Effect of the antenatal administration of celecoxib during the second and third trimesters of pregnancy on prostaglandin, cytokine, and nitric oxide levels in rabbits.

Abstract

The purpose of this study was to examine the effects of celecoxib on prostaglandin, cytokine, and nitric oxide synthesis in the pregnant rabbit. Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13 to 28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Blood and tissue were assayed for prostaglandin, cytokine, and nitric oxide oxidation products. Preterm delivery occurred in 4 of 11 controls, 0 of 9 in celecoxib-A, and 0 of 8 in celecoxib-B. Plasma prostaglandin F(2alpha) was reduced in both treated groups at 20 days and at delivery in celecoxib-B. Plasma thromboxane B(2) was suppressed in celecoxib-B at 20 days and delivery. Cervical prostaglandin E(2) was increased; uterine and cervical plasma thromboxane B(2) declined in celecoxib-B. Celecoxib administration suppressed plasma nitric oxide oxidation products at delivery and cervical nitric oxide oxidation products in celecoxib-B. Uterine and cervical interleukin-1beta and interleukin-6 were decreased, and uterine tumor necrosis factor-alpha increased in celecoxib-B. Further studies are required to evaluate the therapeutic benefits of cyclo-oxygenase-2 inhibitors in the setting of preterm parturition.