title: Deuterium-labeled phylloquinone fed to α-tocopherol-injected rats demonstrates sensitivity of low phylloquinone-containing tissues to menaquinone-4 depletion.
abstract: METHODS
  The influence of excess α-tocopherol (α-T) on tissue depletion of phylloquinone (PK) and menaquinone-4 (MK-4) was evaluated.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR, USA; Nutrition Graduate Program, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.
authors.forename: Sherry M
authors.initials: SM
authors.lastname: Farley
authors.forename: Scott W
authors.initials: SW
authors.lastname: Leonard
authors.forename: Jan F
authors.initials: JF
authors.lastname: Stevens
authors.forename: Maret G
authors.initials: MG
authors.lastname: Traber
mesh_terms: D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003903:Deuterium; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D017207:Rats, Sprague-Dawley; D010837:Vitamin K 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D014813:Vitamin K Deficiency / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism; D014815:Vitamins / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D014815:Vitamins; D024482:Vitamin K 2; C030814:menatetrenone; D010837:Vitamin K 1; D003903:Deuterium; D024502:alpha-Tocopherol
keywords: 5C- and 7C-aglycones; Bile; Brain; CEHC; CYP4F2; Heart; Urine