Anti-implantation effects of indomethacin and celecoxib in rats.
Pregnant Wistar rats were used to investigate the anti-implantation effect of cyclooxygenase (COX) inhibitors, indomethacin (nonselective COX-1/COX-2 inhibitor) and celecoxib (specific COX-2 inhibitor). Indomethacin at doses of 2.5 and 5 mg/kg/day and celecoxib at doses of 40, 80, and 160 mg/kg/day were orally administered once daily to each group (n = 8) on Days 3-5 of pregnancy (Day 1 = sperm detection). Indomethacin and celecoxib at anti-implantation dosages were further investigated for the effects on changes in endometrial vascular permeability in pregnant rats and uterine decidualization in pseudopregnant rats. The results demonstrated that indomethacin at a dose of 5 mg/kg/day as well as celecoxib at doses of 80 and 160 mg/kg/day could significantly reduce the proportion of pregnant rats. At the anti-implantation dosages, they exhibited no significant effect on proportion of rats with blue dye sites in the endometrial vascular permeability study, but they could significantly reduce the uterine decidualization. From these findings, the anti-implantation effect of the two COX inhibitors may principally be from decidualization defects, and COX inhibitors should, therefore, be used with caution in childbearing age women. On the other hand, specific COX-2 inhibitors with their good gastric safety profile may have a potential role in nonhormonal postcoital contraception.
Sookvanichsilp
Nongluck
N
Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. pynsw@mahidol.ca.th
Pulbutr
Pawitra
P
D000818:Animals; D000068579:Celecoxib; D003267:Contraception; D003281:Contraceptives, Postcoital / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003656:Decidua / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D011247:Pregnancy; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*
D003281:Contraceptives, Postcoital; D016861:Cyclooxygenase Inhibitors; D006727:Hormone Antagonists; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D007213:Indomethacin