Exploration of Biomarkers for Amoxicillin/Clavulanate‐Induced Liver Injury: Multi‐Omics Approaches

To explore potential biomarkers for amoxicillin/clavulanate‐induced liver injury (AC‐DILI), we conducted a clinical trial in 32 healthy subjects based on multi‐omics approaches. Every subject was administered amoxicillin/clavulanate for 14 days. The liver‐specific microRNA‐122 (miR‐122) level increa...

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Bibliographic Details
Published in:Clinical and translational science 2017-05, Vol.10 (3), p.163-171
Main Authors: Lee, J, Ji, SC, Kim, B, Yi, S, Shin, KH, Cho, JY, Lim, KS, Lee, SH, Yoon, SH, Chung, JY, Yu, KS, Park, HS, Kim, SH, Jang, IJ
Format: Article
Language:English
Subjects:
Adult
Alanine
Alanine transaminase
Alanine Transaminase - blood
Alcohol
Alternating current
Amoxicillin
Amoxicillin - adverse effects
Amoxicillin - pharmacokinetics
Analgesics
Antibiotics
Antigens
Bioindicators
Biomarkers
Biomarkers - blood
Biomarkers - metabolism
Biomarkers - urine
Cell Proliferation
Chemical and Drug Induced Liver Injury - blood
Chemical and Drug Induced Liver Injury - metabolism
Chemical and Drug Induced Liver Injury - urine
Chromatography
Clavulanic Acid - adverse effects
Clavulanic Acid - pharmacokinetics
Clinical trials
Demography
Enzymatic activity
Enzymes
Humans
Liver
Lymphocytes
Lymphocytes - metabolism
Male
Metabolites
Metabolome
MicroRNAs
MicroRNAs - blood
miRNA
Oxidative stress
Penicillin
Prescription drugs
Studies
Time Factors
Urine
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Summary:To explore potential biomarkers for amoxicillin/clavulanate‐induced liver injury (AC‐DILI), we conducted a clinical trial in 32 healthy subjects based on multi‐omics approaches. Every subject was administered amoxicillin/clavulanate for 14 days. The liver‐specific microRNA‐122 (miR‐122) level increased prior to and correlated well with the observed alanine aminotransferase (ALT) level increase. This result indicates its potential as a sensitive early marker for AC‐DILI. We also identified urinary metabolites, such as azelaic acid and 7‐methylxanthine, with levels that significantly differed among the groups classified by ALT elevation level on day 8 after drug administration (P < 0.05). Lymphocyte proliferation in response to the drug was also observed. These findings demonstrate sequential changes in the process of AC‐DILI, including metabolic changes, increased miR‐122 level, increased liver enzyme activity, and enhanced lymphocyte proliferation after drug administration. In conclusion, this study provides potential biomarkers for AC‐DILI based on currently known mechanisms using comprehensive multi‐omics approaches.
ISSN:1752-8054
1752-8062
DOI:10.1111/cts.12425