Article

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

ABSTRACT

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.

Download full-text

Full-text

Available from: Shashi Bala
  • Source
    • "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) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Acetaminophen (APAP) is a commonly used analgesic drug that can cause liver injury, liver necrosis and liver failure. APAP-induced liver injury is associated with glutathione depletion, the formation of APAP protein adducts, the generation of reactive oxygen and nitrogen species and mitochondrial injury. The systems biology omics technologies (transcriptomics, proteomics and metabolomics) have been used to discover potential translational biomarkers of liver injury. The following review provides a summary of the systems biology discovery process, analytical validation of biomarkers and translation of omics biomarkers from the nonclinical to clinical setting in APAP-induced liver injury.
    Full-text · Article · May 2015 · Archives of Toxicology
    • "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) "

    No preview · Article · Sep 2014 · Toxicology Letters
  • Source
    • "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) "
    [Show abstract] [Hide abstract]
    ABSTRACT: MiRNAs (microRNAs) are single-stranded non-coding RNAs of approximately 21-23 nucleotides in length whose main function is to inhibit gene expression by interfering with mRNA processes. MicroRNAs suppress gene expression by affecting mRNA (messenger RNAs) stability, targeting the mRNA for degradation, or both. In this review, we have examined how microRNA expression could be altered following exposure to chemicals and how they could represent appropriate tissue and more interestingly circulating biomarkers. Among the key questions before using the microRNA for evaluation of risk toxicity, it remains still to clarify how they could be causally involved in the adverse effects and how stable their changes are.
    Full-text · Article · Jan 2014 · Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
Show more