Test systems in drug discovery for hazard identification and risk assessment of human drug-induced liver injury

References

• Kaplowitz N, DeLeve L. Drug-Induced liver disease. 3rd ed. los Angeles: Academic Press; 2013.
   Google Scholar
• Olson H, Betton G, Robinson D, et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol. 2000;32(1):56–67.
   PubMed Web of Science ®Google Scholar
• Godoy P, Hewitt N, Albrecht U, et al. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol. 2013;87(8):1315–1530.
   PubMed Web of Science ®Google Scholar
• Gómez-Lechón M, Tolosa L, Conde I, et al. Competency of different cell models to predict human hepatotoxic drugs. Expert Opinion Drug Metab Toxicol. 2014;10(11):1553–1568.
   PubMed Web of Science ®Google Scholar
• Lin C, Ballinger K, Khetani S. The application of engineered liver tissues for novel drug discovery. Expert Opin Drug Discov. 2015;10(5):519–540.
   PubMed Web of Science ®Google Scholar
• Dragovic S, Vermeulen N, Gerets H, et al. Evidence-based selection of training compounds for use in the mechanism-based integrated prediction of drug-induced liver injury in man. Arch Toxicol. 2016;90:1–25.
   Web of Science ®Google Scholar
• Roth R, Ganey P. Animal models of idiosyncratic drug-induced liver injury—current status. Crit Rev Toxicol. 2011;41(9):723–739.
   PubMed Web of Science ®Google Scholar
• Peters T. Do preclinical testing strategies help predict human hepatotoxic potentials? Toxicol Pathol. 2005;33(1):146–154.
   PubMed Web of Science ®Google Scholar
• Benbow J, Aubrecht J, Banker M, et al. Predicting safety toleration of pharmaceutical chemical leads: cytotoxicity correlations to exploratory toxicity studies.. Toxicol Lett. 2010;197:175–182.
   PubMed Web of Science ®Google Scholar
• Abraham V, Towne D, Waring JF, et al. Application of a high-content multiparameter cytotoxicity assay to prioritize compounds based on toxicity potential in humans. J Biomed Screen. 2008;13(6):527–537.
   PubMedGoogle Scholar
• Persson M, Loye A, Mow T, et al. A high content screening assay to predict human drug-induced liver injury during drug discovery. J Pharmacol Toxicol Methods. 2013;68(3):302–313.
   PubMed Web of Science ®Google Scholar
• Riss T, Moravec R, Niles A, et al. Cell Viability Assays. In: Sittampalam G, Coussens N, Nelson H, et al. Eds.. Assay Guidance Manual. MD, Bethesda:2016.
   Google Scholar
• Persson M, Hornberg J. Advances in predictive toxicology for discovery safety through high content screening. Chem Res Toxicol. 2016 Oct 21;29:1998–2007.
   PubMed Web of Science ®Google Scholar
• Bopp S, Lettieri T. Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrfish liver cell line. BMC Pharmacol. 2008;8(1):8.
   PubMedGoogle Scholar
• Borenfreund E, Puerner J. Toxicity determined in vitro by morphological alterations and Neutral Red absorption. Toxicology Lett. 1985;24:119–124.
   PubMed Web of Science ®Google Scholar
• Atienzar F, Gerets H, Tilmant K, et al. Evaluation of Impedance-Based Label-Free Technology as a Tool for Pharmacology and Toxicology Investigations. Biosensors. 2013;3(1):132–156.
   PubMedGoogle Scholar
• Park S, Choi Y, Lee B. In vitro validation of drug-induced phospholipidosis. J Toxicol Sci. 2012;37(2):261–267.
   PubMed Web of Science ®Google Scholar
• Goldring C, Weaver R, Kramer B, et al. Drug-Induced Liver Injury: mechanism-Informed Prediction in Drug. In : Comprehensive Medicinal Chemistry. 3rd. Oxford, Elsevier; The Netherlands; 2017. 1–18.
   Google Scholar
• Persson M, Løye, . AF, Mow T, et al. A high content screening assay to predict human drug-induced liver injury during drug discovery. J Pharmacol Toxicol Methods. 2014;68(3):302–313.
   Web of Science ®Google Scholar
• Lin L, Will Y. Evalaution of drugs with specific organ toxicities in organ-specific cell lines. Toxicologial Sci. 2012;126:114–127.
   PubMed Web of Science ®Google Scholar
• Marx U, Andersson T, Bahinski A, et al. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. Altex. 2016;33(3):272–321.
   PubMedGoogle Scholar
• Sison-Young R, Mitsa D, Jenkins RE, et al. Comparative proteomic characterization of 4 human liver-derived single cell culture models reveals significant variation in the capacity for drug disposition, bioactivation, and detoxication. Toxicol Sci. 2015 Oct;147(2):412–424.
   PubMed Web of Science ®Google Scholar
• Gerets HH, Hanon E, Cornet M, et al. Selection of cytotoxicity markers for the screening of new chemical entities in a pharmaceutical context: a preliminary study using a multiplexing approach. Toxico. Toxicol Vitro. 2009;23:319–332.
   PubMed Web of Science ®Google Scholar
• Schoonen W, De Roos J, Westerink W, et al. Cytotoxic effects of 110 reference compounds on HepG2 cells and for 60 compounds on HeLa, ECC-1 and CHO cells. II Mechanistic assays on NAD(P)H, ATP and DNA contents. Toxicology In Vitro. 2005a;19:491–503.
   PubMed Web of Science ®Google Scholar
• Schoonen W, Westerink W, De Roos J, et al. Cytotoxic effects of 100 reference compounds on HepG2 and HeLa cells and of 60 compounds on ECC-1 and CHO cells. I. Mechanistic assays on ROS,glutathione depletion and calcein uptake. Toxicol Vitro. 2005b;19:505–516.
   PubMed Web of Science ®Google Scholar
• O’Brien P, Irwin W, Diaz D, et al. High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening. Arch Toxicol. 2006;80(9):580–604.
   PubMed Web of Science ®Google Scholar
• Hewitt N, Hewitt P. Phase I and II enzyme characterization of two sources of HepG2 cell lines. Xenobiotica. 2004;34:243–256.
   PubMed Web of Science ®Google Scholar
• McBride H, Neuspiel M, Wasiak S. Mitochondria more than just a powerhouse. Curr Biol. 2006;16(14):551–560.
   PubMed Web of Science ®Google Scholar
• Dykens J, Will Y. The significance of mitochondrial toxicity testing in drug development. Drug Discovery Today. 2007;12:777–785.
   PubMed Web of Science ®Google Scholar
• Pessayre D, Fromenty B, Berson A, et al. Central role of mitochondria in drug-induced liver injury. Drug Metab Rev. 2012;44:34–87.
   PubMed Web of Science ®Google Scholar
• Fromenty B. Drug-induced liver injury in obesity. J Hepatol. 2013;58:824–826.
   PubMed Web of Science ®Google Scholar
• Nadanaciva S, Willis J, Barker M, et al. Assessment of drug-induced mitochondrial dysfunction via altered cellular respiration and acidification measured in a 96-well platform. J Bioenerg Biomembr. 2012;44(4):421–437.
   PubMed Web of Science ®Google Scholar
• Begriche K, Massart J, Robin M, et al. Drug-induced toxicity on mitochondria and lipid metabolism: mechanistic diversity and deleterious consequences for the liver. J Hepatol. 2011;54(4):773–794.
   PubMed Web of Science ®Google Scholar
• McKee E, Ferguson M, Bentley A, et al. Inhibition of mammalian mitocondrial protein synthesis by oxazolidinones. Antimicrobial Agents Chemother. 2006;50(6):2042–2049.
   PubMed Web of Science ®Google Scholar
• De Bus L, Depuydt P, Libbrecht L, et al. Servere drug-induced liver injury associated with prolonged use of linezolid. J Med Toxicol. 2010;6:322–326.
   PubMedGoogle Scholar
• Marroquin L, Hynes J, Dykens J, et al. Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicol Sci. 2007;97(2):539–547.
   PubMed Web of Science ®Google Scholar
• Swiss R, Will Y. Assessment of mitochondrial toxicity in HepG2 cells cultured in high-glucose- or galactose-containing media. Curr. Protoc. Toxicol. 2011;49:2.20:2.20.1–2.20.14.
   Google Scholar
• Kamalian L, Chadwick A, Bayliss M, et al. The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death. Toxicol Vitro. 2015;29:732–740.
   PubMed Web of Science ®Google Scholar
• Marchandeau J, Labbe G. Evaluation of mitochondrial respiration in cultured rat hepatocytes. Methods Mol Biol. 2011;691:243–253.
   PubMedGoogle Scholar
• Pereira S, Pereira G, Moreno A, et al. Can drug safety be predicted and animal experiments reduced by using isolated mitochondrial fractions? Altern Lab Anim. 2009;37:355–365.
   PubMed Web of Science ®Google Scholar
• Eakins J, Bauch C, Woodhouse H, et al. A combined in vitro approach to improve the prediction of mitochondrial toxicants. Toxicol In Vitro. 2016 Apr;12:161–170.
   Web of Science ®Google Scholar
• Massart J, Robin M, Noury F, et al. Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis. Br J Pharmacol. 2012;165:1361–1374.
   PubMed Web of Science ®Google Scholar
• Aubert J, Begriche K, Delannoy M, et al. Differences in early acetaminophen hepatotoxicity between obese ob/ob and db/db mice.,”. J Pharmacol Exp Ther. 2012;342:676–687.
   PubMed Web of Science ®Google Scholar
• Weglewska-Jurkiewicz A, Jakóbkiewicz-Banecka J, Pronicka E, et al. False positive results of mitochondrial DNA depletion/deletion due to single nucleotide substitutions causing appearance of additional PvuII restriction sites. Diagn Mol Pathol. 2007;16(2):116–120.
   PubMedGoogle Scholar
• Lianga C, Ahmada K, Suea C. The broadening spectrum of mitochondrial disease: shifts in the diagnostic paradigm. Biochimica Et Biophysica Acta (BBA) - General Subjects. 2013;1840(4):1360–1367.
   PubMed Web of Science ®Google Scholar
• Haas R, Parikh S, Falk M, et al. The in-depth evaluation of suspected mitochondrial disease. Mol Genet Metab. 2008;94(1):16–37.
   PubMed Web of Science ®Google Scholar
• Aleo MD, Luo Y, Swiss R, et al. Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump. Hepatology. 2014;60(3):1015–1022.
   PubMed Web of Science ®Google Scholar
• Dykens J, Marroquin L, Will Y. Strategies to reduce late-stage drug attrition due to mitochondrial toxicity. Expert Rev Mol Diagn. 2007 Mar;7(2):161–175.
   PubMed Web of Science ®Google Scholar
• Xu J, Henstock P, Dunn M, et al. Cellular imaging predictions of clinical drug-induced liver injury. Toxicol Sci. 2008;105(1):97–105.
   PubMed Web of Science ®Google Scholar
• Hynes J, Marroquin LD, Christiansen K, et al. Investigation of drug-induced mitochondrial toxicity using fluorescence-based oxygen-sensitive probes. Toxicological Sci. 2006;92:186–200.
   PubMed Web of Science ®Google Scholar
• Ball A, Kamalian L, Alfirevic A, et al. Identification of the additional mitochondrial liabilities of 2-hydroxyflutamide when compared with its parent compound, Flutamide in HepG2 Cells. Toxicol Sci. 2016;153(2):341–351.
   PubMed Web of Science ®Google Scholar
• Nadanaciva S, Bernal A, Aggeler R, et al. Target identification of drug induced mitochondrial toxicity using immunocapture based OXPHOS activity assays. Toxicoloy in Vitro. 2007;21(5):902–911.
   PubMed Web of Science ®Google Scholar
• Ojuka E, Andrew B, Bezuidenhout N, et al. “Measurement of β-oxidation capacity of biological samples by respirometry: a review of principles and substrates,”. . American Journal of Physiology - Endocrinology and Metabolism. 2016;310:715–723.
   Web of Science ®Google Scholar
• Perry S, Norman J, Barbieri J, et al. Mitochondrial membrane potential probes and the proton gradient: a practical usage guide. Biotechniques. 2011 Feb;50(2):98–115.
   PubMed Web of Science ®Google Scholar
• Broom A, Ambroso J, Brunori G, et al. Effects of mid-respiratory chain inhibition on mitochondrial function in vitro and in vivo. Toxicol Res. 2016;5:136–150.
   Web of Science ®Google Scholar
• Will Y, Dykens J. Mitochondrial toxicity assessment in industry – a decade of technology development and insight. Expert Opin Drug Metab Toxicol. 2014;10(8):1061–1067.
   PubMed Web of Science ®Google Scholar
• Ong M, Wang A, Leow K, et al. Nimesulide-induced hepatic mitochondrial injury in heterologous SOD2(+/-) mice. Free Radical Biol Med. 2006;40:420–429.
   PubMed Web of Science ®Google Scholar
• Ong MMK, Latchoumycandane C, Boelsterli U. Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities. Toxicol Sci. 2007;97:205–213.
   PubMed Web of Science ®Google Scholar
• Xu D, Nishimura T, Nishimura S, et al. Fialuridine induces acute liver failure in chimeric TK-NOG Mice: a model for detecting hepatic drug toxicity prior to human testing. PLoS Medicine. 2014;11(4):1001628.
   PubMed Web of Science ®Google Scholar
• Kashimshetty R, Desai V, Kale V, et al. Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity. Toxicol Appl Pharmacol. 2009;238(2):150–159.
   PubMed Web of Science ®Google Scholar
• Fujimoto K, Kumagai K, Ito K, et al. Sensitivity of liver injury in heterozygous sod2 knockout mice treated with troglitazone or acetaminophen. Toxicol Pathol. 2009;37:193–200.
   PubMed Web of Science ®Google Scholar
• Festing M. Improving toxicity screening and drug development by using genetically defined strains. Methods Mol Biol. 2010;602:1–21.
   PubMedGoogle Scholar
• Montaner J, Coté H, Harris R, et al. Nucleoside-related mitochondrial toxicity among HIV-infected patients receiving antiretroviral therapy; Insights from the evaluation of venous lactic acid and periperal blood mitochondrial DNA. Clin Infect; Dis. 2004;38(2):S73–79.
   PubMed Web of Science ®Google Scholar
• Hailey J, Nold J, Brown R, et al. Biliary proliferative lesions in the Sprague-Dawley rat: adverse/non-adverse. Toxicol Pathol. 2014;42(5):844–854.
   PubMed Web of Science ®Google Scholar
• Burbank M, Burben A, Sharanek A, et al. Early alterations of bile canaliculi dynamics and the Rho kinase/myosyn light chain kinase pathway are characteristics of drug-induced intrahepatic cholestasis. Drug Met Disposition. 2016;44:1–14.
   PubMed Web of Science ®Google Scholar
• Persson M, Løye A, Jacquet M, et al. High-content analysis/screening for predictive toxicology: application to hepatotoxicity and genotoxicity. Basic Clin Pharmacol Toxicol. 2014;115(1):18–23.
   PubMed Web of Science ®Google Scholar
• Köck K, Ferslew B, Netterberg I, et al. Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters multidrug resistance-associated proteins 3 and 4. Drug Met Dispos. 2014;42:665–674.
   PubMed Web of Science ®Google Scholar
• Morgan RE, Van Staden C, Chen Y, et al. A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Tox Sciences. 2013 August;16; 136.
   Web of Science ®Google Scholar
• Blomme E, Will Y. Toxicology strategies for drug discovery: present and future. Chem Res Toxicol. 2016;29(4):473–504.
   PubMed Web of Science ®Google Scholar
• Li T, Chiang YT. Bile acid signalling in metabolic disease and drug therapy. Pharm Rev. 2014;66:948–983.
   PubMed Web of Science ®Google Scholar
• Rogue A, Anthérieu S, Vluggens T, et al. PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells. Tox and Appl Pharm. 2014;276:73–81.
   PubMed Web of Science ®Google Scholar
• Starokozhk V, Vatakuti S, Schievink B, et al. Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days. Arch Toxicol. 2016 October;7;91.
   Web of Science ®Google Scholar
• Vatakuti S, Pennings J, Gore E, et al. Classification of cholestatic and necrotic hepatotoxicants using transcriptomics on human precision-cut liver slices. Chem Res Toxicol. 2016 March 9:342–351.
   PubMed Web of Science ®Google Scholar
• Le Vee M, Noel G, Joudan E, et al. Polarized experssion of drug transporters in differentiated human hepatoma HepaRG cells. Toxicol Vitro. 2013;6:1976–1986.
   Google Scholar
• Racanelli V, Rehermann B. The liver as an immunological organ. Hepatology. 2006;43(2 suppl 1):S54–62.
   PubMed Web of Science ®Google Scholar
• Robinson M, Harmon C, O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Olecular Immunol. 2016;13:267–276.
   PubMed Web of Science ®Google Scholar
• Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discovery. 2005;4:489–499.
   PubMed Web of Science ®Google Scholar
• Laverty H, Antoine D, Benson C, et al. The potential of cytokines as safety biomarkers for drug-induced liver injury. Eur J Clin Pharmacol. 2010;66:961–975.
   PubMed Web of Science ®Google Scholar
• Mennicke M, Zawodniak A, Keller M, et al. Fulminant liver failure after vancomycin in a sulfasalazine-induced DRESS syndrome: fatal recurrence after liver transplatation. Am J Translpantation. 2009;9:2197–2202.
   PubMed Web of Science ®Google Scholar
• James L, Simpson P, Farrar H, et al. Cytokines and toxicity in acetaminophen overdose. J Clin Pharmacol. 2005;45:1165–1171.
   PubMed Web of Science ®Google Scholar
• Li J, Zhu X, Liu F, et al. Cytokine and autoantibody patterns in acute liver failure. J Immunotoxicol. 2010;7:157–164.
   PubMed Web of Science ®Google Scholar
• Kakisaka K, Takikawa Y. Elevation of serum cytokines preceding elevation of liver enzymes in a case of drug-induced liver injury.,”. J Gastroenterol Hepatol Res. 2014;44:E284–289.
   Google Scholar
• Berry P, Antoniades C, Hussain M, et al. Admission levels and early changes in serum interleukin-10 are predictive of poor outcome in acute liver failure and decompensated cirrhosis. Liver Int. 2010;30:733–740.
   PubMed Web of Science ®Google Scholar
• Monshi M, Faulkner L, Gibson A, et al. Human leukocyte antigen (HLA)-B*57:01-restricted activation. Hepatology. 2013;57(2):727–739.
   PubMed Web of Science ®Google Scholar
• Dubois-Pot-Schneider H, Fekir K, Coulouarn C, et al. Inflammatory cytokines promote the retrodifferentiation of tumor-derived hepatocyte-like cells to progenitor cells. Hepatology. 2014;60(6):2077–2090.
   PubMed Web of Science ®Google Scholar
• Usui T, Mise M, Hashizume T, et al. Evaluation of the potential for drug-induced liver injury based on in vitro covalent binding to human liver proteins. Drug Metab Dispos. 2009;37(12):2383–2392.
   PubMed Web of Science ®Google Scholar
• Oda S, Matsuo K, Nakajima A, et al. A novel cell-based assay for the evaluation of immune- and inflammatory-related gene expression as biomarkers for the risk assessment of drug-induced liver injury. Toxicol Lett. 2016;241:60–70.
   PubMed Web of Science ®Google Scholar
• Yano A, Oda S, Fukami TNM, et al. Development of a cell-based assay system considering drug metabolism and immune- and inflammatory-related factors for the risk assessment of drug-induced liver injury. Toxicol Lett. 2014;1:228.
   Google Scholar
• Stephens C, Andrade R, Lucena M. Mechanisms of drug-induced liver injury.,”. Curr Opin Allergy Clin Immunol. 2014;14(4):286–292.
   PubMed Web of Science ®Google Scholar
• Ju C, Reilly T. Role of immune reactions in drug-induced liver injury (DILI). Drug Metab Rev. 2012;44(1):107–115.
   PubMed Web of Science ®Google Scholar
• Papay J, Clines D, Rafi R, et al. Drug-induced liver injury following positive drug rechallenge. Regul Toxicol Pharmacol. 2009;54:84–90.
   PubMed Web of Science ®Google Scholar
• Ogese M, Ahmed S, Alferivic A, et al. New approaches to investigate drug-induced hypersensitivity. Chem Res Toxicol. 2017 November 2;30(1):239–259.
   PubMed Web of Science ®Google Scholar
• Metushi I, Sanders C, Lee W, et al. Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure. Hepatology. 2014;59:1084–1093.
   PubMed Web of Science ®Google Scholar
• Kim S, Saide K, Farrell J, et al. Characterization of amoxicillin- and clavulanic acid-specific T cells in patients with amoxicillin-clavulanate-induc. Hepatology. 2015;62(3):887–899.
   PubMed Web of Science ®Google Scholar
• Daly A, Donaldson P, Bhatnagar P, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genetics. 2009;41(7):816–819.
   PubMed Web of Science ®Google Scholar
• Spraggs CF, Budde L, Briley L, et al. HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breat cancer. J Clin Oncol. 2011;29(6):667–673.
   PubMed Web of Science ®Google Scholar
• Keisu M, Andersson T. Drug-induced liver injury in humans: the case of ximelagatran.,”. Handb Exp Pharmacol 407-18. 2010;196:407–418.
   Google Scholar
• Metushi I, Hayes M, Uetrecht J. Treatment of PD-1(-/-) mice with amodiaquine and anti-CTLA4 leads to liver injury similar to idiosyncratic liver injury in patients. Hepatology. 2015;61:1332–1342.
   PubMed Web of Science ®Google Scholar
• Nattrass R, Faulkner L, Vocanson M, et al. Activation of flucloxacillin-specific CD8+ T-cells with the potential to promote hepatocyte cytotoxicity in a mouse model. Toxicology. 2015;146:146–156.
   Web of Science ®Google Scholar
• Shaw P, Hopfensperger M, Ganey P, et al. Lipopolysaccharide and trovafloxacin coexposure in mice causes idiosyncrasy-like liver injury dependent on tumor necrosis factor-alpha. Toxicol Sci. 2007;100(1):259–266.
   PubMed Web of Science ®Google Scholar
• Waring J, Liguori M, Luyendyk J, et al. Microarray analysis of liopolysaccaride potentiation of trovafloxacin-induced liver proinflammatory chemokines and neutrophils. J Pharmacol Exp Ther. 2006;316(3):1080–1087.
   PubMed Web of Science ®Google Scholar
• Metushi I, Uetrecht J. Isoniazid-induced liver injury and immune response in mice. J Immunotoxicol. 2014;11(4):383–392.
   PubMed Web of Science ®Google Scholar
• Chakraborty M, Fullerton AM, Semple K, et al. Drug-induced allergic hepatitis develops in mice when myeloid-derived suppressor cells are depleted prior to halothane treatment. Hepatology. 2015;62(2):546–557.
   PubMed Web of Science ®Google Scholar
• Takai S, Higuchi S, Yano A, et al. Involvement of immune- and inflammatory-related factors in flucloxacillin-induced liver injury in mice. J Appl Toxicol. 2015;35:142–151.
   PubMed Web of Science ®Google Scholar
• Robles-Diaz M, Medina-Caliz I, Stephens C, et al. Biomarkers in DILI one more step forward. Front Pharmacol. 2016;7:267.
   PubMed Web of Science ®Google Scholar
• Hornby R, Starkey Lewis P, Dear J, et al. MicroRNAs as potential circulating biomarkers of drug-induced liver injury: key current and future issues for translation to humans. Expert Rev Clin Pharmacol. 2014;7:349–362.
   PubMed Web of Science ®Google Scholar
• Zhang M, Chen M, Tong W. Is toxicogenomics a more reliable and sensitive biomarker than conventional indicators from rats to predict drug-induced liver injury in humans? Chem Res Toxicol. 2012;25:122–129.
   PubMed Web of Science ®Google Scholar
• A. Smith, J. Calley, S. Mathur, et al. The Rat microRNA body atlas; evaluation of the microRNA content of rat organs through deep sequencing and characterization of pancreas enriched miRNAs as biomarkers of pancreatic toxicity in the rat and dog., BMC Genomics. 2016 Aug 30;17:694.
   PubMed Web of Science ®Google Scholar
• Fisher C, Bernard H, Wolenski F, et al. The beagle dog MicroRNA tissue atlas: identifying translatable biomarkers of organ toxicity.. BMC Gemomics. 2016 Nov;6;17.
   Google Scholar
• Califano A, Butte A, Friend S, et al. Leveraging models of cell regulation and GWAS data in integrative network-based association studies. Nat Genet. 2012;44:841–847.
   PubMed Web of Science ®Google Scholar
• Sutherland J, Jolly R, Goldstein K, et al. Assessing concordance of drug-induced transcriptional response in rodent liver and cultured hepatocytes. PLoS Comput Biol. 2016;12:e1004847.
   PubMed Web of Science ®Google Scholar
• Jiang J, Wolters J, Van Breda S, et al. Development of novel tools for the in vitro investigation of drug-induced liver injury. Expert Opin Drug Metab Toxicol. 2015;11:1523–1523.
   PubMed Web of Science ®Google Scholar
• Park B, Boobis A, Clarke S, et al. Managing the challenge of chemically reactive metabolites in drug development. Nat Rev Drug Discovery. 2011;10(4):292–306.
   PubMed Web of Science ®Google Scholar
• Thompson R, Isin E, Li M,Y, et al. in vitro appraoched to assess the potential for risk of idiosynratic adverse reactions caused by candidate drugs. Chem Res Toxicol. 2012;25(8):1616–1632.
   PubMed Web of Science ®Google Scholar
• Nakayama S, Atsumi R, Takakusa H, et al. A zone classification system for risk assessment of idiosyncratic drug toxicity using daily dose and covalent binding. Drug Met Dispos. 2009;37:1970–1977.
   PubMed Web of Science ®Google Scholar
• Obach R, Kalgutkar A, Soglia J, et al. Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from non-hepatotoxic drugs? An analysis of 18 drugs with consideration of intrinsic clearnace and daily dose. Chem Res Toxicol. 2008;21:1814–1822.
   PubMed Web of Science ®Google Scholar
• Sakatis M, Reese M, Harrell A, et al. preclinical stratergy to reduce clinical hepatotoxicity using in vitro bioactivation data for 200 compounds. Chem Res Toxicol. 2012;25(10):2067–2082.
   PubMed Web of Science ®Google Scholar
• Uetrecht J. New concepts in immunology relevant to idiosyncratic drug reactions: the “danger hypothesis” and innate immune system.,”. Chem Res Toxicol. 1999;12:387–395.
   PubMed Web of Science ®Google Scholar
• Walgren J, Mitchell M, Thompson D. Role of metabolism in drug-induced idiosyncratic hepatotoxicit. Crit Review Toxicol. 2005;35(4):325–361.
   PubMed Web of Science ®Google Scholar
• Sison-Young R, Lauschke V, Johann E, et al. A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity. Arch Toxicol. 2017;91(3):1385–1400.
   PubMed Web of Science ®Google Scholar
• Herzog N, Hansen M, Miethbauer S, et al. Primary-like human hepatocytes genetically engineered to obtain proliferation competence display hepatic differentiation characteristics in monolayer and organotypical spheroid cultures. Cell Biol Int. 2016;40(3):341–353.
   PubMed Web of Science ®Google Scholar
• Goldring C, Antoine D, Bonner F, et al. Stem cell-derived models to improve mechanistic understanding and prediction of human drug induced liver injury. Hepatology. 2016;65(2):710–721.
   PubMed Web of Science ®Google Scholar
• Hendriks D, Hendriks FPL, Messner S, et al. Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability. Sci Rep. 2016;6:Article number: 35434.
   Web of Science ®Google Scholar
• Goldring C, Norris A, Kitteringham N, et al. Mechanism-based markers of drug-induced liver injury to improve the physiological relevance and predictivity of in vitro models. Applied in Vitro Toxicology. 2015;1(3):175–186.
   Google Scholar
• Chen M, Bisgin H, Tong L, et al. Toward predictive models for drug-induced liver injury in humans: are we there yet? Biomarkers Med. 2014;8:201–213.
   PubMed Web of Science ®Google Scholar
• Naisbitt D, Yang E, Alhaidari M, et al. Towards depersonalized abacavir therapy: chemical modification eliminates HLA-B*57: 01-restricted CD8+ T-cell activation. Aids. 2015;29(18):2385–2395.
   PubMed Web of Science ®Google Scholar
• Goh J-Y, Weaver R, Dixon L, et al. Development and use of in vitro alternatives to animal testing by the pharmaceutical industry. Toxicol Res (Camb). 2015;4:1297–1307.
   Web of Science ®Google Scholar