Escaron Anne L, Tanumihardjo Sherry A
University of Wisconsin-Madison, USA.
Comp Med. 2010 Feb;60(1):71-6.
The mechanism responsible for the metabolism of vitamin A during hypervitaminosis is largely unknown. This study investigated hepatic (13)C-retinol uptake in hypervitaminotic A rhesus monkeys. We hypothesized that individual retinyl esters would be enriched in (13)C after a physiologic dose of (13)C(2)-retinyl acetate, thus suggesting de novo in vivo hepatic retinol esterification. Male rhesus macaques (n = 16; 11.8 +/- 2.9 y) each received 3.5 micromol 14, 15-(13)C(2)-retinyl acetate. Blood was drawn at baseline and 5 h and 2, 4, 7, 14, 21, and 28 d after administration. Liver biopsies were collected 7 d before and 2 d after dose administration (n = 4) and at 7, 14, and 28 d after dose administration (n = 4 per time point). (13)C enrichments of retinol and retinyl esters HPLC-purified from liver samples were measured by using gas chromatography-combustion-isotope ratio mass spectrometry. (13)C enrichment of total vitamin A and individual retinyl esters were significantly greater 2 d after dose administration compared with baseline levels. In contrast, the concentration of isolated retinyl esters did not always increase 2 d after treatment. Given that the liver biopsy site differed between monkeys, these data suggest that the accumulation of hepatic retinyl esters is a dynamic process that is better represented by combining analytical techniques. This sensitive methodology can be used to characterize vitamin A trafficking after physiologic doses of (13)C-retinol. In this nonhuman primate model of hypervitaminosis A, hepatic retinyl esters continued to accumulate with high liver stores.
维生素A过多症期间维生素A代谢的机制在很大程度上尚不清楚。本研究调查了维生素A过多的恒河猴肝脏对（13）C - 视黄醇的摄取情况。我们假设，在给予生理剂量的（13）C（2） - 醋酸视黄酯后，各个视黄酯的（13）C会富集，从而表明体内肝脏存在从头合成视黄醇酯化作用。雄性恒河猴（n = 16；11.8±2.9岁）每只接受3.5微摩尔14,15 - （13）C（2） - 醋酸视黄酯。在给药前的基线、给药后5小时以及2、4、7、14、21和28天采集血液。在给药前7天和给药后2天（n = 4）以及给药后7、14和28天（每个时间点n = 4）采集肝脏活检样本。通过气相色谱 - 燃烧 - 同位素比率质谱法测量从肝脏样本中经HPLC纯化的视黄醇和视黄酯的（13）C富集情况。与基线水平相比，给药后2天总维生素A和各个视黄酯的（13）C富集显著更高。相比之下，分离的视黄酯浓度在治疗后2天并不总是增加。鉴于猴子之间肝脏活检部位不同，这些数据表明肝脏视黄酯的积累是一个动态过程，通过结合分析技术能更好地体现。这种灵敏的方法可用于表征生理剂量的（13）C - 视黄醇后维生素A的转运情况。在这个维生素A过多症的非人类灵长类动物模型中，肝脏视黄酯持续积累，肝脏储存量很高。
