Urinary Micrornas as Noninvasive Biomarkers for Acetaminophen- Induced Liver InjuryXi Yang1, Zhiguang Li2, Zhenqiang Su3, Kelly Davis4, Tao Chen2, Donna L Mendrick1 and William Salminen1*
- *Corresponding Author:
- Dr. William Salminen
Division of Systems Biology
National Center for Toxicological Research
Food and Drug Administration
3900 NCTR Road, Jefferson, AR 72079, USA
E-mail: [email protected]
Received date: March 02, 2011; Accepted date: April 06, 2011; Published date: April 08, 2011
Citation: Yang X, Li Z, Su Z, Davis K, Chen T, et al. (2011) Urinary Micrornas as Noninvasive Biomarkers for Acetaminophen-Induced Liver Injury. J Postgenom Drug Biomark Develop 1:101. doi:10.4172/2153-0769.1000101
Copyright: © 2011 Yang X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.