Misoprostol modulates the gene expression prostaglandin E2 and oxidative stress markers in myometrial cells

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• 作者：Cristine Kolling Konopka^a ; ^b ; ^{cristinekollingkonopka@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; ^{fernandabarbisan@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Verô ; nica Farina Azzolin^a ; ^{azzolinveronica@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Francine Carla Cadon&aacute ; ^c ; ^{fran.cine.bio@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Alencar Kolinski Machado^a ; ^{alencarkolinski@yahoo.com.br" class="auth_mail" title="E-mail the corresponding author} ; Eduardo Bortoluzzi Dornelles^c ; ^{dornellesedu@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Fernanda Barbisan^a ; ^{fernandabarbisan@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Ivana Beatrice Mâ ; nica da Cruz^d ; ^{ibmcruz@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：mRNA ; Prostaglandin receptors ; Term pregnancy ; Myometrium ; Uterus ; Pharmacogenomic
• 刊名：Prostaglandins and Other Lipid Mediators
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：126
• 期：Complete
• 页码：38-45
• 全文大小：1058 K

文摘

Misoprostol, prostaglandin E1 analogue, used for labour induction. However, one-third of patients who have labour induced with prostaglandins do not reach vaginal delivery. The differential expression of prostaglandin receptors in myometrial cells could account for this differential response. Since delivery physiology also involves modulation of oxidative metabolism that can be potentially affected by pharmacological drugs, in the present investigation the role of misoprostol on expression of prostaglandin receptors, and oxidative markers of myometrial cells was evaluated. Samples of myometrial tissues procured from women with spontaneous (SL) and nonspontaneous (NSL) labours were cultured in vitro and exposed to different concentrations of misoprostol. Gene expression was evaluated by qRT-PCR and oxidative biomarkers were evaluated by spectrophotometric and fluorometric analysis. Cells from SL women presented greater responsiveness to misoprostol, since an upregulation of genes related to increased muscle contraction was observed. Otherwise, cells from NSL women had low responsiveness to misoprostol exposure or even a suppressive effect on the expression of these genes. Oxidative biomarkers that previously have been related to labour physiology were affected by misoprostol treatment: lipoperoxidation and protein carbonylation (PC). However, a decrease in lipoperoxidation was observed only in SL cells treated with low concentrations of misoprostol, whereas a decrease of PC occurred in all samples treated with different misoprostol concentrations. The results suggest a pharmacogenetic effect of misoprostol in labour induction involving differential regulation of EP receptor genes, as well as some minor differential modulation of oxidative metabolism in myometrial cells.