Dose-dependent effects of meloxicam administration on cyclooxygenase-1 and cyclooxygenase-2 protein expression in intrauterine tissues and fetal tissues of a sheep model of preterm labor.
Meloxicam (MEL), a cyclooxygenase (COX)-2 inhibitor, decreases prostaglandin production and blocks preterm labor in sheep. The objective of this study is to investigate MEL dosage regimens on COX-1, COX-2, and prostaglandin dehydrogenase (PGDH) expression in ovine intrauterine and fetal tissues. Animals in preterm labor received maternal infusions of saline or MEL at maintained high or graded doses (study 1) or acute graded doses (study 2). MEL blocked preterm labor. In study 1, MEL decreased COX-2 expression in the endometrium, myometrium, and amnion but not placenta or fetal tissues. In study 2, COX-2 expression was unchanged. COX-1/PGDH expression was unaffected. While MEL is an effective tocolytic, reductions in COX-2 protein occurred only with maintained MEL exposure. MEL effects are tissue specific and do not affect COX-1 or PGDH expression. Maternal MEL does not affect fetal COX expression in the sheep, possibly contributing to its lack of fetal side effects.
Rac
Valeria E
VE
Research Centre for Women's and Infant's Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Scott
Catherine A
CA
Small
Charlene
C
Adamson
S Lee
SL
Rurak
Dan
D
Challis
John R
JR
Lye
Stephen J
SJ
D000818:Animals; D051545:Cyclooxygenase 1 / Q000096:biosynthesis* / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077239:Meloxicam; D007752:Obstetric Labor, Premature / Q000188:drug therapy* / Q000201:enzymology*; D011247:Pregnancy; D012756:Sheep; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000077239:Meloxicam