title: α-Tocopheryl phosphate: uptake, hydrolysis, and antioxidant action in cultured cells and mouse.
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, CD(3), at position 5 of the chroman ring (α-TP(CD3)). The hydrolysis of α-TP(CD3) was followed by measuring α-tocopherol containing the CD(3) 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.
authors: Health Research Institute, National Institute of Advanced Industrial Science & Technology, Ikeda, Osaka 563-8577, Japan.
authors: Keiko
authors: K
authors: Nishio
authors: Noriko
authors: N
authors: Ishida
authors: Yoshiro
authors: Y
authors: Saito
authors: Yoko
authors: Y
authors: Ogawa-Akazawa
authors: Mototada
authors: M
authors: Shichiri
authors: Yasukazu
authors: Y
authors: Yoshida
authors: Yoshihisa
authors: Y
authors: Hagihara
authors: Noriko
authors: N
authors: Noguchi
authors: John
authors: J
authors: Chirico
authors: Jeffrey
authors: J
authors: Atkinson
authors: Etsuo
authors: E
authors: Niki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D003903:Deuterium / Q000138:chemical synthesis; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005609:Free Radicals; C012552:alpha-tocopherol phosphate; D003903:Deuterium; D024502:alpha-Tocopherol