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Deuterium-labeled phylloquinone fed to α-tocopherol-injected rats demonstrates sensitivity of low phylloquinone-containing tissues to menaquinone-4 depletion

Authors

  • Sherry M. Farley,

    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. Nutrition Graduate Program, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA
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  • Scott W. Leonard,

    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
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  • Jan F. Stevens,

    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. College of Pharmacy, Oregon State University, Corvallis, OR, USA
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  • Maret G. Traber

    Corresponding author
    1. Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
    2. Nutrition Graduate Program, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA
    • Correspondence: Professor Maret G. Traber, Linus Pauling Institute, 307 Linus Pauling Science Center, Oregon State University, Corvallis, OR 97331, USA

      E-mail: maret.traber@oregonstate.edu

      Fax: +1-541-737-5077

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Abstract

Scope

The influence of excess α-tocopherol (α-T) on tissue depletion of phylloquinone (PK) and menaquinone-4 (MK-4) was evaluated.

Methods and results

Rats (n = 5 per group) were fed deuterium-labeled PK (2 μmol/kg diet) for 17 days, thereby labeling the conversion from deuterium-labeled PK to d4-MK-4. Then they were injected subcutaneously daily for the last 7 days with saline, vehicle, or α-T (100 mg/kg body weight). α-T injections (i) increased α-T concentrations by tenfold in liver, doubled them in plasma and most tissues, but they were unchanged in brain; (ii) increased the α-T metabolite, carboxyethyl hydroxychromanol (α-CEHC) concentrations: >25-fold in liver and kidney, tenfold in plasma and lung, and 50-fold in heart; brain contained detectable α-CEHC (0.26 ± 0.03 nmol/g) only in α-T-injected animals; and (iii) depleted most tissues’ vitamin K. Compared with vehicle-injected rats, brains from α-T rats contained half the total vitamin K (10.3 ± 0.5 versus 21 ± 2 pmol/g, p = 0.0002) and one-third the d4-MK-4 (5.8 ± 0.5 versus 14.6 ± 1.7 pmol/g, p = 0.0002). Tissues with high PK concentrations (liver, 21–30 pmol/g and heart, 28–50 pmol/g) were resistant to K depletion.

Conclusion

We propose that α-T-dependent vitamin K depletion is likely mediated at an intermediate step in MK-4 production; thus, tissues with high PK are unaffected.

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