PMID- 24038040 OWN - NLM STAT- MEDLINE DCOM- 20150409 LR - 20161125 IS - 1099-1263 (Electronic) IS - 0260-437X (Linking) VI - 34 IP - 9 DP - 2014 Sep TI - Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury. PG - 993-1001 LID - 10.1002/jat.2917 [doi] AB - Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker identification, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PCLS were incubated with acetaminophen (APAP), 3-acetamidophenol, diclofenac and lipopolysaccharide for 24-48 h. PCLS medium from all species treated with APAP demonstrated similar changes in protein profiles, as previously found in mouse urine after APAP-induced liver injury, including the same key proteins: superoxide dismutase 1, carbonic anhydrase 3 and calmodulin. Further analysis showed that the concentration of hepcidin, a hepatic iron-regulating hormone peptide, was reduced in PCLS medium after APAP treatment, resembling the decreased mouse plasma concentrations of hepcidin observed after APAP treatment. Interestingly, comparable results were obtained after 3-acetamidophenol incubation in rat and human, but not mouse PCLS. Incubation with diclofenac, but not with lipopolysaccharide, resulted in the same toxicity parameters as observed for APAP, albeit to a lesser extent. In conclusion, proteomics can be applied to identify potential translational biomarkers using the PCLS system. CI - Copyright (c) 2013 John Wiley & Sons, Ltd. FAU - van Swelm, Rachel P L AU - van Swelm RP AD - Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, the Netherlands. FAU - Hadi, Mackenzie AU - Hadi M FAU - Laarakkers, Coby M M AU - Laarakkers CM FAU - Masereeuw, Rosalinde AU - Masereeuw R FAU - Groothuis, Geny M M AU - Groothuis GM FAU - Russel, Frans G M AU - Russel FG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130830 PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (Biomarkers) RN - 0 (Calmodulin) RN - 0 (Hepcidins) RN - 0 (Lipopolysaccharides) RN - 0 (SOD1 protein, human) RN - 144O8QL0L1 (Diclofenac) RN - 362O9ITL9D (Acetaminophen) RN - EC 1.15.1.1 (Sod1 protein, mouse) RN - EC 1.15.1.1 (Sod1 protein, rat) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 1.15.1.1 (Superoxide Dismutase-1) RN - EC 4.2.1.- (Carbonic Anhydrase III) SB - IM MH - Acetaminophen/administration & dosage/toxicity MH - Animals MH - Biomarkers/*urine MH - Calmodulin/metabolism MH - Carbonic Anhydrase III/metabolism MH - Chemical and Drug Induced Liver Injury/*diagnosis MH - Diclofenac/administration & dosage/toxicity MH - *Gene Expression Profiling MH - Hepcidins/metabolism MH - Humans MH - Lipopolysaccharides/administration & dosage/toxicity MH - Liver/*drug effects/metabolism MH - Mice MH - *Proteomics MH - Rats MH - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MH - Superoxide Dismutase/metabolism MH - Superoxide Dismutase-1 MH - Toxicity Tests OTO - NOTNLM OT - Precision-cut liver slices OT - acetaminophen OT - diclofenac OT - drug-induced liver injury OT - hepcidin OT - proteomics profiling EDAT- 2013/09/17 06:00 MHDA- 2015/04/10 06:00 CRDT- 2013/09/17 06:00 PHST- 2013/05/27 00:00 [received] PHST- 2013/06/21 00:00 [revised] PHST- 2013/07/09 00:00 [accepted] PHST- 2013/09/17 06:00 [entrez] PHST- 2013/09/17 06:00 [pubmed] PHST- 2015/04/10 06:00 [medline] AID - 10.1002/jat.2917 [doi] PST - ppublish SO - J Appl Toxicol. 2014 Sep;34(9):993-1001. doi: 10.1002/jat.2917. Epub 2013 Aug 30.