title: A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.
abstract: A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F(2t)-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia.
authors.affiliation: Department of Obstetrics & Gynecology, the Sw. Wojciech Specialist Hospital, Independent Public Complex of Integrated Health Care Units in Gdansk, 50 Al. Jana Pawła II St., Gdansk 80-462, Poland. piotrzabul@wp.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Zabul
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland. mwozniak@gumed.edu.pl.
authors.forename: Michal
authors.initials: M
authors.lastname: Wozniak
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, VA Medical Center, Birmingham, AL 35294, USA. aslominski@uabmc.edu.
authors.forename: Andrzej T
authors.initials: AT
authors.lastname: Slominski
authors.affiliation: Department of Obstetrics & Gynecology, Medical University of Gdansk, 1A Kliniczna St., Gdansk 80-402, Poland. kpreis@gumed.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Preis
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland. m.gorska@gumed.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gorska
authors.affiliation: Department of Obstetrics & Gynecology, the Sw. Wojciech Specialist Hospital, Independent Public Complex of Integrated Health Care Units in Gdansk, 50 Al. Jana Pawła II St., Gdansk 80-462, Poland. marek@korozan.com.
authors.forename: Marek
authors.initials: M
authors.lastname: Korozan
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland. janwieruszewski@gumed.edu.pl.
authors.forename: Jan
authors.initials: J
authors.lastname: Wieruszewski
authors.affiliation: Department of Histology, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland. mzmijewski@gumed.edu.pl.
authors.forename: Michal A
authors.initials: MA
authors.lastname: Zmijewski
authors.affiliation: Department of Anesthesiology & Intensive Care, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland. ewa.zabul@gmail.com.
authors.forename: Ewa
authors.initials: E
authors.lastname: Zabul
authors.affiliation: School of Chemistry and Biochemistry, the University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. robert.tuckey@uwa.edu.au.
authors.forename: Robert
authors.initials: R
authors.lastname: Tuckey
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Kuban-Jankowska
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland. wmick@gumed.edu.pl.
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Mickiewicz
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, 1 Debinki St., Gdansk 80-211, Poland. narcyz@gumed.edu.pl.
authors.forename: Narcyz
authors.initials: N
authors.lastname: Knap
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D002112:Calcifediol / Q000494:pharmacology* / Q000627:therapeutic use; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000517:prevention & control*; D011247:Pregnancy; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014815:Vitamins; D016718:Arachidonic Acid; D002786:Cholesterol Side-Chain Cleavage Enzyme; D002112:Calcifediol
keywords: arachidonic acid hydroperoxide; isoprostanes; placenta; preeclampsia; vitamin D3