Protective Effect of L-2-Oxothiazolidine-4-Carboxylate Treatment of Cyclophosphamide-Induced Cystitis in Rats

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Abstract
Hemorrhagic cystitis is a therapy-limiting side effect of cyclophosphamide (CP) treatment for cancer. The purpose of this study was to investigate the potential protective effect of L-2-oxothiazolidine-4-carboxylate (OTZ; Procysteine [R]) on CP-induced cystitis in the rat. Thirty-six rats were divided into 6 groups: Group 1-Untreated controls, Group 2-OTZ alone (100 mg./kg., p.o.), Group 3-CP alone (68 mg./kg., i.v.), Group 4-CP + OTZ (68 mg./kg., i.v. + 100 mg./kg., p.o.), Group 5-CP + OTZ (68 mg./kg., i.v. + 1.0 g./kg., i.v.), and Group 6-CP + OTZ (68 mg./kg., i.v. + 1.0 gm./kg., i.p.). OTZ was given a day to groups 2 and 4 on the day prior to and on the day of CP administration. OTZ was given twice a day to groups 5 and 6 on the day prior to, the day of, and the day after CP administration. On the day of CP administration, CP was given 30 minutes prior to OTZ. Blood and bladder samples were taken for evaluation two days after CP administration. Expected depression in blood cell parameters were identified in all groups receiving CP with no differences noted between the CP-treated groups. Histologic changes (cystitis) were identified in the bladders of all CP treated groups. The lesions in the CP + OTZ groups were found to be less severe than the groups that received CP alone, with higher dosages of OTZ resulting in a significant (p <0.05) decrease in lesion incidence and severity. Under the conditions of this study, L-2-oxothiazolidine-4 carboxylate caused a reduction in the incidence and severity of cyclophosphamide-induced lesions in the urinary bladder of rats. Further studies are needed to investigate optimal dosage scheme, mechanism of action, and interference with anti-tumor activity and prevention of long-term side effects of cyclophosphamide.

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