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.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 目的：进一步定义了慢性饮食维生素A的影响。 最近研究的恒河猴（Macaca mulatta）用作人类生物医学研究模型的恒河猴A（VA）状态的最新工作显示，肝含量无毒性的VA浓度。他们食用的常见研究饮食可提供NRC推荐的VA量的四倍。为了进一步定义恒河猴中的VA状态，将雄性恒河猴用于涉及稳定同位素和肝活检的研究。我们在16位男性恒河猴中的8个（11.9€2.9 y）中发现了化学筛选谱的“异常”乳酸脱氢酶值。 LDH的升高引起了人们的关注，因为它是肝病或故障的标志，这是维生素A毒性的直接结果。此外，由于致病性问题，在怀孕期间禁忌过多的VA摄入量。为了研究早期胎儿肝VA储存中预先形成的VA的过度消费，分析了VA（n = 19）和视黄酸（n = 9）的猴子胎儿肝脏的35至93 d胎龄。在所有胎儿生活中都鉴定出视网膜酯，而视黄醇（百分比）在年轻的胎儿中更为明显。肝脏VA浓度随胎龄的增加（r = 0.98，p 0.0001），最小（35 d）和最古老的胎儿（93 d）分别为0.0011至0.26»mol/g。肝脏VA浓度为0.023€0.008？/g在妊娠期，妊娠中期胎儿中的摩尔/g 0.19€0.06？/g。早期妊娠（99.2€57.0 pmol/g，n = 6）中，全反式视黄酸浓度高于妊娠中期（18.2€6.1 pmol/g，n = 3），但可变。妊娠中期胎儿的肝脏VA浓度高于胎儿人类和猴子在发育后期的生活，当时生长和VA积累率最高。这是母亲对预先形成的VA的过多摄入会导致早期胎儿肝视网膜酯储存。 这项研究使用了WNPRC研究服务。 发布： Dever JT，Tanumihardjo SA。实验非人类灵长类动物中的高vitaminiso A：证据，原因和恢复道路。 Am J Primatol。 2009年10月； 71（10）：813-6。