title: Exploration of Biomarkers for Amoxicillin/Clavulanate-Induced Liver Injury: Multi-Omics Approaches.
abstract: 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.
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: J
authors: J
authors: Lee
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: S C
authors: SC
authors: Ji
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: B
authors: B
authors: Kim
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: S
authors: S
authors: Yi
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
authors: K H
authors: KH
authors: Shin
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: J Y
authors: JY
authors: Cho
authors: Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Korea.
authors: K S
authors: KS
authors: Lim
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: S H
authors: SH
authors: Lee
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: S H
authors: SH
authors: Yoon
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea.
authors: J Y
authors: JY
authors: Chung
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: K S
authors: KS
authors: Yu
authors: Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors: H S
authors: HS
authors: Park
authors: Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors: S H
authors: SH
authors: Kim
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors: I J
authors: IJ
authors: Jang
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000658:Amoxicillin / Q000009:adverse effects* / Q000493:pharmacokinetics; D015415:Biomarkers / Q000097:blood / Q000378:metabolism* / Q000652:urine; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism* / Q000652:urine; D019818:Clavulanic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics; D003710:Demography; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D055442:Metabolome; D035683:MicroRNAs / Q000097:blood; D013997:Time Factors
chemical_list: D015415:Biomarkers; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D019818:Clavulanic Acid; D000658:Amoxicillin; D000410:Alanine Transaminase