Hematopoietic Effects of Valproic Acid in Mouse / 대한소아혈액종양학회지
Korean Journal of Pediatric Hematology-Oncology
;
: 303-309, 2005.
Artigo
em Coreano
| WPRIM
| ID: wpr-181768
ABSTRACT
PURPOSE:
Valproic acid (VPA) has been used as an anticonvulsant for a long time. Recently, there are many reports on VPA activity with regards to intracellular signal transduction, including differentiation, proliferation, and apoptosis. We experienced several hematologic toxicities during the long-term use of VPA. Therefore, we investigated whether VPA has effects on short-term or long-term hematopoiesis with respect to differing concentrations.METHODS:
We obtained bone marrow mononuclear cells (BMMNC) from a 5 week old female C3H/He strain mouse. The BMMNC were cultured in semi-solid media mixed with VPA according to the concentrations of colony forming unit for granulocyte-monocytes (CFU-GM). The concentrations of VPA were used as follows 0.01 mM, 0.1 mM, 1 mM, and 10 mM (therapeutic level 0.07~1.1 mM). We performed long-term liquid culture under VPA to compare the frequency of long-term culture initiating cells (LTC-IC) according to various VPA levels.RESULTS:
The number of CFU-GM was highest with 1 mM of VPA (45.2+/-13.5), with higher therapeutic level than control (25.7+/-11.9), in 0.01 mM of VPA (26.5+/-12.1) and in 0.1 mM of VPA (26.6+/-12.2). In 10 mM of VPA, a toxic level of VPA, was the lowest at 1.6+/-1.1 (P< 0.01). In long-term culture, the frequency of LTC-IC was increased in 0.1 mM of VPA (67.7+/-16.3%), lower therapeutic level than in control (5.5+/-10.6%). In 1 mM of VPA, the high therapeutic level decreased to 81.6+/-9.3%. With toxic levels of VPA, 10 mM, there was no hematopoiesis.CONCLUSION:
The VPA might enhance short-term hematopoiesis at high therapeutic levels, while preserving LTC-IC in long-term hematopoiesis under low therapeutic concentrations. Therefore, we suggest that VPA to be used within a low therapeutic level to escape from hematopoietic suppression when using VPA as long-term medication for seizure control.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Convulsões
/
Células-Tronco
/
Nações Unidas
/
Medula Óssea
/
Transdução de Sinais
/
Ácido Valproico
/
Apoptose
/
Células Progenitoras de Granulócitos e Macrófagos
/
Hematopoese
Limite:
Animais
/
Feminino
/
Humanos
Idioma:
Coreano
Revista:
Korean Journal of Pediatric Hematology-Oncology
Ano de publicação:
2005
Tipo de documento:
Artigo
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