title: Cyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats.
abstract: OBJECTIVE
  Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with ifosfamide (IFS). In this study, we investigated the participation of cyclooxygenase-2 (COX-2) upon ifosfamide-induced HC.
  
  
  METHODS
  Male Wistar rats (150-200 g; six rats per group) were treated with saline, IFS (400 mg/kg, i.p.) and analyzed by changes in bladder wet weight, macroscopic and microscopic parameters, and COX-2 expression. In other groups etoricoxib (selective COX-2 inhibitor), indomethacin (non-selective COX inhibitor), thalidomide (selective TNF-alpha inhibitor), pentoxifyllin (non-selective TNF-alpha inhibitor) were added 1 h before IFS administration. The classical protocol using three doses of Mesna was also evaluated and compared with two extra doses of etoricoxib or indomethacin.
  
  
  RESULTS
  COX-2 was expressed significantly 24 h after IFS administration mainly in myofibroblasts and mast cells evaluated by immunohistochemistry. Treatment 1 h before IFS injection with etoricoxib, indomethacin, thalidomide, and pentoxifylline reduced COX-2 expression and some macroscopic and microscopic parameters in IFS-induced HC. Moreover, addition of etoricoxib or indomethacin with the last two doses of Mesna was more efficient than three doses of Mesna alone when evaluated microscopically.
  
  
  CONCLUSIONS
  COX-2 participates in the pathogenesis of IFS-induced HC and the treatment with COX and TNF-alpha inhibitors reduced COX-2 expression. The addition of COX-inhibitors to the last two doses of Mesna represents a new therapeutic strategy of preventing HC.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Coronel Nunes de Melo, 1315, Rofolfo Teofilo, 60430-270, Fortaleza, CE, Brazil. yuribulcao@gmail.com
authors.forename: Francisco Yuri Bulcao
authors.initials: FY
authors.lastname: Macedo
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
authors.forename: Paulo Roberto Carvalho
authors.initials: PR
authors.lastname: Almeida
authors.forename: Fábio
authors.initials: F
authors.lastname: Távora
authors.forename: Francisco Valdeci
authors.initials: FV
authors.lastname: Ferreira
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
authors.forename: Gerly Anne Castro
authors.initials: GA
authors.lastname: Brito
authors.forename: Ronaldo Albuquerque
authors.initials: RA
authors.lastname: Ribeiro
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003556:Cystitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D004359:Drug Therapy, Combination; D000077613:Etoricoxib; D006470:Hemorrhage / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D007069:Ifosfamide / Q000009:adverse effects*; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D015080:Mesna / Q000627:therapeutic use; D010431:Pentoxifylline / Q000627:therapeutic use; D020011:Protective Agents / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000627:therapeutic use; D013792:Thalidomide / Q000627:therapeutic use
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D020011:Protective Agents; D011725:Pyridines; D013450:Sulfones; D013792:Thalidomide; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015080:Mesna; D010431:Pentoxifylline; D007069:Ifosfamide; D000077613:Etoricoxib; D007213:Indomethacin