Potential of extracellular microRNAs as biomarkers of acetaminophen toxicity in children.
Potential of extracellular microRNAs as biomarkers of acetaminophen toxicity in children.
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DOI：
10.1016/j.taap.2015.02.013
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发表时间：
2015-04-15
影响因子：
3.8
通讯作者：
James LP
中科院分区：
文献类型：
--
作者：
Yang X;Salminen WF;Shi Q;Greenhaw J;Gill PS;Bhattacharyya S;Beger RD;Mendrick DL;Mattes WB;James LP
开发用于检测对乙酰氨基酚（APAP）毒性的生物标志物已被广泛研究。最近对APAP诱导的肝损伤成人的研究报告了人血清microRNA-122（miR-122）作为APAP诱导的肝损伤的新生物标志物。本研究的目的是检查细胞外microRNAs（miRNAs）作为儿童APAP肝损伤的潜在生物标志物。在三个儿科亚组中检查了血清和尿液miRNA的总体水平：1）健康儿童（n=10），2）接受治疗剂量的APAP的住院儿童（n=10）和3）因APAP过量而住院的儿童（n=8）。在APAP过量组检测到的147种miRNA中，有8种在血清中的中位数水平（miR-122，−375，−423- 5 p，− 30 d-5 p，− 125 b-5 p，−4732- 5 p，−204- 5 p和−574- 3 p）与其他组相比显着增加。与其他组相比，来自相同患者的尿液样本分析显著增加了四种miRNA（miR-375，−940，−9- 3 p和− 302 a）的中位数水平。重要的是，峰值血清APAP蛋白加合物水平（APAP氧化为反应性代谢物N-乙酰基对苯醌亚胺的指标）与峰值miRNA水平的相关性显示，观察到血清miR-122（R=0.94; p<0.01）的相关性最高，其次是miR-375（R=0.70; p=0.05）。结论：我们的研究结果表明，在APAP毒性儿童中，miRNAs增加，并与APAP蛋白加合物相关，这表明作为APAP毒性生物标志物的潜在作用。
Developing biomarkers for detecting acetaminophen (APAP) toxicity has been widely investigated. Recent studies of adults with APAP-induced liver injury have reported human serum microRNA-122 (miR-122) as a novel biomarker of APAP-induced liver injury. The goal of this study was to examine extracellular microRNAs (miRNAs) as potential biomarkers for APAP liver injury in children. Global levels of serum and urine miRNAs were examined in three pediatric subgroups: 1) healthy children (n=10), 2) hospitalized children receiving therapeutic doses of APAP (n=10) and 3) children hospitalized for APAP overdose (n=8). Out of 147 miRNAs detected in the APAP overdose group, eight showed significantly increased median levels in serum (miR-122, −375, −423-5p, −30d-5p, −125b-5p, −4732-5p, −204-5p, and −574-3p), compared to the other groups. Analysis of urine samples from the same patients had significantly increased median levels of four miRNAs (miR-375, −940, −9-3p and −302a) compared to the other groups. Importantly, correlation of peak serum APAP protein adduct levels (an indicator of the oxidation of APAP to the reactive metabolite N-acetylpara-quinone imine) with peak miRNA levels showed that the highest correlation was observed for serum miR-122 (R=0.94; p<0.01) followed by miR-375 (R=0.70; p=0.05). Conclusion: Our findings demonstrate that miRNAs are increased in children with APAP toxicity and correlate with APAP protein adducts, suggesting a potential role as biomarkers of APAP toxicity.