ASSESSING HIGH DIETARY VITAMIN A

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 目的：进一步明确长期高维生素A饮食的影响。 最近的工作检查维生素A（VA）状态的恒河猴（猕猴）作为人类生物医学研究的模型显示亚毒性肝脏VA浓度。他们食用的普通研究饮食提供的VA量是NRC推荐的四倍。 为了进一步确定恒河猴中的VA状态，使用雄性恒河猴进行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了“异常”乳酸脱氢酶值。 LDH的升高是引起关注的原因，因为它是肝脏疾病或功能障碍的标志，这是维生素A毒性的直接结果。 此外，由于致畸问题，妊娠期间禁忌过量摄入预制VA。 为了研究预先形成的VA对早期胎肝VA储存的过度消耗，分析了胎龄为35至93天的猴胎肝的VA（n = 19）和视黄酸（n = 9）。 在所有胎儿肝脏中均发现了视黄酯，且视黄醇在年轻胎儿中的百分比更明显。 肝脏VA浓度随胎龄增加（r = 0.98，P 0.0001），最年轻（35 d）和最年长（93 d）胎儿的范围分别为0.0011 - 0.26 μ mol/g。 妊娠早期和妊娠中期胎儿的肝脏VA浓度分别为0.023 <$0.008 <$mol/g和0.19 <$0.06 <$mol/g。 妊娠早期的全反式维甲酸浓度（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。 妊娠中期胎仔的肝脏VA浓度高于发育后期胎仔和猴肝脏中观察到的浓度，此时假定生长和VA蓄积率最高。 因此，母亲过量摄入预先形成的VA会导致早期胎肝视黄酯储存放大。 这项研究使用WNPRC研究服务。 出版物： Dever JT，Tanumihardjo SA.实验性非人灵长类动物维生素A过多症：证据，原因和恢复之路。《美国医学杂志》2009年10月;71（10）：813-6。

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.