Biodiscrimination of the eight alpha-tocopherol stereoisomers results in preferential accumulation of the four 2R forms in tissues and plasma of rats.
According to the USP, 2R,4'R,8'R-alpha-tocopheryl acetate (RRR-alpha-TAc) is 1.36 times more active than all-rac-alpha-tocopheryl acetate (all-rac-alpha-TAc). The all-rac form contains 12.5% each of the stereoisomers RRR, RRS, RSR, RSS, SSS, SSR, SRS and SRR, which display different biopotencies. In the present study, female rats fed a vitamin E-deficient diet were administered 0.82 mg of all-rac-alpha-TAc or 0.60 mg of RRR-alpha-TAc daily for up to 90 d. alpha-Tocopherol concentrations in liver, brain, adipose tissue and plasma were not significantly different among groups on treatment d 64 and 90. Thus, equipotent dosages of all-rac-alpha-TAc or RRR-alpha-TAc resulted in equimolar alpha-tocopherol plasma and tissue concentrations. A comparison with rats administered tocopherol-free placebo showed that plasma and tissue alpha-tocopherol of alpha-TAc-treated rats represented alpha-tocopherol uptake during the repletion period. The eight individual alpha-tocopherol stereoisomers in tissues and plasma were determined by chiral HPLC and capillary gas chromatography. Rats treated with all-rac-alpha-TAc preferentially accumulated the four 2R alpha-tocopherol stereoisomers (15-22% each, sum of all 2R = 70-86%) in tissues and plasma. The remaining 14-30% were 2S stereoisomers with a predominance of the SRS form. In conclusion, all-rac-alpha-TAc administration led to the presence of all eight alpha-tocopherol stereoisomers in rat liver, brain, adipose tissue and plasma. The four 2R stereoisomers including RRR-alpha-tocopherol were equally and significantly enriched. This confirmed that the configuration at C-2 of the alpha-tocopherol molecule has a major impact on stereoisomer biodiscrimination. Furthermore, the results are in agreement with the hypothesis that for alpha-tocopherol stereoisomers, biopotency differences are related to corresponding differences of alpha-tocopherol concentrations.
Weiser
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F. Hoffmann-La Roche Ltd, Vitamins and Fine Chemicals, Research and Technology Development, Basel, Switzerland.
Riss
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Kormann
A W
AW
D000273:Adipose Tissue / Q000737:chemistry*; D000818:Animals; D001923:Brain Chemistry; D002849:Chromatography, Gas / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000737:chemistry*; D051381:Rats; D013237:Stereoisomerism; D014810:Vitamin E / Q000032:analysis* / Q000097:blood / Q000737:chemistry*
D014810:Vitamin E