Oral administration of vitamin C and histidine attenuate cyclophosphamide-induced hemorrhagic cystitis in rats.

Cyclophosphamide (CP), a widely used antineoplastic drug causes hemorrhagic cystitis (HC) mainly via induction of oxidative stress. Both vitamin C and histidine have antioxidant properties. The present study aimed to investigate the effects of oral (p.o.) administration of vitamin C and histidine on the CP-induced HC in rats. The animals were divided into two major groups I and II with four subgroups (a, b, c, and d) in each. Groups I and II were treated with intraperitoneal (i.p.) injections of normal saline and CP (200 mg/kg), respectively, thereafter, normal saline, vitamin C (200 mg/kg), histidine (200 mg/kg) and vitamin C plus histidine were p.o. administered in subgroups a, b, c, and d, respectively, three times (2, 6, and 24 h) after i.p. injections of normal saline and CP. Blood samples were assayed for total antioxidant capacity (TAC) and malondialdehyde (MDA) levels. Histopathological changes of bladder wall were investigated. The decreased TAC and increased MDA levels of plasma and the severity of hemorrhages, congestion, edema, and leukocyte infiltration of bladder induced by CP were recovered with vitamin C and histidine treatments. Combined treatment with vitamin C and histidine showed a potentiation effect. The results indicated that vitamin C and histidine attenuated the CP-induced HC by reducing of free radical-induced toxic effects.