Evaluation of miR-122 and other biomarkers in distinct acute liver injury in rats

Starckx S, Batheja A, Verheyen GR, Jonghe SD, Steemans K, Dijck BV, Singer M, Bogdan N, Snoeys J, Vinken P, Sasaki JC, Gompel JV, Guzzie-Peck P, Lampo A, Lammens L.
Journal   Toxicol Pathol.
Analytes Measured  
Matrix Tested   Serum
Year   2012
Page Numbers  
Application   Toxicology
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.

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