A longitudinal assessment of miR-122 and GLDH as biomarkers of drug-induced liver injury in the rat

Thulin, Petra, Hornby, Robert J, Auli, Mariona, Nordahl, Gunnar, Antoine, Daniel J, Lewis, Philip Starkey, Goldring, Christopher E, Park, B Kevin ORCID: 0000-0001-8384-824X, Prats, Neus, Glinghammar, Bjorn
et al (show 1 more authors) (2017) A longitudinal assessment of miR-122 and GLDH as biomarkers of drug-induced liver injury in the rat. BIOMARKERS, 22 (5). pp. 461-469.

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<h4>Context</h4>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.<h4>Objective</h4>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).<h4>Materials and methods</h4>qRT-PCR and a standard enzymatic assay were used for biomarker analysis.<h4>Results</h4>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.<h4>Discussion and conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: Hepatotoxicity, acetaminophen, exosomes, ALT, GLDH, miR-122
Depositing User: Symplectic Admin
Date Deposited: 08 Jan 2018 09:46
Last Modified: 19 Jan 2023 07:24
DOI: 10.1080/1354750X.2016.1269131
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3005025