Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 14, 2012; 18(22): 2798-2804
Published online Jun 14, 2012. doi: 10.3748/wjg.v18.i22.2798
Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study
Jeanine Ward, Shashi Bala, Jan Petrasek, Gyongyi Szabo
Jeanine Ward, Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, United States
Shashi Bala, Jan Petrasek, Gyongyi Szabo, Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01655, United States
Author contributions: Ward J and Szabo G contributed to the research concept, experimental design, data analysis and drafting of the manuscript; Bala S carried out the data analyses and drafting of the manuscript; Petrasek J contributed to the experimental design and performed the statistical analysis; all authors read and approved the final manuscript.
Supported by PHS grant DK075635 to Szabo G and McNeil Consumer Healthcare, a division of McNeil-PCC Inc. to Ward J
Correspondence to: Gyongyi Szabo, MD, PhD, Professor, Vice Chair for Research, Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01655, United States. gyongyi.szabo@umassmed.edu
Telephone: +1-508-8565275 Fax: +1-508-8564770
Received: July 28, 2011
Revised: September 4, 2011
Accepted: April 12, 2012
Published online: June 14, 2012
Abstract

AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice.

METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters.

RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011).

CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.

Keywords: Plasma microRNA; Hepatotoxicity; Acetaminophen; Drug-induced liver injury; Alanine aminotransferase