Circulating mitochondrial biomarkers for drug-induced liver injury.
Liver mitochondria affected by drugs can be released into circulation and serve as biomarkers for drug-induced liver injury (DILI). The tissue specificity of ALT was improved by differentiating cytosolic ALT1 and mitochondrial ALT2 isoforms released in circulation. Prior to ALT elevation, mitochondrial cytochrome c, OCT, GLDH, CPS1 and DNA were increased in circulation following DILI. The baseline expression of mt-Nd6 was predictive of individual DILI susceptibility in animals. As mitochondrial DILI biomarkers appeared to be drug or species dependent, they might have value in clinical scenarios when culprit drugs are established, but may not be ideal tools to assess DILI potentials of new drugs.
Division of Systems Biology, National Center for Toxicological Research, Food & Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Qiang
Q
Shi
Division of Systems Biology, National Center for Toxicological Research, Food & Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Xi
X
Yang
Division of Systems Biology, National Center for Toxicological Research, Food & Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
William B
WB
Mattes
Regulatory Activities, National Center for Toxicological Research, Food & Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Donna L
DL
Mendrick
Department of Environmental & Occupational Health, The University of Arkansas for Medical Sciences, 4301 W Markham St, Little Rock, AR 72205, USA.
Alison H
AH
Harrill
Division of Systems Biology, National Center for Toxicological Research, Food & Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Richard D
RD
Beger
D000818:Animals; D015415:Biomarkers / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D023281:Genomics; D006801:Humans; D055432:Metabolomics; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000097:blood
D015415:Biomarkers; D024101:Mitochondrial Proteins
acetaminophen; biomarker; drug-induced liver injury; hepatotoxicity; mitochondrion