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Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia.对缺铁婴儿猴的多组学分析揭示了贫血发生前血清和脑脊液中与神经有关的重要生化物质的改变。
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用右旋糖酐铁纠正缺铁性贫血会改变恒河猴婴儿的血清代谢组学特征。

Correcting iron deficiency anemia with iron dextran alters the serum metabolomic profile of the infant Rhesus Monkey.

机构信息

Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.

Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN, USA.

出版信息

Am J Clin Nutr. 2021 Apr 6;113(4):915-923. doi: 10.1093/ajcn/nqaa393.

DOI:10.1093/ajcn/nqaa393
PMID:33740040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8023818/
Abstract

BACKGROUND

The effects of infantile iron deficiency anemia (IDA) extend beyond hematological indices and include short- and long-term adverse effects on multiple cells and tissues. IDA is associated with an abnormal serum metabolomic profile, characterized by altered hepatic metabolism, lowered NAD flux, increased nucleoside levels, and a reduction in circulating dopamine levels.

OBJECTIVES

The objective of this study was to determine whether the serum metabolomic profile is normalized after rapid correction of IDA using iron dextran injections.

METHODS

Blood was collected from iron-sufficient (IS; n = 10) and IDA (n = 12) rhesus infants at 6 months of age. IDA infants were then administered iron dextran and vitamin B via intramuscular injections at weekly intervals for 2 to 8 weeks. Their hematological and metabolomic statuses were evaluated following treatment and compared with baseline and a separate group of age-matched IS infants (n = 5).

RESULTS

Serum metabolomic profiles assessed at baseline and after treatment via HPLC/MS using isobaric standards identified 654 quantifiable metabolites. At baseline, 53 metabolites differed between IS and IDA infants. Iron treatment restored traditional hematological indices, including hemoglobin and mean corpuscular volume, into the normal range, but the metabolite profile in the IDA group after iron treatment was markedly altered, with 323 metabolites differentially expressed when compared with an infant's own baseline profile.

CONCLUSIONS

Rapid correction of IDA with iron dextran resulted in extensive metabolic changes across biochemical pathways indexing the liver function, bile acid release, essential fatty acid production, nucleoside release, and several neurologically important metabolites. The results highlight the importance of a cautious approach when developing a route and regimen of iron repletion to treat infantile IDA.

摘要

背景

婴儿缺铁性贫血(IDA)的影响不仅局限于血液学指标,还包括对多种细胞和组织的短期和长期不良影响。IDA 与异常的血清代谢组学特征相关,其特征为肝代谢异常、NAD 通量降低、核苷水平升高以及循环多巴胺水平降低。

目的

本研究旨在确定使用右旋糖酐铁注射快速纠正 IDA 后,其血清代谢组学特征是否恢复正常。

方法

在 6 月龄时,采集铁充足(IS;n=10)和 IDA(n=12)恒河猴婴儿的血液。然后,IDA 婴儿每周接受肌内注射右旋糖酐铁和维生素 B,持续 2 至 8 周。在治疗后评估其血液学和代谢状态,并与基线和另一组年龄匹配的 IS 婴儿(n=5)进行比较。

结果

通过高效液相色谱/质谱法(HPLC/MS)使用等压标准品评估的基线和治疗后的血清代谢组学图谱共鉴定出 654 种可定量的代谢物。基线时,IS 和 IDA 婴儿之间有 53 种代谢物存在差异。铁治疗将传统的血液学指标(包括血红蛋白和平均红细胞体积)恢复到正常范围,但 IDA 组在铁治疗后的代谢谱明显改变,与婴儿自身的基线谱相比,有 323 种代谢物存在差异表达。

结论

用右旋糖酐铁快速纠正 IDA 会导致涉及肝功能、胆汁酸释放、必需脂肪酸生成、核苷释放以及几种神经重要代谢物的生化途径的广泛代谢变化。研究结果强调了在开发治疗婴儿 IDA 的铁补充途径和方案时,应谨慎行事。