Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study

Department of Emergency Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, United States.
World Journal of Gastroenterology (Impact Factor: 2.37). 06/2012; 18(22):2798-804. DOI: 10.3748/wjg.v18.i22.2798
Source: PubMed


To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice.
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.
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).
We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.

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Available from: Shashi Bala,
    • "Realtime polymerase chain reaction (qPCR) and microarrays are the two well-established miRNA-profiling approaches for miRNA detection; next-generation sequencing (NGS) is another new method based on direct sequencing. The qPCR platform provides a larger dynamic range of miRNA detection and therefore requires less sample volume and Table 1 Translational microRNA biomarkers of acetaminophen liver injury a Plasma miR-122 down-regulation at the 12-h time point of this study b 22 subjects with ALT elevations exceeding 3 × baselines ALT compared to 22 matched patients without ALT c (Wang et al. 2009) d (Starkey Lewis et al. 2011) e (Bala et al. 2012) f (Antoine et al. 2013) g (Su et al. 2012) h (Thulin et al. 2014) i (Ward et al. 2012) j (Ward et al. 2014) k (Yamaura et al. 2012) l (Krauskopf et al. 2015) m (Starckx et al. 2013) "

    Toxicology Letters 09/2014; 229:S99-S100. DOI:10.1016/j.toxlet.2014.06.367 · 3.26 Impact Factor
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    • "Acetaminophen, allyl alcohol, and ␣-naphthyl isothiocyanate Liver Rat miR-122 [124] 2,3,7,8-tetrachlorodibenzo-p-dioxin (environmental contaminant) Thymus Mouse miR-122 and miR-181a miR-23a, miR-18b, miR-31 miR-182 [125] 2,3,7,8-tetrachlorodibenzo-p-dioxin Embryo Zebrafish miR-27e [126] Doxorubicin Heart Mouse 208b, miR-216b, miR-215, miR-34c and miR-367 [127] Cyanobacterial hepatotoxin microcystin-LR Whitefish let-7c, miR-9b), (miR-16a, miR-21a, miR-34a) (miR-122) [128] Ethanol Liver Rat Mir-21 [129] Printex 90 carbon black nanoparticles Lung Mouse miR-135b [130] Arsenic Umbilical endothelial cell Human [128] Arsenic Liver Mouse [131] Acetaminophen Liver Mouse 74-5p, 135a*, 466g, 1196, 466f-3p, 877, 342-3p, 195, 375, 29c, 148a, 652 [132] Gentamicin Kidney Mouse Mir-21, 155 [133] 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (carcinogen from cooked meat) "
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