Spatiotemporal biodistribution of α-tocopherol is impacted by the source of 13C-labeled α-tocopherol in mice following a single oral dose

Abstract

Natural (RRR-) α-tocopherol (αT) is more bioactive than synthetic (all racemic, all rac-) αT, but not enough is known about the tissue kinetics of the 2 αT sources. We examined the time-course bioaccumulation of natural versus synthetic αT in tissues of young, marginally vitamin E-deficient mice using ¹³C-RRR-αT or ¹³C-all rac-αT tracers. In experiment 1, 3-week old male wild-type mice were fed a vitamin E-deficient diet for 0, 1, 2, or 3 weeks (n = 5/time point). Tissue αT levels were analyzed by HPLC-PDA. Feeding a vitamin E-deficient diet for up to 3 weeks decreased total αT concentrations in all analyzed tissues except the brain, which maintained its αT level. In experiment 2, a 2-week αT-depletion period was followed by administration of a single oral dose of 0.5 mg of ¹³C-RRR-αT or ¹³C-all rac-αT. At 12 hr, 1, 2, and 4 days post-dose, serum and multiple tissues were collected (n = 3/time point). αT was quantified by HPLC-PDA, and ¹³C-αT enrichment was determined by LC-MS. Both sources of ¹³C-αT reached maximum serum levels at 12 hr post-dose. ¹³C-RRR-αT levels were significantly higher than ¹³C-all rac-αT in serum at 1 d post-dose, and in heart, lungs, and kidney at 2d post-dose. In brain, ¹³C-RRR-αT concentrations were significantly higher than ¹³C-all rac-αT at 2 and 4 d post-dose. At 4 d post-dose, ¹³C-αT levels were similar between the 2 sources in examined tissues except for brain and adipose tissue where ¹³C-RRR-αT was higher. In conclusion, αT bioaccumulation over time varied substantially depending on αT source and tissue type.

Keywords: All rac-α-tocopherol; Bioaccumulation; Isotopic tracer; Mass spectrometry; RRR-α-tocopherol; Vitamin E.