Escaron Anne L, Green Michael H, Howe Julie A, Tanumihardjo Sherry A
Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin, Madison, WI 53706, USA.
J Nutr. 2009 Oct;139(10):2000-6. doi: 10.3945/jn.109.111922. Epub 2009 Aug 26.
Hypervitaminosis A is increasingly a public health concern, and thus noninvasive quantitative methods merit exploration. In this study, we applied the (13)C-retinol isotope dilution test to a nonhuman primate model with excessive liver stores. After baseline serum chemistries, rhesus macaques (Macaca mulatta; n = 16) were administered 3.5 mumol (13)C(2)-retinyl acetate. Blood was drawn at baseline, 5 h, and 2, 4, 7, 14, 21, and 28 d following the dose. Liver biopsies were collected 7 d before and 2 d after dosing (n = 4) and at 7, 14, and 28 d (n = 4/time) after dosing. Serum and liver were analyzed by HPLC and GC-combustion-isotope ratio MS for retinol and its enrichment, respectively. Model-based compartmental analysis was applied to serum data. Lactate dehydrogenase was elevated in 50% of the monkeys. Total body reserves (TBR) of vitamin A (VA) were calculated at 28 d. Predicted TBR (3.52 +/- 2.01 mmol VA) represented measured liver stores (4.56 +/- 1.38 mmol VA; P = 0.124). Predicted liver VA concentrations (13.3 +/- 9.7 micromol/g) were similar to measured liver VA concentrations (16.4 +/- 5.3 micromol/g). The kinetic models predict that 27-52% of extravascular VA is exchanging with serum in hypervitaminotic A monkeys. The test correctly diagnosed hypervitaminosis A in all monkeys, i.e. 100% sensitivity. Stable isotope techniques have important public health potential for the classification of VA status, including hypervitaminosis, because no other technique besides invasive liver biopsies, correctly identifies excessive liver VA stores.
维生素A过多症日益成为一个公共卫生问题，因此非侵入性定量方法值得探索。在本研究中，我们将（13）C-视黄醇同位素稀释试验应用于肝脏储存过量的非人灵长类动物模型。在测定基线血清化学指标后，给恒河猴（猕猴属；n = 16）静脉注射3.5 μmol（13）C2-视黄醇醋酸酯。在给药前的基线、给药后5小时以及给药后的2、4、7、14、21和28天采集血液样本。在给药前7天和给药后2天（n = 4）以及给药后7、14和28天（每次n = 4）采集肝脏活检样本。分别通过高效液相色谱法（HPLC）和气相色谱-燃烧-同位素比率质谱法（GC-燃烧-IRMS）分析血清和肝脏中的视黄醇及其富集情况。将基于模型的房室分析应用于血清数据。50%的猴子乳酸脱氢酶升高。在第28天计算维生素A（VA）的全身储备（TBR）。预测的TBR（3.52±2.01 mmol VA）与实测的肝脏储存量（4.56±1.38 mmol VA；P = 0.124）相符。预测的肝脏VA浓度（13.3±9.7 μmol/g）与实测的肝脏VA浓度（16.4±5.3 μmol/g）相似。动力学模型预测，在维生素A过多的猴子中，27%-52%的血管外VA与血清进行交换。该试验在所有猴子中均正确诊断出维生素A过多症，即灵敏度为100%。稳定同位素技术在VA状态分类（包括维生素A过多症）方面具有重要的公共卫生潜力，因为除了侵入性肝脏活检外，没有其他技术能够正确识别肝脏中过量的VA储存。
