The journal of obstetrics and gynaecology research · 2013
Effect of cytochrome P-450 epoxygenase and hydroxylase metabolites on rat myometrium contractility in non-pregnancy, late pregnancy and late pregnancy under inflammatory conditions.
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Corriveau Stéphanie, Berthiaume Maryse, Girard Isabelle, Nolin Marc-Antoine, Rousseau Eric, Pasquier Jean-Charles
Аннотация
AIM: The aim of the present experimental study was to assess the tocolytic effect of eicosanoids on myometrium from non-pregnant and pregnant rats with or without an induced inflammatory condition.
METHODS: Three hundred myometrial rings were obtained by median laparotomy from 50 Sprague-Dawley rats divided into three groups: (i) non-pregnant (n = 15); (ii) pregnant in absence (n = 20); or (iii) pregnant in presence (n = 15) of lipopolysaccharide treatment, timed at 22 days of pregnancy. Spontaneous contractile activities were compared by isometric tension measurements. The effects of epoxy- and hydroxyeicosanoids derived from arachidonic acid as well as specific enzyme inhibitors were assessed. Changes were expressed as percentage of basal activity by calculating the area under the curve as a function of drug concentration and compared to the effect of the vehicle.
RESULTS: A decrease in contractile activity ranging 10-25% was observed upon addition of epoxy- and hydroxyeicosanoids. Increasing epoxyeicosanoid bioavailability by inhibiting their degradation induced a tocolytic effect in the non-pregnant group (20%) and in inflammation-induced condition (40%). There was a significant difference in reactivity between groups and pregnancy condition. Semiquantification of metabolic enzymes that produce (cytochrome P-450 epoxygenase) and degrade (soluble epoxide hydrolase) epoxyeicosanoids by western blot analysis revealed that these enzymes were mainly detected in the non-pregnant group.
CONCLUSION: Eicosanoids can modify myometrial reactivity and their presence and effects are amplified in non-pregnant and in inflammation-induced condition. Our data suggest that in contrast to prostaglandins, epoxyeicosatrienoic acids are likely involved in the quiescence phase of parturition because they reduce the rhythmic contractile activity of uterine tissues in pregnant rats.
METHODS: Three hundred myometrial rings were obtained by median laparotomy from 50 Sprague-Dawley rats divided into three groups: (i) non-pregnant (n = 15); (ii) pregnant in absence (n = 20); or (iii) pregnant in presence (n = 15) of lipopolysaccharide treatment, timed at 22 days of pregnancy. Spontaneous contractile activities were compared by isometric tension measurements. The effects of epoxy- and hydroxyeicosanoids derived from arachidonic acid as well as specific enzyme inhibitors were assessed. Changes were expressed as percentage of basal activity by calculating the area under the curve as a function of drug concentration and compared to the effect of the vehicle.
RESULTS: A decrease in contractile activity ranging 10-25% was observed upon addition of epoxy- and hydroxyeicosanoids. Increasing epoxyeicosanoid bioavailability by inhibiting their degradation induced a tocolytic effect in the non-pregnant group (20%) and in inflammation-induced condition (40%). There was a significant difference in reactivity between groups and pregnancy condition. Semiquantification of metabolic enzymes that produce (cytochrome P-450 epoxygenase) and degrade (soluble epoxide hydrolase) epoxyeicosanoids by western blot analysis revealed that these enzymes were mainly detected in the non-pregnant group.
CONCLUSION: Eicosanoids can modify myometrial reactivity and their presence and effects are amplified in non-pregnant and in inflammation-induced condition. Our data suggest that in contrast to prostaglandins, epoxyeicosatrienoic acids are likely involved in the quiescence phase of parturition because they reduce the rhythmic contractile activity of uterine tissues in pregnant rats.
Предметные рубрики MeSH
8,11,14-Eicosatrienoic AcidAnimalsCytochrome P-450 CYP2J2Cytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemDown-RegulationEnzyme InhibitorsEpoxide HydrolasesFemaleHydroxyeicosatetraenoic AcidsIn Vitro TechniquesModels, BiologicalMyometriumPregnancyPregnancy ComplicationsPregnancy MaintenanceRats, Sprague-DawleyUterine ContractionUterine Diseases