title: Inhibition of epoxy-eicosanoid degradation improves the tocolytic effects of indomethacin in the uterus from pregnant women.
abstract: The incidence of preterm birth is an increasing problem. Indomethacin, a non-specific cyclooxygenase inhibitor, has been largely used as tocolytic in the treatment of preterm labor. The aim of the present study was to assess a putative synergistic tocolytic effect between the inhibition of the production of prostanoids and stabilization of epoxides fatty acids, particularly arachidonate on spontaneous uterine contractile activity. The experimental work was performed on uterine biopsies from consenting women undergoing elective cesarean delivery at term. Isometric tension measurements were performed on fresh human myometrial strips. Contractile activities have been monitored upon individual and combined treatments of indomethacin, DDMS, an inhibitor of hydroxy-eicosanoids production and AUDA, an inhibitor of epoxy-eicosanoids degradation. Interestingly, a significant and consistent synergic effect was observed when indomethacin and AUDA were simultaneously added, raising the possibility of a combined clinical use of cyclooxygenase and sEH inhibitors in attempt to treat preterm labor.
authors.affiliation: Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, CHUS, QC, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Corriveau
authors.forename: Maryse
authors.initials: M
authors.lastname: Berthiaume
authors.forename: Eric
authors.initials: E
authors.lastname: Rousseau
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Pasquier
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000577:Amides / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D002585:Cesarean Section; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004357:Drug Synergism; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn; D007850:Lauric Acids / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
chemical_list: C504897:12-(3-adamantan-1-ylureido)dodecanoic acid; D000577:Amides; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D015777:Eicosanoids; D007850:Lauric Acids; D013450:Sulfones; D015149:Tocolytic Agents; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; C117975:DDMS; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D004851:Epoxide Hydrolases; D000218:Adamantane; D007213:Indomethacin