Comparison of uroprotective efficacy of mesna and amifostine in cyclophosphamide- induced hemorrhagic cystitis in rats

Abstract

Background:Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray′s criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group ( P P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II ( P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.