Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats.
BACKGROUND
Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP).


OBJECTIVE
In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna.


METHODS
This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University.


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.


METHODS
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<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.


CONCLUSIONS
This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.
Kanat
Ozkan
O
Uludag University, Faculty of Medicine, Department of Medical Oncology, Gorukle 16059, Bursa, Turkey. ozkanat@uludag.edu.tr
Kurt
E
E
Yalcinkaya
U
U
Evrensel
T
T
Manavoglu
O
O
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D003556:Cystitis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D015080:Mesna / Q000494:pharmacology*; D009153:Mutagens / Q000633:toxicity*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects
D009153:Mutagens; D011837:Radiation-Protective Agents; D003520:Cyclophosphamide; D004999:Amifostine; D015080:Mesna