Molecular Human Reproduction, Vol. 7, No. 6, 595-602,
June 2001
© 2001 European Society of Human Reproduction and Embryology
Implantation and pregnancy |
Evaluation of the tocolytic effect of a selective cyclooxygenase-2 inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery
1 Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama, 930-0194 and 2 Department of Pediatric Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan
Abstract
The inflammatory process is known to cause preterm delivery. Recently, a cyclooxygenase (COX)-2 inhibitor has been developed as an anti-inflammatory drug with few side-effects. We evaluated the COX-2 inhibitor, Celecoxib, for its tocolytic effects and side-effects on dams and pups using a lipopolysaccharide (LPS)-induced preterm delivery mouse model (preterm delivery rates; 95%). With administration of Celecoxib (50, 10, 1 and 0.3 mg/kg), the preterm labour rate was significantly reduced to 18, 30, 36 and 60% respectively. The prostaglandin F2
(PGF2) and PGE2 concentrations in murine uterine tissue 4 and 10 h after LPS treatment with Celecoxib (10 and 1 mg/kg) were significantly lower than those in the LPS-treated group without Celecoxib. With administration of 10 or 100 mg/kg Celecoxib, the fetal ductus arteriosus was constricted significantly in preterm and near-term rats, although constriction rates in preterm rats were significantly lower than those in near-term rats. Reproductive and renal functions in offspring whose mothers were treated with LPS and Celecoxib were normal. These data demonstrate that Celecoxib could be used as a new therapy for preterm labour. However, careful attention to constriction of the fetal ductus arteriosus should be given.
cyclooxygenase-2/ductus arteriosus/mouse/preterm delivery/prostaglandins
Notes
3 To whom correspondence should be addressed. E-mail: s30saito{at}ms.toyama-mpu.ac.jp
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