Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

详细信息    查看全文

• 作者：Sté ; phanie Corriveau ; Simon Blouin ; Elyse Burt ; Eric Rousseau ; Jean-Charles Pasquier ; ^{jean-charles.pasquier@usherbrooke.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Inflammation ; Leukotrienes ; Montelukast ; Pregnant rats ; Tocolytics ; Uterine contractions
• 刊名：European Journal of Obstetrics & Gynecology and Reproductive Biology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：206
• 期：Complete
• 页码：92-98
• 全文大小：1684 K

文摘

The potency of acute montelukast treatment, a leukotriene receptor antagonist, has been demonstrated as tocolytic on m>in vitrom> myometrial contractility. This study assessed the ability of a 48 h montelukast treatment to modify m>in vitrom> contractions under inflammatory conditions in a pregnant rat model.

Study design

Pregnant Sprague-Dawley rats were injected intraperitoneally (gestational days 20–22) with lipopolysaccharides (LPS) 200 μg/kg (4 treatments at 12 h intervals) alone or combined with montelukast 10 mg/kg/day or a saline solution for a 48 h period. Uterine rings (m>nm> = 72) were obtained by median laparotomy at day 22. Spontaneous contractile activities were compared using pharmacological compounds (oxytocin, nifedipine) along with assessment of contractile parameters. Myometrial subcellular fractions were also analyzed by Western blot to quantify oxytocin, cysteinyl leukotriene receptors and inflammation markers.

Results

In m>in vitrom> experiments, the area under the curve, the amplitude and the duration of phasic contractions were significantly reduced following 48 h of LPS + montelukast treatment comparatively to the LPS group. Moreover, in this same group, oxytocin (10^&minus;9–10^&minus;7 M) largely decreased uterine sensitivity (m>pm> = 0.04). Following LPS and montelukast treatment, the tocolytic effectiveness of nifedipine (10^&minus;9–10^&minus;7 M) was increased (m>pm> < 0.01). Western blot analysis confirmed the presence of type 1 CysLT receptors in all treated groups. Hence, montelukast treatment restored TNF-α and COX-2 basal levels.

Conclusion

Our results strongly suggest that montelukast treatment could facilitate a relative uterine quiescence by decreasing its sensitivity to uterotonic agent or by increasing tocolytic efficiency under proinflammatory conditions.