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Vitamin E Injections Decrease Tissue Vitamin K in Rats
Author(s) -
Farley Sherry M,
Leornard Scott W,
Labut Edwin M,
Raines Hannah F,
Card David J,
Harrington Dominic J,
Mustacich Debbie J,
Traber Maret G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.996.16
Subject(s) - medicine , endocrinology , menadione , chemistry , excretion , kidney , vitamin , metabolite , cytochrome p450 , xenobiotic , metabolism , biology , enzyme , biochemistry
To test the mechanism by which α‐tocopherol (α‐T) decreases vitamin K status, rats were fed for 2.5 w phylloquinone (PK) or menadione (MN)‐containing diets (2 μmol/kg). From 10 d, rats were subcutaneously injected daily with α‐T (100 mg/kg) or vehicle, then sacrificed 24 h after the 7 th injection. Urine collected during the injection period was analyzed for vitamin metabolites; tissue PK and menaquinone‐4 (MK‐4), and hepatic expression of enzymes and transporters were also analyzed. Irrespective of diet, α‐T injections decreased MK‐4 in brain, lung, & kidney; and PK in kidney and lung. However, these decreases were not accompanied by increased urinary 5C‐ or 7C‐aglycone, or MN excretion; however, α‐T metabolite excretion increased ≥100 fold. Moreover, α‐T down‐regulated gene expression of various cytochrome P450s and up‐regulated expression of xenobiotic transporters. Thus, high doses of α‐T decrease tissue vitamin K concentrations, but these decreases are not likely a result of increased metabolism, but rather reflect an increased gene expression of xenobiotic transporters, which could potentiate tissue vitamin K loss and increase its biliary excretion. Grant Funding Source : USDA NRI‐2008‐01875