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单次口服后,C-叶黄素在成年雌性恒河猴组织中的分布存在差异:一项初步研究。

C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study.

机构信息

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.

出版信息

Nutr Res. 2019 Jan;61:102-108. doi: 10.1016/j.nutres.2018.10.007. Epub 2018 Oct 28.

Abstract

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.

摘要

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。

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