Safron J, Rice D, Gordon D, Leaf C, White R
Corporate Research and Technical Services, Baxter Healthcare Corporation, Round Lake, Illinois 60073, USA.
J Urol. 1997 May;157(5):1946-50.
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) 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 once 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.
出血性膀胱炎是环磷酰胺（CP）治疗癌症时限制治疗的副作用。本研究旨在探讨L-2-氧代噻唑烷-4-羧酸（OTZ；半胱胺）对CP诱导的大鼠膀胱炎的潜在保护作用。
36只大鼠分为6组：第1组——未治疗对照组；第2组——单独使用OTZ（100毫克/千克，口服）；第3组——单独使用CP（68毫克/千克，静脉注射）；第4组——CP + OTZ（68毫克/千克，静脉注射 + 100毫克/千克，口服）；第5组——CP + OTZ（68毫克/千克，静脉注射 + 1.0克/千克，静脉注射）；第6组——CP + OTZ（68毫克/千克，静脉注射 + 1.0克/千克，腹腔注射）。在CP给药前一天和给药当天，第2组和第4组每天给予OTZ一次。在CP给药前一天、给药当天和给药后一天，第5组和第6组每天给予OTZ两次。在CP给药当天，在给予OTZ前30分钟给予CP。在CP给药两天后采集血液和膀胱样本进行评估。
在所有接受CP的组中均发现血细胞参数预期的降低，各CP治疗组之间未观察到差异。在所有CP治疗组的膀胱中均发现组织学变化（膀胱炎）。发现CP + OTZ组的病变比单独接受CP的组轻，较高剂量的OTZ导致病变发生率和严重程度显著（p < 0.05）降低。
在本研究条件下，L-2-氧代噻唑烷-4-羧酸可降低CP诱导的大鼠膀胱病变的发生率和严重程度。需要进一步研究以探讨最佳给药方案、作用机制以及对环磷酰胺抗肿瘤活性的干扰和长期副作用的预防。
