ASSESSING HIGH DIETARY VITAMIN A

评估高膳食维生素 A

• 批准号: 8173070
• 负责人: SHERRY A TANUMIHARDJO
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173070
• 关键词: All-Trans-Retinol; Biomedical Research; Chemistry; Computer Retrieval of Information on Scientific Projects Database; Development; Diet Research; Esters; Fetal Liver; Fetus; Funding; Gestational Age; Grant; Growth; Hepatic; Human; Hypervitaminosis A; Institution; Intake; Lactate Dehydrogenase; Liver; Liver diseases; Macaca mulatta; Modeling; Monkeys; Mothers; Outcome; Pregnancy; Publications; Recovery; Research; Research Personnel; Resources; Screening procedure; Services; Source; Staging; Time; Toxic effect; Tretinoin; United States National Institutes of Health; Vitamin A; Vitamins; Work; fetal; liver biopsy; male; nonhuman primate; stable isotope

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To further define the effects of chronically high dietary vitamin A. Recent work examining the vitamin A (VA) status of rhesus monkeys (Macaca mulatta) used as models for human biomedical research revealed subtoxic hepatic VA concentrations. They consume common research diets that provide up to four times the amount of VA recommended by the NRC. To further define VA status in rhesus monkeys, male rhesus monkeys were used for a study that involved stable isotopes and liver biopsies. We found "abnormal" lactate dehydrogenase values in the chemistry screening profiles in 8 of the 16 male rhesus monkeys (11.9 ¿ 2.9 y). Elevation of LDH is cause for concern as it is a marker of liver disease or malfunction, which is a direct outcome of vitamin A toxicity. Furthermore, excessive preformed VA intake is contraindicated during pregnancy due to teratogenic concerns. To investigate overconsumption of preformed VA on early fetal liver VA storage, monkey fetal livers ranging from 35 to 93 d gestational age were analyzed for VA (n = 19) and retinoic acid (n = 9). Retinyl esters were identified in all fetal livers, and retinol, as a percentage, was more pronounced in younger fetuses. Liver VA concentration increased with gestational age (r = 0.98, P 0.0001), ranging from 0.0011 to 0.26 ¿mol/g in the youngest (35 d) and oldest fetuses (93 d), respectively. Liver VA concentrations were 0.023 ¿ 0.008 ¿mol/g in early gestation and 0.19 ¿ 0.06 ¿mol/g in mid-gestation fetuses. All-trans retinoic acid concentrations were higher in early gestation (99.2 ¿ 57.0 pmol/g, n = 6) than in mid-gestation (18.2 ¿ 6.1 pmol/g, n = 3), but were variable. Liver VA concentrations from mid-gestation fetuses were higher than those observed in fetal human and monkey livers from later stages of development, when growth and VA accumulation rates are assumed to be highest. Thus, excessive intake of preformed VA by the mothers results in amplified early fetal liver retinyl ester storage. This research used WNPRC Research Services. PUBLICATION: Dever JT, Tanumihardjo SA. Hypervitaminosis A in experimental nonhuman primates: evidence, causes, and the road to recovery. Am J Primatol. 2009 Oct;71(10):813-6.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目的：进一步明确长期高膳食维生素 A 的影响。 最近对用作人类生物医学研究模型的恒河猴 (Macaca mulatta) 的维生素 A (VA) 状态进行了检查，结果发现肝脏 VA 浓度处于低毒性。他们食用常见的研究饮食，所提供的维生素A含量是NRC建议的四倍。 为了进一步确定恒河猴的 VA 状态，使用雄性恒河猴进行了一项涉及稳定同位素和肝活检的研究。 我们在 16 只雄性恒河猴中的 8 只（11.9 ¿ 2.9 岁）的化学筛选曲线中发现“异常”乳酸脱氢酶值。 LDH 升高引起人们的关注，因为它是肝脏疾病或功能障碍的标志，而肝脏疾病或功能障碍是维生素 A 中毒的直接结果。 此外，由于存在致畸问题，怀孕期间禁止过量摄入 VA。 为了调查早期胎儿肝脏 VA 储存中预先形成的 VA 的过度消耗，对胎龄 35 至 93 天的猴胎儿肝脏进行了 VA (n = 19) 和视黄酸 (n = 9) 的分析。 在所有胎儿肝脏中均发现了视黄酯，而视黄醇的百分比在较年轻的胎儿中更为明显。 肝脏 VA 浓度随胎龄增加而增加（r = 0.98，P < 0.0001），最小胎儿（35 天）和最大胎儿（93 天）的范围分别为 0.0011 至 0.26 µmol/g。 妊娠早期胎儿肝脏 VA 浓度为 0.023 ¡ 0.008 ¡ mol/g，妊娠中期胎儿肝脏 VA 浓度为 0.19 ¡ 0.06 ¡ mol/g。 妊娠早期的全反式视黄酸浓度（99.2 × 57.0 pmol/g，n = 6）高于妊娠中期（18.2 × 6.1 pmol/g，n = 3），但存在差异。 妊娠中期胎儿的肝脏 VA 浓度高于在发育后期的人类胎儿和猴肝脏中观察到的浓度，此时生长和 VA 积累率被认为是最高的。 因此，母亲过量摄入预先形成的 VA 会导致早期胎儿肝脏视黄酯储存量增加。 本研究使用了 WNPRC 研究服务。 发布： Dever JT，Tanumihardjo SA。实验性非人灵长类动物维生素 A 过多症：证据、原因和康复之路。我是 J Primatol。 2009 年 10 月；71(10):813-6。