Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone.
METHODS
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).


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.


CONCLUSIONS
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.
School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA.
Sherry M
SM
Farley
Scott W
SW
Leonard
Edwin M
EM
Labut
Hannah F
HF
Raines
David J
DJ
Card
Dominic J
DJ
Harrington
Debbie J
DJ
Mustacich
Maret G
MG
Traber
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002839:Chromans / Q000652:urine; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007279:Injections, Subcutaneous; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011422:Propionates / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014810:Vitamin E / Q000009:adverse effects*; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D024483:Vitamin K 3 / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000652:urine
D018528:ATP-Binding Cassette Transporters; D002839:Chromans; D011422:Propionates; D012333:RNA, Messenger; C483420:carboxyethyl-hydroxychroman; D024482:Vitamin K 2; D014810:Vitamin E; C030814:menatetrenone; C084852:2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman; D024483:Vitamin K 3; D010837:Vitamin K 1; D003577:Cytochrome P-450 Enzyme System; D024502:alpha-Tocopherol