Prediction of drug-induced hepatotoxicity using long-term stable primary hepatic 3D spheroid cultures in chemically defined conditions

Toxicological Sciences

Volumn 163, Issue 2, 2018, Pages 655-665

  Vorrink, Sabine U ^a   Zhou, Yitian ^a   Ingelman Sundberg, Magnus ^a   Lauschke, Volker M ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Drug development; In vitro; Liver; Species comparison; Toxicity screen

Indexed keywords

AFLATOXIN B1; ALBENDAZOLE; ALPIDEM; AMBRISENTAN; AMIODARONE; AMODIAQUINE; AZATHIOPRINE; BENOXAPROFEN; BOSENTAN; CLOMIPRAMINE; DACARBAZINE; DICLOFENAC; DIHYDRALAZINE; DISULFIRAM; FIALURIDINE; FLUCONAZOLE; FLUTAMIDE; GLAFENINE; GRISEOFULVIN; INDOMETACIN; IPRONIAZID; KETOCONAZOLE; LABETALOL; MEFENAMIC ACID; MERCAPTOPURINE; NEFAZODONE; PARACETAMOL; TOLCAPONE; TROGLITAZONE; UNINDEXED DRUG; NEW DRUG;

ANIMAL CELL; ARTICLE; CELL CULTURE; CONTROLLED STUDY; DISEASE CLASSIFICATION; DRUG CYTOTOXICITY; FALSE POSITIVE RESULT; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER CELL; LIVER FUNCTION; LIVER TOXICITY; MOUSE; NONHUMAN; PHENOTYPE; RAT; SENSITIVITY AND SPECIFICITY; TOXIC HEPATITIS; BIOLOGICAL MODEL; CELL SURVIVAL; DRUG EFFECT; MULTICELLULAR SPHEROID; PATHOLOGY; PRECLINICAL STUDY; PREDICTIVE VALUE; PRIMARY CELL CULTURE; PROCEDURES; TIME FACTOR;

CELL SURVIVAL; CELLS, CULTURED; CHEMICAL AND DRUG INDUCED LIVER INJURY; DRUG EVALUATION, PRECLINICAL; DRUGS, INVESTIGATIONAL; HEPATOCYTES; HUMANS; MODELS, BIOLOGICAL; PREDICTIVE VALUE OF TESTS; PRIMARY CELL CULTURE; SENSITIVITY AND SPECIFICITY; SPHEROIDS, CELLULAR; TIME FACTORS;

EID: 85048117176     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfy058     Document Type: Article

References (52)

1. Aithal, G. P. (2011). Hepatotoxicity related to antirheumatic drugs. Nat. Rev. Clin. Oncol. 7, 139-150
2. Bell, C. C., Dankers, A. C. A., Lauschke, V. M., Sison-Young, R., Jenkins, R., Rowe, C., Goldring, C., Park, K., Regan, S., Walker, T., et al. (2018). Comparison of hepatic 2D sandwich cultures and 3D spheroids for long-term toxicity applications: a multi-center study. Toxicol. Sci. 162, 655-666
3. Bell, C. C., Hendriks, D. F. G., Moro, S. M. L., Ellis, E., Walsh, J., Renblom, A., Fredriksson Puigvert, L., Dankers, A. C. A., Jacobs, F., Snoeys, J., et al. (2016). Characterization of primary human hepatocyte spheroids as amodel systemfor drug-induced liver injury, liver function and disease. Sci. Rep. 6, 25187
4. Bell, C. C., Lauschke, V. M., Vorrink, S. U., Palmgren, H., Duffin, R., Andersson, T. B., and Ingelman-Sundberg, M. (2017). Transcriptional, functional, and mechanistic comparisons of stem cell-derived hepatocytes, HepaRG cells, and threedimensional human hepatocyte spheroids as predictive in vitro systems for drug-induced liver injury. Drug Metab. Dispos. 45, 419-429
5. Bjö rnsson, E., Talwalkar, J., Treeprasertsuk, S., Kamath, P. S., Takahashi, N., Sanderson, S., Neuhauser, M., and Lindor, K. (2010). Drug-induced autoimmune hepatitis: Clinical characteristics and prognosis. Hepatology 51, 2040-2048
6. Chang, A., Krygier, D. S., Chatur, N., and Yoshida, E. M. (2009). Clozapine-induced fatal fulminant hepatic failure: A case report. Can. J. Gastroenterol. 23, 376-378
7. Chen, M., Vijay, V., Shi, Q., Liu, Z., Fang, H., and Tong, W. (2011). FDA-approved drug labeling for the study of drug-induced liver injury. Drug Discov. Today 16, 697-703
8. Choi, S. (2003). Nefazodone (Serzone) withdrawn because of hepatotoxicity. Can. Med. Assoc. J. 169, 1187-1187
9. Cook, D., Brown, D., Alexander, R., March, R., Morgan, P., Satterthwaite, G., and Pangalos, M. N. (2014). Lessons learned from the fate of AstraZeneca's drug pipeline: A fivedimensional framework. Nat. Rev. Drug Discov. 13, 419-431
10. Downing, N. S., Shah, N. D., Aminawung, J. A., Pease, A. M., Zeitoun, J.-D., Krumholz, H. M., and Ross, J. S. (2017). Postmarket safety events among novel therapeutics approved by the US Food and Drug Administration between 2001 and 2010. Jama 317, 1854-1810
11. El-Hage, W., and Surguladze, S. A. (2010). Emerging treatments in the management of bipolar disorder-focus on risperidone long acting injection. Neuropsychiatric Dis. Treat. 6, 455-464
12. Ewart, L., Dehne, E.-M., Fabre, K., Gibbs, S., Hickman, J., Hornberg, E., Ingelman-Sundberg, M., Jang, K.-J., Jones, D. R., Lauschke, V. M., et al. (2017). Application of microphysiological systems to enhance safety assessment in drug discovery. Annu. Rev. Pharmacol. Toxicol. 58, 65-82
13. Fattinger, K., Funk, C., Pantze, M., Weber, C., Reichen, J., Stieger, B., and Meier, P. J. (2001). The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: A potential mechanism for hepatic adverse reactions. Clin. Pharmacol. Ther. 69, 223-231
14. Gómez-Lechón, M. J., Tolosa, L., Conde, I., and Donato, M. T. (2014). Competency of different cell models to predict human hepatotoxic drugs. Expert Opin. Drug Metab. & Toxicol. 10, 1553-1568
15. Guo, J. J., Wigle, P. R., Lammers, K., and Vu, O. (2005). Comparison of potentially hepatotoxic drugs among major US drug compendia. Res. Social Adm. Pharm. 1, 460-479
16. Gustafsson, F., Foster, A. J., Sarda, S., Bridgland-Taylor, M. H., and Kenna, J. G. (2014). A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans. Toxicol. Sci. 137, 189-211
17. Humbert, M., Segal, E. S., Kiely, D. G., Carlsen, J., Schwierin, B., and Hoeper, M. M. (2007). Results of European postmarketing surveillance of bosentan in pulmonary hypertension. Eur. Respir. J. 30, 338-344
18. Kaplowitz, N. (2005). Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discov. 4, 489-499
19. Kenna, J. G., Stahl, S. H., Eakins, J. A., Foster, A. J., Andersson, L. C., Bergare, J., Billger, M., Elebring, M., Elmore, C. S., and Thompson, R. A. (2015). Multiple compound-related adverse properties contribute to liver injury caused by endothelin receptor antagonists. J. Pharmacol. Exp. Ther. 352, 281-290
20. Khetani, S. R., Kanchagar, C., Ukairo, O., Krzyzewski, S., Moore, A., Shi, J., Aoyama, S., Aleo, M., and Will, Y. (2013). Use of micropatterned cocultures to detect compounds that cause drug-induced liver injury in humans. Toxicol. Sci. 132, 107-117
21. Kohlroser, J., Mathai, J., Reichheld, J., Banner, B. F., and Bonkovsky, H. L. (2000). Hepatotoxicity due to troglitazone: Report of two cases and review of adverse events reported to the United States Food and Drug Administration. Am. J. Gastroenterol. 95, 272-276
22. Lasser, K. E., Allen, P. D., Woolhandler, S. J., Himmelstein, D. U., Wolfe, S. M., and Bor, D. H. (2002). Timing of new black box warnings and withdrawals for prescription medications. Jama 287, 2215-2220
23. Lauschke, V. M., Hendriks, D. F. G., Bell, C. C., Andersson, T. B., and Ingelman-Sundberg, M. (2016a). Novel 3D culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates. Chem. Res. Toxicol. 29, 1936-1955
24. Lauschke, V. M., Milani, L., and Ingelman-Sundberg, M. (2018). Pharmacogenomic biomarkers for improved drug therapyrecent progress and future developments. AAPS J. 20, 4
25. Lauschke, V. M., Vorrink, S. U., Moro, S. M. L., Rezayee, F., Nordling, é ., Hendriks, D. F. G., Bell, C. C., Sison-Young, R., Park, B. K., Goldring, C. E., et al. (2016b). Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation. Hepatology 64, 1743-1756
26. Madden, S., Spaldin, V., and Park, B. K. (1995). Clinical pharmacokinetics of tacrine. Clin. Pharmacokinet. 28, 449-457
27. Manning, F. J., and Swartz, M. (1995). Review of the Fialuridine (FIAU) Clinical Trials. National Academies Press, Washington, DC
28. Markham, L. N., Giostra, E., Hadengue, A., Rossier, M., Rebsamen, M., and Desmeules, J. (2007). Emergency liver transplantation in amodiaquine-induced fulminant hepatitis. Am. J. Trop. Med. Hyg. 77, 14-15
29. Martignoni, M., Groothuis, G. M. M., and de Kanter, R. (2006). Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin. Drug Metab. Toxicol. 2, 875-894
30. McGill, M. R., Sharpe, M. R., Williams, C. D., Taha, M., Curry, S. C., and Jaeschke, H. (2012a). The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J. Clin. Invest. 122, 1574-1583
31. McGill, M. R., Williams, C. D., Xie, Y., Ramachandran, A., and Jaeschke, H. (2012b). Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol. Appl. Pharmacol. 264, 387-394
32. McGoon, M. D., Frost, A. E., Oudiz, R. J., Badesch, D. B., Galie, N., Olschewski, H., McLaughlin, V. V., Gerber, M. J., Dufton, C., Despain, D. J., et al. (2009). Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities. Chest 135, 122-129
33. McKenzie, R., Fried, M. W., Sallie, R., Conjeevaram, H., Di Bisceglie, A. M., Park, Y., Savarese, B., Kleiner, D., Tsokos, M., Luciano, C., et al. (1995). Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N. Engl. J. Med. 333, 1099-1105
34. Murray, M., Cui, P. H., and Zhou, F. (2010). Roles of mitogenactivated protein kinases in the regulation of CYP genes. Curr. Drug Metab. 11, 850-858
35. O'Brien, P. J., Irwin, W., Diaz, D., Howard-Cofield, E., Krejsa, C. M., Slaughter, M. R., Gao, B., Kaludercic, N., Angeline, A., Bernardi, P., et al. (2006). High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening. Arch. Toxicol. 80, 580-604
36. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolaja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., et al. (2000). Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul. Toxicol. Pharmacol. 32, 56-67
37. Proctor, W. R., Foster, A. J., Vogt, J., Summers, C., Middleton, B., Pilling, M. A., Shienson, D., Kijanska, M., Strö bel, S., Kelm, J. M., et al. (2017). Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury. Arch. Toxicol. 91, 2849-2863
38. Rawden, H. C., Kokwaro, G. O., Ward, S. A., and Edwards, G. (2000). Relative contribution of cytochromes P-450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes. Br. J. Clin. Pharmacol. 49, 313-322
39. Sakatis, M. Z., Reese, M. J., Harrell, A. W., Taylor, M. A., Baines, I. A., Chen, L., Bloomer, J. C., Yang, E. Y., Ellens, H. M., Ambroso, J. L., et al. (2012). Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for 200 compounds. Chem. Res. Toxicol. 25, 2067-2082
40. Scully, L. J., Clarke, D., and Barr, R. J. (1993). Diclofenac induced hepatitis. 3 cases with features of autoimmune chronic active hepatitis. Digest. Dis. Sci. 38, 744-751
41. Sirenko, O., Hesley, J., Rusyn, I., and Cromwell, E. F. (2014). Highcontent assays for hepatotoxicity using induced pluripotent stem cell-derived cells. Assay Drug Dev. Technol. 12, 43-54
42. Sison-Young, R. L., Lauschke, V. M., Johann, E., Alexandre, E., Anthérieu, S., Aerts, H., Gerets, H. H. J., Labbe, G., Hoët, D., Dorau, M., et al. (2017). A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity. Arch. Toxicol. 91, 1385-1400
43. Suzuki, A., Andrade, R. J., Bjö rnsson, E., Lucena, M. I., Lee, W. M., Yuen, N. A., Hunt, C. M., and Freston, J. W. (2010). Drugs associated with hepatotoxicity and their reporting frequency of liver adverse events in VigiBase: Unified list based on international collaborative work. Drug Safety 33, 503-522
44. Taylor, W. R. J., and White, N. J. (2004). Antimalarial drug toxicity: A review. Drug Safety 27, 25-61
45. Tolosa, L., Pinto, S., Donato, M. T., Lahoz, A., Castell, J. V., O'Connor, J. E., and Gómez-Lechón, M. J. (2012). Development of a multiparametric cell-based protocol to screen and classify the hepatotoxicity potential of drugs. Toxicol. Sci. 127, 187-198
46. Villaverde, C., Alvarez, A. I., Redondo, P., Voces, J., Del Estal, J. L., and Prieto, J. G. (1995). Small intestinal sulphoxidation of Albendazole. Xenobiotica 25, 433-441
47. Vorrink, S. U., Ullah, S., Schmidt, S., Nandania, J., Velagapudi, V., Beck, O., Ingelman-Sundberg, M., and Lauschke, V. M. (2017). Endogenous and xenobiotic metabolic stability of primary human hepatocytes in longterm 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics. FASEB J. 31, 2696-2708
48. Ware, B. R., and Khetani, S. R. (2016). Engineered liver platforms for different phases of drug development. Trends Biotechnol. doi: 10.1016/j.tibtech.2016.08.001, 1-12
49. Waring, M. J., Arrowsmith, J., Leach, A. R., Leeson, P. D., Mandrell, S., Owen, R. M., Pairaudeau, G., Pennie, W. D., Pickett, S. D., Wang, J., et al. (2015). An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat. Rev. Drug Discov. 14, 475-486
50. Wu Chou, A. I., Lu, M.-L., and Shen, W. W. (2014). Hepatotoxicity induced by clozapine: A case report and review of literature. Neuropsychiatric Dis. Treat. 10, 1585-1587
51. Xu, J. J., Henstock, P. V., Dunn, M. C., Smith, A. R., Chabot, J. R., and de Graaf, D. (2008). Cellular imaging predictions of clinical drug-induced liver injury. Toxicol. Sci. 105, 97-105
52. Yoon, E., Babar, A., Choudhary, M., Kutner, M., and Pyrsopoulos, N. (2016). Acetaminophen-induced hepatotoxicity: A comprehensive update. J. Clin. Transl. Hepatol. 4, 131-142