Muscimol delays lipopolysaccharide-induced preterm delivery in mice: role of GABA(A) receptors and nitric oxide.
J Matern Fetal Neonatal Med
; 26(1): 36-43, 2013 Jan.
Article
en En
| MEDLINE
| ID: mdl-22913283
ABSTRACT
OBJECTIVES:
Immunologic processes are involved in preterm delivery (PTD). Considering the anti-inflammatory properties of muscimol (GABA(A) agonist), the effect of this drug was evaluated in lipopolysaccharide-induced PTD in mice.METHODS:
PTD was induced by two intraperitoneal injections of lipopolysaccharide (35 µg/kg; n = 11), on gestational day 15 (d15). Muscimol was administered twice on d14 and twice on d15 (1 h prior to each lipopolysaccharide injection; 0.05, 0.1, 0.2 mg/kg; intraperitoneally; n = 8-12). To assess the involved mechanisms, either bicuculline (GABA(A) antagonist; 0.1 and 1 µg/kg; intraperitoneally; n = 6-7) or N(ω)-nitro-l-arginine methyl ester (l-NAME; non-selective inhibitor of nitric oxide (NO) synthase enzymes; 2 mg/kg; intraperitoneally; n = 6) were administered 1 h before each muscimol administration on d14 and the first dose of muscimol on d15. Maternal plasma and amniotic fluid nitrite + nitrate levels, placental histopathologies and uterine contractions were assessed.RESULTS:
Muscimol (0.1 mg/kg) significantly decreased lipopolysaccharide-induced PTD rates from 100 to 50% and delayed delivery time from d16 to d18. Muscimol moderately increased maternal plasma and amniotic fluid nitrite + nitrate concentrations and decreased lipopolysaccharide-induced placental inflammation and surge in nitrite + nitrate levels. Contrary to bicuculline, l-NAME reversed the beneficial effects of muscimol. Muscimol did not affect myometrial contractions.CONCLUSIONS:
Muscimol inhibits lipopolysaccharide-induced PTD through modulating NO release.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de GABA-A
/
Nacimiento Prematuro
/
Agonistas de Receptores de GABA-A
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Muscimol
/
Óxido Nítrico
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
J Matern Fetal Neonatal Med
Asunto de la revista:
OBSTETRICIA
/
PERINATOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Irán