RGD Reference Report - Identification of novel liver-specific mRNAs in plasma for biomarkers of drug-induced liver injury and quantitative evaluation in rats treated with various hepatotoxic compounds. - Rat Genome Database

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Identification of novel liver-specific mRNAs in plasma for biomarkers of drug-induced liver injury and quantitative evaluation in rats treated with various hepatotoxic compounds.

Authors: Okubo, S  Miyamoto, M  Takami, K  Kanki, M  Ono, A  Nakatsu, N  Yamada, H  Ohno, Y  Urushidani, T 
Citation: Okubo S, etal., Toxicol Sci. 2013 Mar;132(1):21-31. doi: 10.1093/toxsci/kfs340. Epub 2013 Jan 3.
RGD ID: 10054107
Pubmed: PMID:23288050   (View Abstract at PubMed)
DOI: DOI:10.1093/toxsci/kfs340   (Journal Full-text)

Circulating liver-specific mRNAs such as albumin (Alb) and alpha-1-microglobulin/bikunin precursor (Ambp) have been reported to be potential biomarkers for drug-induced liver injury (DILI). We identified novel circulating liver-specific mRNAs and quantified them, together with the two previously reported mRNAs, in plasma from rats treated with various hepatotoxicants to validate circulating liver-specific mRNAs as biomarkers for DILI. Among six genes selected from the database, high liver specificity of apolipoprotein h (Apoh) and group-specific component (Gc) mRNAs were confirmed by reverse transcription (RT)-PCR and the copy numbers of these mRNAs elevated in plasma from rats treated with thioacetamide. Liver-specific mRNAs (Alb, Ambp, Apoh, and Gc) were quantified by real-time RT-PCR in plasma from rats with single dosing of seven hepatotoxicants. There were noticeable interindividual and intercompound variabilities in the severity of liver injury. The levels of four mRNAs increased almost in parallel and correlated with changes in the alanine aminotransferase (ALT) values and the hepatocellular necrosis scores at 24h after dosing. It was noteworthy that the magnitude of the increases in mRNA levels was greater than that in the ALT value. Time course analysis within 24h after dosing revealed that the timing of the increase was different among mRNA species, and the plasma levels of Alb and Gc mRNAs increased substantially earlier than the ALT values, suggesting that patterns of changes in circulating liver-specific mRNAs indicate the progression of liver injury. These results strongly support the reliability and usefulness of the four circulating liver-specific mRNAs as biomarkers for DILI.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Chemical and Drug Induced Liver Injury  ISOApoh (Rattus norvegicus)10054107; 10054107mRNA:increased expression:plasma:RGD 
Chemical and Drug Induced Liver Injury  IEP 10054107mRNA:increased expression:plasma:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Apoh  (apolipoprotein H)

Genes (Mus musculus)
Apoh  (apolipoprotein H)

Genes (Homo sapiens)
APOH  (apolipoprotein H)


Additional Information