Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/61604

TitleCyclooxygenase-2 expression on ifosfamide-induced hemorrhagic cystitis in rats
Author(s)Macedo, Francisco Yuri Bulcao
Baltazar, Fátima
Almeida, Paulo Roberto Carvalho
Távora, Fábio
Ferreira, Francisco Valdeci
Schmitt, Fernando C.
Brito, Gerly Anne Castro
Ribeiro, Ronaldo Albuquerque
KeywordsAnimals
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cystitis
Drug Therapy, Combination
Etoricoxib
Hemorrhage
Ifosfamide
Immunoenzyme Techniques
Indomethacin
Male
Mesna
Pentoxifylline
Protective Agents
Pyridines
Rats
Rats, Wistar
Sulfones
Thalidomide
Hemorrhagic cystitis
TNF-alfa
Myofibroblasts
TNF-alpha
Issue dateJan-2008
PublisherSpringer
JournalJournal of Cancer Research and Clinical Oncology
Abstract(s)Purpose 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.
TypeArticle
URIhttp://hdl.handle.net/1822/61604
DOI10.1007/s00432-007-0237-6
ISSN0171-5216
e-ISSN1432-1335
Peer-Reviewedyes
AccessRestricted access (UMinho)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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