%0 Journal Article
%T A longitudinal assessment of miR-122 and GLDH as biomarkers of drug-induced liver injury in the rat.
%A Thulin P
%A Hornby RJ
%A Auli M
%A Nordahl G
%A Antoine DJ
%A Starkey Lewis P
%A Goldring CE
%A Park BK
%A Prats N
%A Glinghammar B
%A Schuppe-Koistinen I
%J Biomarkers
%V 22
%N 5
%D Jul 2017
%M 27978773
%F 2.663
%R 10.1080/1354750X.2016.1269131
%X <B>BACKGROUND: </B>There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, and translational biomarker of DILI in both rodent, and human studies.<BR><B>OBJECTIVE: </B>To build on previous work within the field, we examined biomarker kinetics in a rat model of acetaminophen (APAP)-induced liver injury to confirm the sensitivity, and specificity of miR-122 and glutamate dehydrogenase (GLDH).<BR><B>METHODS: </B>qRT-PCR and a standard enzymatic assay were used for biomarker analysis.<BR><B>RESULTS: </B>Both miR-122 and GLDH were demonstrated to be more readily-detectable biomarkers of APAP-DILI than alanine aminotransferase (ALT). Peak levels for all biomarkers were detected at 2 days after APAP. At day 3, miR-122 had returned to baseline; however, other biomarkers remained elevated between 3 and 4 days. We were also able to demonstrate that, although miR-122 is present in greater quantities in exosome-free form, both exosome-bound and non-vesicle bound miR-122 are released in a similar profile throughout the course of DILI.<BR><B>CONCLUSIONS: </B>Together, this study demonstrates that both GLDH and miR-122 could be used during preclinical drug-development as complementary biomarkers to ALT to increase the chance of early detection of hepatotoxicity.