Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, IL.
Department of Chemistry, University of Illinois at Urbana-Champaign, IL; The Beckman Institute, University of Illinois at Urbana-Champaign, IL.
Nutr Res. 2019 Jan;61:102-108. doi: 10.1016/j.nutres.2018.10.007. Epub 2018 Oct 28.
Despite the growing awareness regarding lutein's putative roles in eyes and brain, its pharmacokinetics and tissue distribution in primates have been poorly understood. We hypothesized that C-lutein will be differentially distributed into tissues of an adult rhesus macaque (Macaca mulatta) 3 days following a single oral dose. After a year of prefeeding a diet supplemented with unlabeled lutein (1 μmol/kg/d), a 19-year-old female was dosed with 1.92 mg of highly enriched C-lutein. Tissues of a nondosed, lutein-fed monkey were used as a reference for natural abundance of C-lutein. On the third day postdose, plasma and multiple tissues were collected. Lutein was quantified by high-performance liquid chromatography-photodiode array detector, and C-lutein tissue enrichment was determined by liquid chromatography quadrupole time-of-flight mass spectrometry. In the tissues of a reference monkey, C-lutein with natural abundance of C-lutein was detectable. In the dosed monkey, highly enriched C-lutein was observed in all analyzed tissues except for the macular and peripheral retina, with the highest concentrations in the liver followed by the adrenal gland and plasma. C-lutein accumulated differentially across 6 brain regions. In adipose depots, C-lutein was observed, with the highest concentrations in the axillary brown adipose tissues. In summary, we evaluated C-lutein tissue distribution in a nonhuman primate following a single dose of isotopically labeled lutein. These results show that tissue distribution 3 days following a dose of lutein varied substantially dependent on tissue type.
尽管人们越来越意识到叶黄素在眼睛和大脑中的作用,但对其在灵长类动物中的药代动力学和组织分布仍知之甚少。我们假设,在单剂量口服后 3 天,C-叶黄素将在成年恒河猴(Macaca mulatta)的组织中呈现出不同的分布。在预先喂食补充了未标记叶黄素(1µmol/kg/d)的饮食一年后,一只 19 岁的雌性猕猴接受了 1.92mg 的高纯度 C-叶黄素的剂量。未接受剂量、喂食叶黄素的猕猴的组织被用作 C-叶黄素自然丰度的参考。在给药后第 3 天,收集了血浆和多个组织。通过高效液相色谱-光电二极管阵列检测器定量叶黄素,通过液相色谱-四极杆飞行时间质谱法测定 C-叶黄素组织富集度。在参考猕猴的组织中,可以检测到具有 C-叶黄素自然丰度的 C-叶黄素。在接受剂量的猕猴中,在除黄斑和周边视网膜以外的所有分析组织中均观察到高纯度的 C-叶黄素,肝脏中的浓度最高,其次是肾上腺和血浆。C-叶黄素在 6 个大脑区域中呈现出不同的积累。在脂肪组织中观察到 C-叶黄素,其浓度最高的部位是腋窝棕色脂肪组织。总之,我们在单剂量同位素标记叶黄素后评估了非人类灵长类动物的 C-叶黄素组织分布。这些结果表明,剂量后 3 天,叶黄素的组织分布在很大程度上取决于组织类型而有所不同。