High-content analysis/screening for predictive toxicology: Application to hepatotoxicity and genotoxicity

Basic and Clinical Pharmacology and Toxicology

Volumn 115, Issue 1, 2014, Pages 18-23

  Persson, Mikael ^a   Løye, Anni F ^a   Jacquet, Mélanie ^a   Mow, Natacha S ^a   Thougaard, Annemette V ^a   Mow, Tomas ^a   Hornberg, Jorrit J ^a  

^a H LUNDBECK A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; AMOXICILLIN; BILE SALT; BILE SALT EXPORT PUMP; BOSENTAN; CAFFEINE; CHOLESTEROL; CYCLOSPORIN; ERYTHROMYCIN ESTOLATE; FLUMAZENIL; FLUORESCENT DYE; FLUOXETINE; FUSIDIC ACID; IBUPROFEN; ISOPRENALINE; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 2; NEFAZODONE; PARGYLINE; PHOSPHATIDYLCHOLINE; PHOSPHOLIPID; PIOGLITAZONE; RIFAMPICIN; RITONAVIR; ROSIGLITAZONE; TROGLITAZONE; BILE ACID;

ADVERSE OUTCOME; ARTICLE; CELL LEVEL; CHOLESTASIS; COST; COVALENT BOND; CYTOTOXICITY; DRUG INDUSTRY; ENTEROHEPATIC CIRCULATION; GENOTOXICITY; HIGH CONTENT SCREENING; HUMAN; IMAGE ANALYSIS; IN VITRO STUDY; LIVER CELL; LIVER TOXICITY; MICRONUCLEUS; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL TOXICITY; MITOCHONDRION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PRIORITY JOURNAL; SCREENING; TOXIC HEPATITIS; ANIMAL; ANTAGONISTS AND INHIBITORS; COST BENEFIT ANALYSIS; DNA DAMAGE; DRUG EFFECTS; DRUG-INDUCED LIVER INJURY; LIVER; METABOLISM; PROCEDURES; TOXICITY TESTING;

ANIMALIA;

ANIMALS; BILE ACIDS AND SALTS; CHOLESTASIS; COST-BENEFIT ANALYSIS; DNA DAMAGE; DRUG-INDUCED LIVER INJURY; HEPATOCYTES; HUMANS; LIVER; TOXICITY TESTS;

EID: 84902074103     PISSN: 17427835     EISSN: 17427843     Source Type: Journal    
DOI: 10.1111/bcpt.12200     Document Type: Article

References (29)

1. Hornberg JJ, Laursen M, Brenden N, Persson M, Thougaard AV, Toft DB et al. Exploratory toxicology as an integrated part of drug discovery - Part I: why and how. Drug Discov Today 2013; [Epub ahead of print].
2. Hornberg JJ, Laursen M, Brenden N, Persson M, Thougaard AV, Toft DB et al. Exploratory toxicology as an integrated part of drug discovery - Part II: screening strategies. Drug Discov Today 2013; [Epub ahead of print].
3. O'Brien PJ, Irwin W, Diaz D, Howard-Cofield E, Krejsa CM, Slaughter MR 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;80:580-604.
4. Xu JJ, Henstock PV, Dunn MC, Smith AR, Chabot JR, de GD. Cellular imaging predictions of clinical drug-induced liver injury. Toxicol Sci 2008;105:97-105.
5. Persson M, Loye AF, Mow T, Hornberg JJ. A high content screening assay to predict human drug-induced liver injury during drug discovery. J Pharmacol Toxicol Methods 2013;68:302-13.
6. Tolosa L, Pinto S, Donato MT, Lahoz A, Castell JV, O'Connor JE et al. Development of a multiparametric cell-based protocol to screen and classify the hepatotoxicity potential of drugs. Toxicol Sci 2012;127:187-98.
7. Dykens JA, Will Y. The significance of mitochondrial toxicity testing in drug development. Drug Discov Today 2007;12:777-85.
8. Porceddu M, Buron N, Roussel C, Labbe G, Fromenty B, Borgne-Sanchez A. Prediction of liver injury induced by chemicals in human with a multiparametric assay on isolated mouse liver mitochondria. Toxicol Sci 2012;129:332-45.
9. Ong MM, Latchoumycandane C, Boelsterli UA. Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities. Toxicol Sci 2007;97:205-13.
10. Stepan AF, Walker DP, Bauman J, Price DA, Baillie TA, Kalgutkar AS et al. Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States. Chem Res Toxicol 2011;24:1345-410.
11. Nakayama S, Atsumi R, Takakusa H, Kobayashi Y, Kurihara A, Nagai Y et al. A zone classification system for risk assessment of idiosyncratic drug toxicity using daily dose and covalent binding. Drug Metab Dispos 2009;37:1970-7.
12. Nicolaou M, Andress EJ, Zolnerciks JK, Dixon PH, Williamson C, Linton KJ. Canalicular ABC transporters and liver disease. J Pathol 2012;226:300-15.
13. St-Pierre MV, Kullak-Ublick GA, Hagenbuch B, Meier PJ. Transport of bile acids in hepatic and non-hepatic tissues. J Exp Biol 2001;204:1673-86.
14. Kubitz R, Droge C, Stindt J, Weissenberger K, Haussinger D. The bile salt export pump (BSEP) in health and disease. Clin Res Hepatol Gastroenterol 2012;36:536-53.
15. Dawson S, Stahl S, Paul N, Barber J, Kenna JG. In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Drug Metab Dispos 2012;40:130-8.
16. Stieger B. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug Metab Rev 2010;42:437-45.
17. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, Lecluyse EL et al. Early identification of clinically relevant drug interactions with the human Bile Salt Export Pump (BSEP/ABCB11). Toxicol Sci 2013;136:328-43.
18. Lechner C, Reichel V, Moenning U, Reichel A, Fricker G. Development of a fluorescence-based assay for drug interactions with human Multidrug Resistance Related Protein (MRP2; ABCC2) in MDCKII-MRP2 membrane vesicles. Eur J Pharm Biopharm 2010;75:284-90.
19. Mills CO, Milkiewicz P, Saraswat V, Elias E. Cholyllysyl fluroscein and related lysyl fluorescein conjugated bile acid analogues. Yale J Biol Med 1997;70:447-57.
20. Jemnitz K, Veres Z, Vereczkey L. Contribution of high basolateral bile salt efflux to the lack of hepatotoxicity in rat in response to drugs inducing cholestasis in human. Toxicol Sci 2010;115:80-8.
21. Lee J, Azzaroli F, Wang L, Soroka CJ, Gigliozzi A, Setchell KD et al. Adaptive regulation of bile salt transporters in kidney and liver in obstructive cholestasis in the rat. Gastroenterology 2001;121:1473-84.
22. Thompson RA, Isin EM, Li Y, Weidolf L, Page K, Wilson I et al. In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs. Chem Res Toxicol 2012;25:1616-32.
23. Tilmant K, Gerets HH, De RP, Cossu-Leguille C, Vasseur P, Dhalluin S et al. The automated micronucleus assay for early assessment of genotoxicity in drug discovery. Mutat Res 2013;751:1-11.
24. Kirsch-Volders M, Plas G, Elhajouji A, Lukamowicz M, Gonzalez L, Vande LK et al. The in vitro MN assay in 2011: origin and fate, biological significance, protocols, high throughput methodologies and toxicological relevance. Arch Toxicol 2011;85:873-99.
25. Fenech M. The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations. Environ Health Perspect 1993;101(Suppl 3):101-7.
26. Bryce SM, Bemis JC, Avlasevich SL, Dertinger SD. In vitro micronucleus assay scored by flow cytometry provides a comprehensive evaluation of cytogenetic damage and cytotoxicity. Mutat Res 2007;630:78-91.
27. Schuler M, Rupa DS, Eastmond DA. A critical evaluation of centromeric labeling to distinguish micronuclei induced by chromosomal loss and breakage in vitro. Mutat Res 1997;392:81-95.
28. Earnshaw W, Bordwell B, Marino C, Rothfield N. Three human chromosomal autoantigens are recognized by sera from patients with anti-centromere antibodies. J Clin Invest 1986;77:426-30.
29. ICH Guideline S2 (R1). Guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use S2(R1). EMEA 2011;www.ema.europa.eu/ema.