Urinary Micrornas as Noninvasive Biomarkers for Acetaminophen-Induced Liver Injury
Urinary Micrornas as Noninvasive Biomarkers for Acetaminophen-Induced Liver Injury
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尿微RNA作为对乙酰氨基酚引起的肝损伤的非侵入性生物标志物
DOI：
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
W. Salminen
中科院分区：
文献类型：
--
作者：
Xi Yang;Zhiguang Li;Z. Su;K. Davis;Tao Chen;D. Mendrick;W. Salminen
最近的几项研究测量了毒素诱导的肝损伤后循环血浆microRNA（miRNAs）水平的升高，这很可能是由于受损肝细胞的渗漏。在尿液中也检测到了miRNAs，其中一些来自泌尿系统以外的器官，开辟了它们作为疾病或损伤的非侵入性生物标志物的潜在用途。尽管存在这种可能性，但尚未将尿miRNA谱的变化作为药物诱导的肝损伤的生物标志物进行研究。在这项研究中，从单次口服剂量的对乙酰氨基酚（APAP：100或1250 mg/kg）治疗的大鼠中评估尿液miRNA谱。低剂量未引起指示肝损伤的任何临床病理学或组织病理学变化。相比之下，高剂量增加了24小时肝损伤的临床病理学和组织病理学指数;然而，这些终点的动物间变异性较高。在任一APAP剂量下均未观察到肾损伤的证据。尿miRNA水平与肝小叶中心糖原耗竭程度相关性最好。与血清丙氨酸和天冬氨酸转氨酶和小叶中心肝坏死的高动物间变异性相反，所有高剂量动物的尿miRNA水平均持续升高。在低剂量动物中也观察到尿miRNA谱的改变，尽管数量较少。这些结果表明，尿液中的特异性miRNA可以反映APAP诱导的肝损伤的严重程度，因此有可能用作非侵入性临床前和临床生物标志物。
Several recent studies measured elevated levels of circulating plasma microRNAs (miRNAs) after toxicant-induced liver injury, most likely due to leakage from damaged hepatocytes. miRNAs have also been detected in urine with some of them being derived from organs outside of the urinary system, opening up their potential use as noninvasive biomarkers of disease or injury. Despite this potential, changes in urine miRNA profiles have not been investigated as biomarkers for drug-induced liver injury. In this study, urine miRNA profiles were assessed from rats treated with a single oral dose of acetaminophen (APAP: 100 or 1250 mg/kg). The low dose did not cause any clinical pathology or histopathological changes indicative of liver injury. In contrast, the high dose increased clinical pathology and histopathological indices of liver injury at 24 hours; however, there was a high inter-animal variability in these endpoints. No evidence of kidney injury was noted at either APAP dose. Urinary miRNA levels correlated best with the degree of liver centrilobular glycogen depletion. In contrast to the high inter-animal variability noted for serum alanine and aspartate aminotransferases and centrilobular liver necrosis, urinary miRNA levels were consistently elevated in all high dose animals. Alterations in the urinary miRNA profiles were also noted in the low dose animals, albeit fewer in number. These results suggest that specific miRNAs in the urine could reflect the severity of APAP-induced liver injury and therefore have the potential to be used as noninvasive preclinical and clinical biomarkers.
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影响因子：
3.8
作者：
Newton,JF;Bailie,MB;Hook,JB
通讯作者：
Hook,JB
影响因子：
--
作者：
Hinson, Jack A;Roberts, Dean W;James, Laura P
通讯作者：
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影响因子：
4.5
作者：
Bail, Sophie;Swerdel, Mavis;Kiledjian, Megerditch
通讯作者：
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DOI：
10.1016/bs.apha.2019.02.001
发表时间：
2019-01-01
期刊：
Advances in pharmacology (San Diego, Calif.)
影响因子：
--
作者：
McGill, Mitchell R;Jaeschke, Hartmut
通讯作者：
Jaeschke, Hartmut
影响因子：
3.8
作者：
Heinloth, AN;Irwin, RD;Paules, RS
通讯作者：
Paules, RS