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A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

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 - Int J Mol Sci (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Vitamin D3 (25(OH)D3) plasma levels in preeclamptic women vs. control. No significant difference between groups was found.
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ijms-16-13043-f002: Vitamin D3 (25(OH)D3) plasma levels in preeclamptic women vs. control. No significant difference between groups was found.

Mentions: The urinary levels of 15-F2t-isoP in the preeclamptic group were significantly higher relative to the control group (3.05 vs. 2.00 ng/mg creatinine; p < 0.01) (Figure 1). This finding supports the hypothesis that biological effects of an oxidative stress-mediated increases in placental generation of thromboxane A2 may be enhanced by 15-F2t-isoP isoprostane-dependent activation of the thromboxane A2 receptor [8]. The plasma levels of 25(OH)D3 in both groups were below the clinical reference range of 30 ng/mL with no difference between the groups (mean 16.8 ng/mL) (Figure 2). There was no correlation between the urinary excretion of 15-F2t-isoP and plasma levels of 25(OH)D3 in either of the study groups.


A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

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 - Int J Mol Sci (2015)

Vitamin D3 (25(OH)D3) plasma levels in preeclamptic women vs. control. No significant difference between groups was found.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490485&req=5

ijms-16-13043-f002: Vitamin D3 (25(OH)D3) plasma levels in preeclamptic women vs. control. No significant difference between groups was found.
Mentions: The urinary levels of 15-F2t-isoP in the preeclamptic group were significantly higher relative to the control group (3.05 vs. 2.00 ng/mg creatinine; p < 0.01) (Figure 1). This finding supports the hypothesis that biological effects of an oxidative stress-mediated increases in placental generation of thromboxane A2 may be enhanced by 15-F2t-isoP isoprostane-dependent activation of the thromboxane A2 receptor [8]. The plasma levels of 25(OH)D3 in both groups were below the clinical reference range of 30 ng/mL with no difference between the groups (mean 16.8 ng/mL) (Figure 2). There was no correlation between the urinary excretion of 15-F2t-isoP and plasma levels of 25(OH)D3 in either of the study groups.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus