Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives in pregnant human myometrium.
OBJECTIVE
The aim of this study was to assess the involvement of lipoxygenase (LOX) metabolic pathways in uterine tissues from pregnant women as well as the combined inhibition of LOX and cyclooxygenase (COX) on contractile activity.


METHODS
Uterine biopsies were performed from consenting women undergoing elective caesarean sections at term (n = 24). Western blot analysis and isometric tension measurements were performed in vitro on fresh human myometrial strips. Concentration-response curves to arachidonic acid (AA) 861 and baicalein (5- and 12-LOX inhibitors, respectively) were performed. The combined effects of baicalein and indomethacin were also assessed. Contractile activities were quantified by calculating both amplitude and the area under the curve over 20 minute periods.


RESULTS
5- and 12-LOX were present in all tested tissues. Addition of AA861 or baicalein resulted in tocolytic effects (P < .05). Finally, the combined inhibition of both COX and 12-LOX pathways resulted in additive tocolytic effects.


CONCLUSIONS
5- and 12-LOX pathways modulate human myometrium contractility.
Corriveau
Stéphanie
S
Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
Rousseau
Eric
E
Berthiaume
Maryse
M
Pasquier
Jean-Charles
JC
D000328:Adult; D016227:Benzoquinones / Q000494:pharmacology; D001706:Biopsy; D015153:Blotting, Western; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009215:Myometrium / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects*
D016227:Benzoquinones; D016861:Cyclooxygenase Inhibitors; D044950:Flavanones; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; C006680:baicalein; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin