title: Evaluation of miR-122 and other biomarkers in distinct acute liver injury in rats.
abstract: The detection of drug-induced hepatotoxicity remains an important safety issue in drug development. A liver-specific microRNA species, microRNA-122 (miR-122), has recently shown potential for predicting liver injury in addition to the standard hepatic injury biomarkers. The objective of this study was to measure miR-122 together with several other liver markers in distinct settings of acute liver toxicity in rats to determine the value of miR-122 as a biomarker for liver injury in this species. Rats were exposed to 3 well-established liver toxicants (acetaminophen, allyl alcohol, and α-naphthyl isothiocyanate), a liver-enzyme inducer (phenobarbital), or a cardiotoxicant (doxorubicin). There was a clear increase in plasma miR-122 following administration of acetaminophen, allyl alcohol, and α-naphthyl isothiocyanate. The response of miR-122 paralleled that of other markers and was consistent with liver injury as indicated by histopathological evaluation. Furthermore, the changes in miR-122 were detected earlier than standard liver injury markers and exhibited a wide dynamic range. In contrast, miR-122 responses to phenobarbital and doxorubicin were low. Based on these findings, miR-122 shows significant promise and may provide added value for assessing liver toxicity in drug development.
authors.affiliation: Drug Safety Sciences, Janssen Research & Development, A Division of Janssen Pharmaceutica N.V., B-2340 Beerse, Belgium. sstarckx@its.jnj.com
authors.forename: Sofie
authors.initials: S
authors.lastname: Starckx
authors.forename: Ameesha
authors.initials: A
authors.lastname: Batheja
authors.forename: Geert R
authors.initials: GR
authors.lastname: Verheyen
authors.forename: Sandra De
authors.initials: SD
authors.lastname: Jonghe
authors.forename: Kristel
authors.initials: K
authors.lastname: Steemans
authors.forename: Bram Van
authors.initials: BV
authors.lastname: Dijck
authors.forename: Monica
authors.initials: M
authors.lastname: Singer
authors.forename: Nancy
authors.initials: N
authors.lastname: Bogdan
authors.forename: Jan
authors.initials: J
authors.lastname: Snoeys
authors.forename: Petra
authors.initials: P
authors.lastname: Vinken
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Sasaki
authors.forename: Jacky Van
authors.initials: JV
authors.lastname: Gompel
authors.forename: Peggy
authors.initials: P
authors.lastname: Guzzie-Peck
authors.forename: Ann
authors.initials: A
authors.lastname: Lampo
authors.forename: Lieve
authors.initials: L
authors.lastname: Lammens
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000235:genetics / Q000473:pathology; D017953:Isocyanates / Q000633:toxicity; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D009281:Naphthalenes / Q000633:toxicity; D020005:Propanols / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D023382:Toxicity Tests, Acute
chemical_list: D015415:Biomarkers; D017953:Isocyanates; C580643:MIRN122 microRNA, rat; D035683:MicroRNAs; D009281:Naphthalenes; D020005:Propanols; D000082:Acetaminophen; C006463:allyl alcohol; C061621:alpha-naphthyl isocyanate
keywords: ALT; biomarker; hepatotoxicity; liver injury; miR-122; rat.