Cellular imaging predictions of clinical drug-induced liver injury

Toxicological Sciences

Volumn 105, Issue 1, 2008, Pages 97-105

  Xu, Jinghai J ^a,b   Henstock, Peter V ^a   Dunn, Margaret C ^a   Smith, Arthur R ^a   Chabot, Jeffrey R ^a   de Graaf, David ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Hepatitis; Hepatotoxicity testing; Idiosyncratic hepatotoxicity; In vitro in vivo correlations; Liver injury; Mechanism of organ toxicity; Pharmacokinetic scaling

Indexed keywords

ACETYLSALICYLIC ACID; AMITRIPTYLINE; CHLORZOXAZONE; DANTROLENE; DICLOFENAC; FAMOTIDINE; FLUOXETINE; GLUTATHIONE; KETOTIFEN; LABETALOL; MELATONIN; NADOLOL; NEFAZODONE; NIMESULIDE; PAROMOMYCIN; PENICILLIN G; PERHEXILINE; PIOGLITAZONE; PRIMIDONE; PROPRANOLOL; ROSIGLITAZONE; SIMVASTATIN; SULINDAC; SUMATRIPTAN; TACRINE; TELITHROMYCIN; TETRACYCLINE; TROGLITAZONE; UNINDEXED DRUG; ZILEUTON;

ARTICLE; CELL LEVEL; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG CYTOTOXICITY; DRUG INDUCED DISEASE; FALSE POSITIVE RESULT; HUMAN; HUMAN CELL; IMAGE QUALITY; IMAGING SYSTEM; IN VITRO STUDY; LIVER CELL; LIVER CELL CULTURE; LIVER INJURY; LIVER TOXICITY; NONHUMAN; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PREDICTION; TOXICITY TESTING;

CELLS, CULTURED; DATABASES AS TOPIC; FALSE POSITIVE REACTIONS; HEPATOCYTES; HUMANS; MITOCHONDRIA, LIVER; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS; ROC CURVE;

ANIMALIA;

EID: 49249103327     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfn109     Document Type: Article

References (64)

1. Aithal, G. P., and Day, C. P. (2007). Nonsteroidal anti-inflammatory drug-induced hepatotoxicity. Clin. Liver Dis. 11, 563-575.
2. Berson, A., De Beco, V., Letteron, P., Robin, M. A., Moreau, C., El Kahwaji, J., Verthier, N., Feldmann, G., Fromenty, B., and Pessayre, D. (1998). Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology 114 764-774.
3. Bi, Y. A., Kazolias, D., and Duignan, D. B. (2006). Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport. Drug Metab. Dispos. 34, 1658-1665.
4. Boelsterli, U. A. (2002). Mechanisms of NSAID-induced hepatotoxicity: Focus on nimesulide. Drug Saf. 25(9), 633-648.
5. Boelsterli, U. A., and Lim, P. L. (2007). Mitochondrial abnormalities - A link to idiosyncratic drug hepatotoxicity? Toxicol. Appl. Pharmacol. 220, 92-107.
6. Breiman, L. (2001). Random forests. Machine Learn. 45, 5-32.
7. Chen, Q., Ngui, J. S., Doss, G. A., Wang, R. W., Cai, X., DiNinno, F. P., Blizzard, T. A., Hammond, M. L., Steams, R. A., Evans, D. C., Baillie, T. A., and Tang, W. (2002). Cytochrome P450 3A4-mediated bioactivation of raloxifene: Irreversible enzyme inhibition and thiol adduct formation. Chem. Res. Toxicol. 15, 907-914.
8. Choi, J., and Ou, J. H. (2006). Mechanisms of liver injury. III. Oxidative stress in the pathogenesis of hepatitis C virus. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G847-G851.
9. Choi, S. (2003). Nefazodone (Serzone) withdrawn because of hepatotoxicity. CMAJ 169, 1187.
10. Davila, J. C., Xu, J. J., Hoffmaster, K. A., O'Brien, P. J., and Strom, S. C. (2007). Chapter 1. Current in vitro systems used to address drug-induced liver injury. In Hepatotoxicity: From Genomics to In vitro and In Vivo (S. Sahu, Ed.). Wiley & Sons, New York.
11. Dome, J. L., Walton, K., and Renwick, A. G. (2005). Human variability in xenobiotic metabolism and pathway-related uncertainty factors for chemical risk assessment: A review. Food Chem. Toxicol. 43, 203-216.
12. Duda, P. O., Hart, P. E., Marroquin, L. D., Nadanaciva, S., Xu, J. J., Dunn, M. C., Smith, A. R., and Will, Y. (2000). In Pattern Classification. Wiley, New York.
13. Dykens, J. A., Jamieson, J. D., Marroquin, L. D., Nadanaciva, S., Xu, J. J., Dunn, M. C., Smith, A. R., and Will, Y. (2008). In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone and buspirone. Toxicol. Sci. doi: 10.1093/toxsci/kfn56.
14. EMEA. (2008). Non-clinical guideline on drug-induced hepatotoxicity. Available at: http://www.emea.europa.eu/pdfs/human/swp/15011506en.pdf.
15. FDA. (2007). Drug-induced liver injury: Premarketing clinical evaluation. Available at: http://www.fda.gov/Cder/guidance/7507dft.htm.
16. Gilisteo, M., Rissel, M., Sergent, O., Chevanne, M., Cillard, J., Guillouzo, A., and Lagadic-Gossmann, D. (2000). Hepatotoxicity of tacrine: Occurrence of membrane fluidity alterations without involvement of lipid peroxidation. J. Pharmacol. Exp. Ther. 294, 160-167.
17. Giacomini, K. M., Krauss, R. M., Roden, D. M., Eichelbaum, M., Hayden, M. R., and Nakamura, Y. (2007). When good drugs go bad. Nature 446, 975-977.
18. Gross-Steinmeyer, K., Stapleton, P. L., Tracy, J. H., Bammler, T. K., Lehman, T., Strom, S. C., and Eaton, D. L. (2005). Influence of Matrigel-overlay on constitutive and inducible expression of nine genes encoding drug-metabolizing enzymes in primary human hepatocytes. Xenobiotica 35, 419-438.
19. Guggenheim, K. Y. (1993). Paracelsus and the science of nutrition in the renaissance. On occasion of the 500th anniversary of his birth. J. Nutr 123, 1189-1194.
20. Hewitt, N. J., Lechon, M. J., Houston, J. B., Hallifax, D., Brown, H. S., Maurel, P., Kenna, J. G., Gustavsson, L., Lohmann, C., Skonberg, C., et al. (2007). Primary hepatocytes: Current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab. Rev. 39, 159-234.
21. Hoffmaster, K. A., Tumcliff, R. Z., LeCluyse, E. L., Kim, R. B., Meier, P. J., and Brouwer, K. L. (2004). P-glycoprotein expression, localization, and function in sandwich-cultured primary rat and human hepatocytes: Relevance to the hepatobiliary disposition of a model opioid peptide. Pharm. Res. 21, 1294-1302.
22. Holownia, A., and Braszko, J. J. (2004). Tamoxifen cytotoxicity in hepatoblastoma cells stably transfected with human CYP3A4. Biochem. Pharmacol. 67, 1057-1064.
23. Holt, M. P., and Ju, C. (2006). Mechanisms of drug-induced liver injury. AAPS J. 8(1), E48-E54.
24. Ito, K., Chiba, K., Horikawa, M., Ishigami, M., Mizuno, N., Aoki, J., Gotoh, Y., Iwatsubo, T., Kanamitsu, S., Kato, M., et al. (2002). Which concentration of the inhibitor should be used to predict in vivo drug interactions from in vitro data? AAPS Pharm. Sci. 4 (4), E25.
25. Kalgutkar, A. S., et al. (2005). Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4. Drug Metab. Dispos. 33, 243-253.
26. Kaplowitz, N. (2005). Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discov. 4, 489-499.
27. Kasdallah-Grissa, A., Momagui, B., Aouani, E., Hammami, M., El May, M., Gharbi, N., Kamoun, A., and El-Fazaa, S. (2007). Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver. Life Sci. 80, 1033-1039.
28. Kass, G. E. N., and Price, S. C. (2008). Role of mitochondria in drug-induced cholestatic injury. Clin. Liver Dis. 12, 27-51.
29. Kirkland, D., Pfuhler, S., Tweats, D., Aardema, M., Corvi, R., Darroudi, F., Elhajouji, A., Glatt, H., Hastwell, P., Hayashi, M., et al. (2007). How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: Report of an ECVAM Workshop. Mutat. Res. 628, 31-55.
30. Kostrubsky, S. E., Strom, S. C., Kalgutkar, A. S., Kulkarni, S., Atherton, J., Mireles, R., Feng, B., Kubik, R., Hanson, J., Urda, E., et al. (2006). Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. Toxicol. Sci. 90, 451-459.
31. Lasko, T. A., Bhagwat, J. G., Zou, K. H., and Ohno-Machado, L. (2005). The use of receiver operating characteristic curves in biomedical informatics. J. Biomed. Inform. 38, 404-415.
32. Lavílle, N., Ait-Aissa, S., Gomez, E., Casellas, C., and Porcher, J. M. (2004). Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes. Toxicology 196 41-55.
33. LeCluyse, E. L., Alexandre, E., Hamilton, G. A., Viollon-Abadie, C., Coon, D. J., Jolley, S., and Richert, L. (2005). Isolation and culture of primary human hepatocytes. Methods Mol. Biol. 290, 207-229.
34. Lee, W. M. (2003). Drug-induced hepatotoxicity. N. Engl. J. Med. 349, 474-485.
35. Lee, W. M., and Senior, J. R. (2005). Recognizing drug-induced liver injury: Current problems, possible solutions. Toxicol. Pathol. 33, 155-164.
36. Li, A. P. (2002). A review of the common properties of drugs with idiosyncratic hepatotoxicity and the "multiple determinant hypothesis" for the manifestation of idiosyncratic drug toxicity. Chem. Biol. Interact. 142, 7-23.
37. Navarro, V. J., and Senior, J. R. (2006). Drug-related hepatotoxicity. N. Engl. J. Med. 354, 731-739.
38. 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.
39. 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.
40. Page, J. L., Johnson, M. C., Olsavsky, K. M., Strom, S. C., Zarbl, H., and Omiecinski, C. J. (2007). Gene expression profiling of extracellular matrix as an effector of human hepatocyte phenotype in primary cell culture. Toxicol. Sci. 97, 394-397.
41. Pessayre, D., Mansouri, A., Haouzi, D., and Fromenty, B. (1999). Hepatotoxicity due to mitochondrial dysfunction. Cell Biol. Toxicol. 15, 367-373.
42. Powers, J. (2007). SBIR conference. Available at: http://grants.nih.gov/ grants/funding/SBIRConf2007/SBIRConf2007_%20Powers.ppt [accessed May 28th, 2007] (No events in 3000 patients rules out risk of 1:1000 [compared to background hepatotoxicity risk of 1:1,000,000]).
43. Ross, D. B. (2007). The FDA and the case of Ketek. N. Engl. J. Med. 356(16), 1601-1604.
44. Routledge, P. A., O'Mahony, M. S., and Woodhouse, K. W. (2004). Adverse drug reactions in elderly patients. Br. J. Clin. Pharmacol. 57 121-126.
45. Saravanan, N., Rajasankar, S., and Nalini, N. (2007). Antioxidant effect of 2-hydroxy-4-methoxy benzoic acid on ethanol-induced hepatotoxicity in rats. J. Pharm. Pharmacol. 59, 445-453.
46. Scheen, A. J. (2001). Thiazolidinediones and liver toxicity. Diabetes Metab. 27, 305-313.
47. Schuster, D., Laggner, C., and Langer, T. (2005). Why drugs fail - a study on side effects in new chemical entities. Curr. Pharm. Des. 11(27), 3545-3559.
48. Senior, J. R. (2007). Drug hepatotoxicity from a regulatory perspective. Clin. Liver Dis. 11, 507-524.
49. Shah, R. R. (2006). Can pharmacogenetics help rescue drugs withdrawn from the market? Pharmacogenomics 7, 889-908.
50. Singh, Y. N. (2005). Potential for interaction of kava and St. John's wort with drugs. J. Ethnopharmacol., 100(1-2), 108-113.
51. Sokol, R. J., Devereaux, M., Dahl, R., and Gumpricht, E. (2006). Let there be bile" - Understanding hepatic injury in cholestasis. J. Pediatr. Gastroenterol. Nutr. 43(Suppl. 1), S4-S9.
52. Stricker, B. H. C. Ed. (1992). In Drug-Induced Hepatic Injury. Elsevier, Amsterdam.
53. Tavintharan, S., Ong, C. N., Jeyaseelan, K., Sivakumar, M., Lim, S. C., and Sum, C. F. (2007). Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity? Toxicol. Appl. Pharmacol. 223 173-179.
54. Temple, R. (2006). Hy's law: Predicting serious hepatotoxicity. Pharmacoepidemiol. Drug Saf. 15, 241-243.
55. Temple, R. J. (2001). Hepatotoxicity through the Years Impact on the FDA. Drug-induced liver toxicity. Silver Spring, MD Available at: http://www.fda.gov/cder/livertox/Presentations/im1389/sld003.htm. Accessed June 13, 2008.
56. Thiim, M., and Friedman, L. S. (2003). Hepatotoxicity of antibiotics and antifungals. Clin. Liver Dis. 7, 381-399; vi-vii.
57. Uetrecht, J. (2008). Idiosyncratic drug reactions: Past, present, and future. Chem. Res. Toxicol. 21, 84-92.
58. Ulrich, R. G. (2007), Idiosyncratic toxicity: A convergence of risk factors. Annu. Rev. Med. 58, 17-34.
59. Watkins, P. B. (2005). Idiosyncratic liver injury: Challenges and approaches. Toxicol. Pathol. 33, 1-5.
60. Xu, I., Ma, M., and Purcell, W. M. (2003). Characterisation of some cytotoxic endpoints using rat liver and HepG2 spheroids as in vitro models and their application in hepatotoxicity studies. II. Spheroid cell spreading inhibition as a new cytotoxic marker. Toxicol. Appl. Pharmacol. 189, 112-119.
61. Xu, J. J., Diaz, D., and O'Brien, P. J. (2004). Applications of cytotoxicity assays and pre-lethal mechanistic assays for assessment of human hepatotoxicity potential. Chem. Biol. Interact. 150, 115-128.
62. Zhao, S. X., Dalvie, D. K., Kelly, J. M., Soglia, J. R., Frederick, K. S., Smith, E. B., Obach, R. S., and Kalgutkar, A. S. (2007). NADPH-dependent covalent binding of [3H]paroxetine to human liver microsomes and S-9 fractions: Identification of an electrophilic quinone metabolite of paroxetine. Chem. Res. Toxicol. 20, 1649-1657.
63. Zimmerman, H. (1999). In Hepatotoxicity: The Adverse Effects of Drugs and other Chemicals on the Liver. Lippincott Williams & Wilkins, Philadelphia, PA.
64. Zimmerman, H. J. (2000). Drug-induced liver disease. Clin. Liver Dis. 4(1), 73-96, vi.