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Open AccessArticle

Hydroxychloroquine Mitigates the Production of 8-Isoprostane and Improves Vascular Dysfunction: Implications for Treating Preeclampsia

1
Department of Obstetrics and Gynaecology, School of Clinical Sciences, Monash University, Monash Medical Centre, Clayton, Victoria 3168, Australia
2
The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
3
Department of Obstetrics and Gynaecology, Faculty of Medicine, National University of Malaysia, Kuala Lumpur 56000, Malaysia
4
Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria 3052, Australia
*
Authors to whom correspondence should be addressed.
Current address: Cardiovascular Research Program, Monash Biomedicine Discovery Institute and Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Int. J. Mol. Sci. 2020, 21(7), 2504; https://doi.org/10.3390/ijms21072504
Received: 19 March 2020 / Revised: 31 March 2020 / Accepted: 31 March 2020 / Published: 3 April 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Preeclampsia)
In preeclampsia, widespread maternal endothelial dysfunction is often secondary to excessive generation of placental-derived anti-angiogenic factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), along with proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) and activin A, understanding of which offers potential opportunities for the development of novel therapies. The antimalarial hydroxychloroquine is an anti-inflammatory drug improving endothelial homeostasis in lupus. It has not been explored as to whether it can improve placental and endothelial function in preeclampsia. In this in vitro study, term placental explants were used to assess the effects of hydroxychloroquine on placental production of sFlt-1, sEng, TNF-α, activin A, and 8-isoprostane after exposure to hypoxic injury or oxidative stress. Similarly, human umbilical vein endothelial cells (HUVECs) were used to assess the effects of hydroxychloroquine on in vitro markers of endothelial dysfunction. Hydroxychloroquine had no effect on the release of sFlt-1, sEng, TNF-α, activin A, or 8-isoprostane from placental explants exposed to hypoxic injury or oxidative stress. However, hydroxychloroquine mitigated TNF-α-induced HUVEC production of 8-isoprostane and Nicotinanamide adenine dinucleotide phosphate (NADPH) oxidase expression. Hydroxychloroquine also mitigated TNF-α and preeclamptic serum-induced HUVEC monolayer permeability and rescued the loss of zona occludens protein zona occludens 1 (ZO-1). Although hydroxychloroquine had no apparent effects on trophoblast function, it may be a useful endothelial protectant in women presenting with preeclampsia. View Full-Text
Keywords: hydroxychloroquine; preeclampsia; sFlt-1; sEng; TNF-α; endothelial dysfunction hydroxychloroquine; preeclampsia; sFlt-1; sEng; TNF-α; endothelial dysfunction
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MDPI and ACS Style

Rahman, R.A.; Murthi, P.; Singh, H.; Gurungsinghe, S.; Leaw, B.; Mockler, J.C.; Lim, R.; Wallace, E.M. Hydroxychloroquine Mitigates the Production of 8-Isoprostane and Improves Vascular Dysfunction: Implications for Treating Preeclampsia. Int. J. Mol. Sci. 2020, 21, 2504. https://doi.org/10.3390/ijms21072504

AMA Style

Rahman RA, Murthi P, Singh H, Gurungsinghe S, Leaw B, Mockler JC, Lim R, Wallace EM. Hydroxychloroquine Mitigates the Production of 8-Isoprostane and Improves Vascular Dysfunction: Implications for Treating Preeclampsia. International Journal of Molecular Sciences. 2020; 21(7):2504. https://doi.org/10.3390/ijms21072504

Chicago/Turabian Style

Rahman, Rahana A.; Murthi, Padma; Singh, Harmeet; Gurungsinghe, Seshini; Leaw, Bryan; Mockler, Joanne C.; Lim, Rebecca; Wallace, Euan M. 2020. "Hydroxychloroquine Mitigates the Production of 8-Isoprostane and Improves Vascular Dysfunction: Implications for Treating Preeclampsia" Int. J. Mol. Sci. 21, no. 7: 2504. https://doi.org/10.3390/ijms21072504

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