Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease
Previously, we demonstrated that the proton pump inhibitor, esomeprazole magnesium hydrate (MH), could have potential as a repurposed treatment against preeclampsia, a serious obstetric condition. In this study we investigate the difference in the preclinical effectiveness between 100 µM of esomepra...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/17/9533 |
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| author | Natasha de Alwis Bianca R. Fato Sally Beard Natalie K. Binder Tu’uhevaha J. Kaitu’u-Lino Kenji Onda Natalie J. Hannan |
| author_facet | Natasha de Alwis Bianca R. Fato Sally Beard Natalie K. Binder Tu’uhevaha J. Kaitu’u-Lino Kenji Onda Natalie J. Hannan |
| author_sort | Natasha de Alwis |
| collection | DOAJ |
| description | Previously, we demonstrated that the proton pump inhibitor, esomeprazole magnesium hydrate (MH), could have potential as a repurposed treatment against preeclampsia, a serious obstetric condition. In this study we investigate the difference in the preclinical effectiveness between 100 µM of esomeprazole MH and its hydration isomer, esomeprazole magnesium trihydrate (MTH). Here, we found that both treatments reduced secretion of sFLT-1 (anti-angiogenic factor) from primary cytotrophoblast, but only esomeprazole MH reduced sFLT-1 secretion from primary human umbilical vein endothelial cells (assessed via ELISA). Both drugs could mitigate expression of the endothelial dysfunction markers, vascular cell adhesion molecule-1 and endothelin-1 (via qPCR). Neither esomeprazole MH nor MTH quenched cytotrophoblast reactive oxygen species production in response to sodium azide (ROS assay). Finally, using wire myography, we demonstrated that both compounds were able to induce vasodilation of human omental arteries at 100 µM. Esomeprazole is safe to use in pregnancy and a candidate treatment for preeclampsia. Using primary human tissues and cells, we validated that esomeprazole is effective in enhancing vascular relaxation, and can reduce key factors associated with preeclampsia, including sFLT-1 and endothelial dysfunction. However, esomeprazole MH was more efficacious than esomeprazole MTH in our in vitro studies. |
| first_indexed | 2024-03-10T01:47:40Z |
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| id | doaj.art-f7301bda208f48c6a4569e09d898b764 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:47:40Z |
| publishDate | 2022-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f7301bda208f48c6a4569e09d898b7642023-11-23T13:12:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012317953310.3390/ijms23179533Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of DiseaseNatasha de Alwis0Bianca R. Fato1Sally Beard2Natalie K. Binder3Tu’uhevaha J. Kaitu’u-Lino4Kenji Onda5Natalie J. Hannan6Therapeutics Discovery and Vascular Function Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, VIC 3084, AustraliaTherapeutics Discovery and Vascular Function Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, VIC 3084, AustraliaTherapeutics Discovery and Vascular Function Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, VIC 3084, AustraliaTherapeutics Discovery and Vascular Function Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, VIC 3084, AustraliaDiagnostics Discovery and Reverse Translation in Pregnancy Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, VIC 3084, AustraliaDepartment of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, JapanTherapeutics Discovery and Vascular Function Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, VIC 3084, AustraliaPreviously, we demonstrated that the proton pump inhibitor, esomeprazole magnesium hydrate (MH), could have potential as a repurposed treatment against preeclampsia, a serious obstetric condition. In this study we investigate the difference in the preclinical effectiveness between 100 µM of esomeprazole MH and its hydration isomer, esomeprazole magnesium trihydrate (MTH). Here, we found that both treatments reduced secretion of sFLT-1 (anti-angiogenic factor) from primary cytotrophoblast, but only esomeprazole MH reduced sFLT-1 secretion from primary human umbilical vein endothelial cells (assessed via ELISA). Both drugs could mitigate expression of the endothelial dysfunction markers, vascular cell adhesion molecule-1 and endothelin-1 (via qPCR). Neither esomeprazole MH nor MTH quenched cytotrophoblast reactive oxygen species production in response to sodium azide (ROS assay). Finally, using wire myography, we demonstrated that both compounds were able to induce vasodilation of human omental arteries at 100 µM. Esomeprazole is safe to use in pregnancy and a candidate treatment for preeclampsia. Using primary human tissues and cells, we validated that esomeprazole is effective in enhancing vascular relaxation, and can reduce key factors associated with preeclampsia, including sFLT-1 and endothelial dysfunction. However, esomeprazole MH was more efficacious than esomeprazole MTH in our in vitro studies.https://www.mdpi.com/1422-0067/23/17/9533preeclampsiaplacentaesomeprazoletrophoblastsFLT-1 |
| spellingShingle | Natasha de Alwis Bianca R. Fato Sally Beard Natalie K. Binder Tu’uhevaha J. Kaitu’u-Lino Kenji Onda Natalie J. Hannan Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease International Journal of Molecular Sciences preeclampsia placenta esomeprazole trophoblast sFLT-1 |
| title | Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease |
| title_full | Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease |
| title_fullStr | Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease |
| title_full_unstemmed | Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease |
| title_short | Assessment of the Proton Pump Inhibitor, Esomeprazole Magnesium Hydrate and Trihydrate, on Pathophysiological Markers of Preeclampsia in Preclinical Human Models of Disease |
| title_sort | assessment of the proton pump inhibitor esomeprazole magnesium hydrate and trihydrate on pathophysiological markers of preeclampsia in preclinical human models of disease |
| topic | preeclampsia placenta esomeprazole trophoblast sFLT-1 |
| url | https://www.mdpi.com/1422-0067/23/17/9533 |
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