Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis.
OBJECTIVE
Hemorrhagic cystitis (HC) is a limiting side-effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS-induced HC.


METHODS
Male Wistar rats (150-200 g; 6 rats per group) were treated with saline or mesna 5 min (i.p.) before and 2 and 6 h after (v.o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis.


RESULTS
The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84.79% and 89.13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically.


CONCLUSIONS
Dexamethasone in combination with mesna was efficient in blocking IFS-induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC.
Vieira
Milena Morais
MM
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
Brito
Gerly Anne Catro
GA
Belarmino-Filho
José Nelson
JN
Macedo
Francisco Yuri Bulcão Macedo
FY
Nery
Erik Aquino
EA
Cunha
Fernando Queiroz
FQ
Ribeiro
Ronaldo Albuquerque
RA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D007069:Ifosfamide / Q000009:adverse effects*; D008297:Male; D015080:Mesna / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000008:administration & dosage; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology
D000893:Anti-Inflammatory Agents; D020011:Protective Agents; D012965:Sodium Chloride; D003907:Dexamethasone; D015080:Mesna; D007069:Ifosfamide