Evaluation of the tocolytic effect of a selective cyclooxygenase-2 inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery.
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 F(2alpha)(PGF(2alpha)) and PGE(2) 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.
Sakai
M
M
Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama, Japan.
Tanebe
K
K
Sasaki
Y
Y
Momma
K
K
Yoneda
S
S
Saito
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000068579:Celecoxib; D002821:Chorioamnionitis / Q000150:complications*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004374:Ductus Arteriosus, Patent / Q000473:pathology; D005260:Female; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000188:drug therapy*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D015145:Tocolysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014599:Uterus / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D015237:Dinoprost; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D015232:Dinoprostone