title: Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis.
abstract: We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.
authors.affiliation: University of Massachusetts Memorial Medical Center, Worcester, MA 01605;
authors.forename: Jeanine
authors.initials: J
authors.lastname: Ward
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605;
authors.forename: Chitra
authors.initials: C
authors.lastname: Kanchagar
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605;
authors.forename: Isana
authors.initials: I
authors.lastname: Veksler-Lublinsky
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605;
authors.forename: Rosalind C
authors.initials: RC
authors.lastname: Lee
authors.affiliation: University of Kansas Medical Center, Kansas City, KS 66160; and.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: McGill
authors.affiliation: University of Kansas Medical Center, Kansas City, KS 66160; and.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Jaeschke
authors.affiliation: Banner Good Samaritan Medical Center; University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85006.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Curry
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605; victor.ambros@umassmed.edu.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Ambros
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D006505:Hepatitis / Q000097:blood* / Q000150:complications; D006801:Humans; D007511:Ischemia / Q000097:blood*; D035683:MicroRNAs / Q000097:blood*; D011041:Poisoning / Q000097:blood / Q000188:drug therapy; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D000082:Acetaminophen; D000410:Alanine Transaminase; D000111:Acetylcysteine
keywords: hsa-miR-122-5p; hsa-miR-3646-3p; hsa-miR-412
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