpha-tocopherol,
beta-carotene and
melatonin on CP-induced bladder damage in rats, even if used without
mesna administration. Male Sprague-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
beta-carotene (40 mg/kg/day), group 4 received
alpha-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.
alpha-Tocopherol and
melatonin showed meaningful protection against bladder damage. Protection by
beta-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
alpha-tocopherol, may help to ameliorate bladder damage induced by CP.