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Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna
Morais, M. M; Belarmino-Filho, J. N; Brito, G. A. C; Ribeiro, R. A.
  • Morais, M. M; Universidade Federal do Ceará. Departamentos de Fisiologia e Farmacologia.
  • Belarmino-Filho, J. N; Universidade Federal do Ceará. Departamentos de Fisiologia e Farmacologia.
  • Brito, G. A. C; Universidade Federal do Ceará. Faculdade de Medicina. Departamento de Morfologia.
  • Ribeiro, R. A; Universidade Federal do Ceará. Faculdade de Medicina. Departamentos de Fisiologia e Farmacologia.
Braz. j. med. biol. res ; 32(10): 1211-5, Oct. 1999. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-252270
RESUMO
Chemotherapy with oxazaphosphorines, such as cyclophosphamide (CYP), is often limited by unacceptable urotoxicity. Without uroprotection, hemorrhagic cystitis (HC) becomes dose-limiting. To compare the uroprotective efficacy of classical 2-mercaptoethanesulfonic acid (Mesna) treatment with dexamethasone in CYP-induced HC, male Wistar rats (150-200 g; N = 6 in each group) were treated with saline or Mesna (40 mg/kg, ip) immediately and 4 and 8 h after ip administration of CYP (200 mg/kg). One, 2 or 3 doses of Mesna were replaced with dexamethasone (1 mg/kg, ip). The animals were sacrificed 24 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BWW) and by macroscopic and microscopic analysis. CYP treatment induced a marked increased in BWW 162 percent 0.05, which was significantly inhibited by treatment with 3 doses of Mesna 0.05; 80 percent. The replacement of 1 or 2 doses of Mesna with dexamethasone reduced the increase in BWW by 83.3 and 95 percent, respectively. Macroscopic analysis of the bladder of rats with CYP-induced HC showed severe edema and hemorrhage, confirmed by microscopic analysis, that also showed mucosal erosion, inflammatory cell infiltration and ulcerations. The replacement of 1 or 2 doses of Mesna with dexamethasone inhibited the CYP-induced increase in BWW and almost abolished the macroscopic and microscopic alterations, with no significant difference between the effects of Mesna and dexamethasone, indicating that both drugs were efficient in blocking HC. However, although the replacement of all Mesna doses with dexamethasone reduced the edema, it did not prevent HC, suggesting that Mesna is necessary for the initial uroprotection
Assuntos
Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Dexametasona / Mesna / Substâncias Protetoras / Ciclofosfamida / Cistite / Hemorragia Limite: Animais Idioma: Inglês Revista: Braz. j. med. biol. res Assunto da revista: Biologia / Medicina Ano de publicação: 1999 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Dexametasona / Mesna / Substâncias Protetoras / Ciclofosfamida / Cistite / Hemorragia Limite: Animais Idioma: Inglês Revista: Braz. j. med. biol. res Assunto da revista: Biologia / Medicina Ano de publicação: 1999 Tipo de documento: Artigo