Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone
Article first published online: 18 JUN 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 6, pages 912–922, June 2012
How to Cite
Farley, S. M., Leonard, S. W., Labut, E. M., Raines, H. F., Card, D. J., Harrington, D. J., Mustacich, D. J. and Traber, M. G. (2012), Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone. Mol. Nutr. Food Res., 56: 912–922. doi: 10.1002/mnfr.201100751
- Issue published online: 18 JUN 2012
- Article first published online: 18 JUN 2012
- Manuscript Accepted: 15 FEB 2012
- Manuscript Revised: 8 FEB 2012
- Manuscript Received: 13 NOV 2011
Vol. 57, Issue 6, 1115, Article first published online: 7 JUN 2013
- ABC transporters;
- 5C- and 7C-aglycones;
- Xenobiotic pathways
The mechanism for increased bleeding and decreased vitamin K status accompanying vitamin E supplementation is unknown. We hypothesized that elevated hepatic α-tocopherol (α-T) concentrations may stimulate vitamin K metabolism and excretion. Furthermore, α-T may interfere with the side chain removal of phylloquinone (PK) to form menadione (MN) as an intermediate for synthesis of tissue-specific menaquinone-4 (MK-4).
Methods and results
In order to investigate these hypotheses, rats were fed phylloquinone (PK) or menadione (MN) containing diets (2 μmol/kg) for 2.5 weeks. From day 10, rats were given daily subcutaneous injections of either α-T (100 mg/kg) or vehicle and were sacrificed 24 h after the seventh injection. Irrespective of diet, α-T injections decreased MK-4 concentrations in brain, lung, kidney, and heart; and PK in lung. These decreases were not accompanied by increased excretion of urinary 5C- or 7C-aglycone vitamin K metabolites, however, the urinary α-T metabolite (α-CEHC) increased ≥100-fold. Moreover, α-T increases were accompanied by downregulation of hepatic cytochrome P450 expression and modified expression of tissue ATP-binding cassette transporters.
Thus, in rats, high tissue α-T depleted tissue MK-4 without significantly increasing urinary vitamin K metabolite excretion. Changes in tissue MK-4 and PK levels may be a result of altered regulation of transporters.