α-Tocopheryl phosphate: Uptake, hydrolysis, and antioxidant action in cultured cells and mouse

Keiko Nishio, Noriko Ishida, Yoshiro Saito, Yoko Ogawa-Akazawa, Mototada Shichiri, Yasukazu Yoshida, Yoshihisa Hagihara, Noriko Noguchi, John Chirico, Jeffrey Atkinson, Etsuo Niki

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

α-Tocopheryl phosphate (α-TP), a water-soluble analogue of α-tocopherol, is found in humans, animals, and plants. α-TP is resistant to both acid and alkaline hydrolysis and may exert its own function in this form in vivo. In this study, the uptake, hydrolysis, and antioxidant action of α-TP were measured using α-TP with a deuterated methyl group, CD3, at position 5 of the chroman ring (α-TP(CD3)). The hydrolysis of α-TP(CD3) was followed by measuring α-tocopherol containing the CD3 group, α-T(CD3), in comparison to unlabeled α-tocopherol, α-T(CH3). α-TP(CD3) was incubated with cultured cells, and the intracellular α-T(CD3) formed was measured with HPLC-ECD and GC-MS. α-TP(CD3) was also administered to mice for 4 weeks by mixing in the diet, and α-T(CD3) was measured in plasma, liver, brain, heart, and testis to compare with endogenous unlabeled α-T(CH3). It was found that α-TP(CD3) was taken in and hydrolyzed readily to α-T(CD3) in cultured cells and in mice. The hydrolysis of α-TP(CD3) in cell culture medium was not observed. α-TP protected primary cortical neuronal cells from glutamate-induced cytotoxicity, and α-TP given to mice reduced the levels of lipid peroxidation products in plasma and liver. These results suggest that α-TP is readily hydrolyzed in vivo to α-T, which acts as an antioxidant, and that α-TP may be used as a water-soluble α-T precursor in intravenous fluids, in eye drops, or as a dietary supplement.

Original languageEnglish
Pages (from-to)1794-1800
Number of pages7
JournalFree Radical Biology and Medicine
Volume50
Issue number12
DOIs
Publication statusPublished - 2011 Jun 15
Externally publishedYes

Keywords

  • Antioxidant
  • Free radicals
  • Lipid peroxidation
  • Oxidative stress
  • Tocopheryl phosphate
  • Vitamin E

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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