A proposed molecular mechanism of high-dose vitamin D3 supplementation in prevention and treatment of preeclampsia

P. Zabul, M. Wozniak, A.T. Slominski, K. Preis, M. Gorska, M. Korozan, J. Wieruszewski, M.A. Zmijewski, E. Zabul, Robert Tuckey, A. Kuban-Jankowska, W. Mickiewicz, N. Knap

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Abstract

© 2015 by the authors; licensee MDPI, Basel, Switzerland. A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-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.
Original languageEnglish
Pages (from-to)13043-13064
JournalInternational Journal of Molecular Sciences
Volume16
Issue number6
DOIs
Publication statusPublished - 2015

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Cholesterol Side-Chain Cleavage Enzyme
vitamins
Cholecalciferol
Vitamins
cytochromes
Pre-Eclampsia
Proteins
dosage
Progesterone
creatinine
Calcifediol
Hydroxylation
Mitochondria
Oxidative stress
mitochondria
Disintegration
Lipid Peroxides
peroxides
disintegration
metabolism

Cite this

Zabul, P. ; Wozniak, M. ; Slominski, A.T. ; Preis, K. ; Gorska, M. ; Korozan, M. ; Wieruszewski, J. ; Zmijewski, M.A. ; Zabul, E. ; Tuckey, Robert ; Kuban-Jankowska, A. ; Mickiewicz, W. ; Knap, N. / A proposed molecular mechanism of high-dose vitamin D3 supplementation in prevention and treatment of preeclampsia. In: International Journal of Molecular Sciences. 2015 ; Vol. 16, No. 6. pp. 13043-13064.
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author = "P. Zabul and M. Wozniak and A.T. Slominski and K. Preis and M. Gorska and M. Korozan and J. Wieruszewski and M.A. Zmijewski and E. Zabul and Robert Tuckey and A. Kuban-Jankowska and W. Mickiewicz and N. Knap",
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Zabul, P, Wozniak, M, Slominski, AT, Preis, K, Gorska, M, Korozan, M, Wieruszewski, J, Zmijewski, MA, Zabul, E, Tuckey, R, Kuban-Jankowska, A, Mickiewicz, W & Knap, N 2015, 'A proposed molecular mechanism of high-dose vitamin D3 supplementation in prevention and treatment of preeclampsia' International Journal of Molecular Sciences, vol. 16, no. 6, pp. 13043-13064. https://doi.org/10.3390/ijms160613043

A proposed molecular mechanism of high-dose vitamin D3 supplementation in prevention and treatment of preeclampsia. / Zabul, P.; Wozniak, M.; Slominski, A.T.; Preis, K.; Gorska, M.; Korozan, M.; Wieruszewski, J.; Zmijewski, M.A.; Zabul, E.; Tuckey, Robert; Kuban-Jankowska, A.; Mickiewicz, W.; Knap, N.

In: International Journal of Molecular Sciences, Vol. 16, No. 6, 2015, p. 13043-13064.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A proposed molecular mechanism of high-dose vitamin D3 supplementation in prevention and treatment of preeclampsia

AU - Zabul, P.

AU - Wozniak, M.

AU - Slominski, A.T.

AU - Preis, K.

AU - Gorska, M.

AU - Korozan, M.

AU - Wieruszewski, J.

AU - Zmijewski, M.A.

AU - Zabul, E.

AU - Tuckey, Robert

AU - Kuban-Jankowska, A.

AU - Mickiewicz, W.

AU - Knap, N.

PY - 2015

Y1 - 2015

N2 - © 2015 by the authors; licensee MDPI, Basel, Switzerland. A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-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.

AB - © 2015 by the authors; licensee MDPI, Basel, Switzerland. A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-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.

U2 - 10.3390/ijms160613043

DO - 10.3390/ijms160613043

M3 - Article

VL - 16

SP - 13043

EP - 13064

JO - Internation Journal of Molecular Sciences

JF - Internation Journal of Molecular Sciences

SN - 1422-0067

IS - 6

ER -