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    The effects of flavonoids on human first trimester trophoblast spheroidal stem cell self-renewal, invasion and JNK/p38 MAPK activation: Understanding the cytoprotective effects of these phytonutrients against oxidative stress

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    BCP-D-19-00272 - Final.pdf
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    Authors
    sivasubramaniam, shiva
    dickenson, John
    Ebegoni, \vernon
    Balahamar, Reham
    Affiliation
    Nottingham Trent University
    Issue Date
    2019-04-22
    
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    Abstract
    Adequate invasion and complete remodelling of the maternal spiral arteries by the invading extravillous trophoblasts are the major determinants of a successful pregnancy. Increase in oxidative stress during pregnancy has been linked to the reduction in trophoblast invasion and incomplete conversion of the maternal spiral arteries, resulting in pregnancy complications such as pre-eclampsia, intrauterine growth restriction, and spontaneous miscarriages resulting in foetal/maternal mortality. The use of antioxidant therapy (vitamin C and E) and other preventative treatments (such as low dose aspirin) have been ineffective in preventing pre-eclampsia. Also, as the majority of antihypertensive drugs pose side effects, choosing an appropriate treatment would depend upon the efficacy and safety of mother/foetus. Since pre-eclampsia is mainly linked to placental oxidative stress, new diet-based antioxidants can be of use to prevent this condition. The antioxidant properties of flavonoids (naturally occurring phenolic compounds which are ubiquitously distributed in fruits and vegetables) have been well documented in non-trophoblast cells. Therefore, this study aimed to investigate the effects of flavonoids (quercetin, hesperidin) and their metabolites (Quercetin 3-O-β-glucuronide and hesperetin), either alone or in combination, on first trimester trophoblast cell line HTR-8/SVneo during oxidative stress. The data obtained from this study indicate that selected flavonoids, their respective metabolites significantly reduced the levels of reduced glutathione (p < 0.0001) during HR-induced oxidative stress. These flavonoids also inhibited the activation of pro-apoptotic kinases (p38 MAPK and c-Jun N-terminal kinase) during HR-induced phosphorylation. In addition, they enhanced spheroid stem-like cell generation from HTR8/SVneo cells, aiding their invasion. Our data suggest that dietary intake of food rich in quercetin or hesperidin during early pregnancy can significantly improve trophoblast (placenta) health and function against oxidative stress.
    Citation
    Ebegboni, V.J., Balahmar, R.M., Dickenson, J.M. and Sivasubramaniam, S.D., (2019). T'he effects of flavonoids on human first trimester trophoblast spheroidal stem cell self-renewal, invasion and JNK/p38 MAPK activation: Understanding the cytoprotective effects of these phytonutrients against oxidative stress'. Biochemical pharmacology, 164, pp. 289-298. DOI: 10.1016/j.bcp.2019.04.023
    Publisher
    Elsivier
    Journal
    Biochemical Pharmacology
    URI
    http://hdl.handle.net/10545/623804
    DOI
    10.1016/j.bcp.2019.04.023
    Additional Links
    https://www.ncbi.nlm.nih.gov/pubmed/31022396
    https://www.sciencedirect.com/science/article/pii/S0006295219301583
    Type
    Article
    Language
    en
    ISSN
    00062952
    EISSN
    18732968
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.bcp.2019.04.023
    Scopus Count
    Collections
    Human Sciences Research Centre

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