Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: a research study.
OBJECTIVE
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 574-5 p, 466 g, 466 f-3p, 375, 29 c, and 148 a, 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).


CONCLUSIONS
We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.
Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, United States.
Jeanine
J
Ward
Shashi
S
Bala
Jan
J
Petrasek
Gyongyi
G
Szabo
D000082:Acetaminophen; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood*; D020411:Oligonucleotide Array Sequence Analysis
D005819:Genetic Markers; D035683:MicroRNAs; D000082:Acetaminophen; D000410:Alanine Transaminase