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Spatiotemporal biodistribution of α-tocopherol is impacted by the source of 13C-labeled α-tocopherol in mice following a single oral dose
Nutrition Research ( IF 3.4 ) Pub Date : 2021-07-25 , DOI: 10.1016/j.nutres.2021.07.005
Sookyoung Jeon 1 , Qiyao Li 2 , Katherine M Ranard 1 , Stanislav S Rubakhin 2 , Jonathan V Sweedler 2 , Matthew J Kuchan 3 , John W Erdman 4
Affiliation  

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.



中文翻译:

α-生育酚的时空生物分布受到单次口服剂量后小鼠体内 13C 标记的 α-生育酚来源的影响

天然 ( RRR -) α-生育酚 (αT) 比合成的(全是外消旋的,全是外消旋的)αT 更具生物活性,但对 2 种 αT 来源的组织动力学知之甚少。我们使用13 C- RRR -αT 或13 C- all rac检测了年轻、维生素 E 略微缺乏的小鼠组织中天然与合成 αT 的时间过程生物积累。-αT 示踪剂。在实验 1 中,给 3 周大的雄性野生型小鼠喂食缺乏维生素 E 的饮食 0、1、2 或 3 周(n = 5/时间点)。通过 HPLC-PDA 分析组织 αT 水平。喂养缺乏维生素 E 的饮食长达 3 周会降低所有分析组织中的总 αT 浓度,但大脑保持其 αT 水平。在实验 2 中,在 2 周的 αT 耗竭期之后,给予单次口服剂量 0.5 mg 的13 C - RRR -αT 或13 C - all rac -αT。在给药后 12 小时、1、2 和 4 天,收集血清和多个组织(n = 3/时间点)。αT通过HPLC-PDA定量,13 C-αT富集通过LC-MS测定。13的两个来源C-αT 在给药后 12 小时达到最高血清水平。给药后 1 天血清中的13 C- RRR -αT 水平显着高于给药后 2 天在心脏、肺和肾中的13 C- all rac -αT。在脑中,13 C - RRR -αT 浓度在给药后 2 天和 4 天显着高于13 C - all rac -αT。在给药后 4 天,13 C-αT 水平在检查组织中的 2 种来源之间相似,除了脑和脂肪组织,其中13 C - RRR -αT 较高。总之,随着时间的推移,αT 生物蓄积在很大程度上取决于 αT 来源和组织类型。

更新日期:2021-08-23
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