Tocolysis due to the COX-2 inhibitor, meloxicam, is not associated with reduced expression of COX-2 and COX-1 protein in fetal kidney, lung, small intestine, adrenal gland, heart, liver, and brain of sheep in preterm labor

Abstract

ASSOCIATED WITH REDUCED EXPRESSION OF COX-2 AND COX-1 PROTEIN IN FETAL KIDNEY, LUNG, SMALL INTESTINE, ADRENAL GLAND, HEART, LIVER, AND BRAIN OF SHEEP IN PRETERM LABOR VALERIJA RAC, STEPHEN LYE, Mount Sinai Hospital Toronto, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada Mount Sinai Hospital Toronto, Ob/Gyn, Toronto, Ontario, Canada OBJECTIVE: Preterm birth occurs in 5%-10 % of all pregnancies and is associated with considerable neonatal mortality andmorbidity. Labor in sheep is caused by increased production of prostaglandins in uterine and placental tissues by inducible COX-2 isoform. Our previous studies have shown that tocolysis with the specific COX-2 inhibitor meloxicam (MEL) blocks COX-2 protein expression in intrauterine tissues while leaving placental COX-2 expression unchanged. Recent studies have shown that the COX-2 isoform is constitutively expressed in many fetal tissues and some fetal side effects of indomethacin are caused by the inhibition of COX protein expression. We wanted to determine whether meloxicam administration induced changes in COX protein expression in different fetal tissues. STUDY DESIGN: On day 127 of gestation, preterm labor was induced in chronically catheterized sheep by maternal administration of RU486. Animals were randomized to receive maternal infusions of saline (n = 12) or MEL (n = 12). Infusion of saline/drug continued until delivery or for 48 hours when the animals were euthanized and tissue samples were collected. Western blot analysis was used to compare COX-1 and COX-2 protein levels in fetal kidney, lung, small intestine, adrenal gland, heart, liver, and brain. RESULTS: (a) MEL administration was not associated with any change in COX-2 protein expression in fetal kidney, lung, small intestine, adrenal gland, heart, liver, and brain in salineand MEL-treated sheep. (b) COX-1 protein expression in these fetal tissues was not significantly different in MEL-treated animals compared to saline-treated animals. CONCLUSION: These studies indicate that meloxicam, at the dose used, did not block COX-1 and COX-2 protein expression in fetal tissues and this might contribute to the absence of fetal complications associated with tocolysis using meloxicam.