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BioMed Research International
Volume 2013 (2013), Article ID 202497, 12 pages
http://dx.doi.org/10.1155/2013/202497
Research Article

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

1PharmPoint Consulting, Poolesville, MD 20837, USA
2BASF SE, Experimental Toxicology and Ecology, Z 470, D-67056 Ludwigshafen, Germany
3Metanomics GmbH, Tegeler Weg 33, 10589 Berlin, Germany
4Drug Safety Research Laboratories, Astellas Pharma Inc., Osaka, Japan
5AstraZeneca R&D, Innovative Medicines Personalised Healthcare & Biomarkers, Science for Life Laboratory, Box 1031, 17121 Solna, Sweden
6Pfizer R&D, Compound Safety Prediction, Groton, CT 06340, USA
7Drug Safety Executive Council, Needham, MA 02494, USA
8Metanomics Health GmbH, Tegeler Weg 33, 10589 Berlin, Germany
9Analytical and Bioanalytical Development, Bristol-Myers Squibb, Princeton, NJ 08543, USA

Received 23 January 2013; Revised 23 April 2013; Accepted 25 April 2013

Academic Editor: Tzung-Hai Yen

Copyright © 2013 W. B. Mattes et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. W. Brumfitt and J. M. T. Hamilton-Miller, “The changing face of chemotherapy,” Postgraduate Medical Journal, vol. 64, no. 753, pp. 552–558, 1988. View at Scopus
  2. A. T. Borchers, F. Hagie, C. L. Keen, and M. E. Gershwin, “The history and contemporary challenges of the US food and drug administration,” Clinical Therapeutics, vol. 29, no. 1, pp. 1–16, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. J. L. Stevens, “Future of toxicology—mechanisms of toxicity and drug safety: where do we go from here?” Chemical Research in Toxicology, vol. 19, no. 11, pp. 1393–1401, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. I. Kola and J. Landis, “Can the pharmaceutical industry reduce attrition rates?” Nature Reviews Drug Discovery, vol. 3, no. 8, pp. 711–715, 2004. View at Scopus
  5. E. F. Schmid, D. A. Smith, and S. W. Ryder, “Communicating the risks and benefits of medicines,” Drug Discovery Today, vol. 12, no. 9-10, pp. 355–364, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Loghman-Adham, C. I. Kiu Weber, C. Ciorciaro, J. Mann, and M. Meier, “Detection and management of nephrotoxicity during drug development,” Expert Opinion on Drug Safety, vol. 11, no. 4, pp. 581–596, 2012. View at Publisher · View at Google Scholar
  7. F. Dieterle, E. Perentes, A. Cordier et al., “Urinary clusterin, cystatin C, Β2-microglobulin and total protein as markers to detect drug-induced kidney injury,” Nature Biotechnology, vol. 28, no. 5, pp. 463–469, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. J. C. Gautier, B. Riefke, J. Walter et al., “Evaluation of novel biomarkers of nephrotoxicity in two strains of rat treated with cisplatin,” Toxicologic Pathology, vol. 38, no. 6, pp. 943–956, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. P. Y. Muller and F. Dieterle, “Tissue-specific, non-invasive toxicity biomakers: translation from preclinical safety assessment to clinical safety monitoring,” Expert Opinion on Drug Metabolism and Toxicology, vol. 5, no. 9, pp. 1023–1038, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. F. Dieterle, E. Marrer, E. Suzuki, O. Grenet, A. Cordier, and J. Vonderscher, “Monitoring kidney safety in drug development: emerging technologies and their implications,” Current Opinion in Drug Discovery and Development, vol. 11, no. 1, pp. 60–71, 2008. View at Scopus
  11. A. Bugrim, T. Nikolskaya, and Y. Nikolsky, “Early prediction of drug metabolism and toxicity: systems biology approach and modeling,” Drug Discovery Today, vol. 9, no. 3, pp. 127–135, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. D. G. Robertson, “Metabonomics in toxicology: a review,” Toxicological Sciences, vol. 85, no. 2, pp. 809–822, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. B. van Ravenzwaay, G. C. P. Cunha, E. Leibold et al., “The use of metabolomics for the discovery of new biomarkers of effect,” Toxicology Letters, vol. 172, no. 1-2, pp. 21–28, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. D. S. Wishart, “Applications of metabolomics in drug discovery and development,” Drugs in R and D, vol. 9, no. 5, pp. 307–322, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. K. J. Boudonck, M. W. Mitchell, L. Német et al., “Discovery of metabolomics biomarkers for early detection of nephrotoxicity,” Toxicologic Pathology, vol. 37, no. 3, pp. 280–292, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. R. D. Beger, J. Sun, and L. K. Schnackenberg, “Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity,” Toxicology and Applied Pharmacology, vol. 243, no. 2, pp. 154–166, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Loftus, A. Barnes, S. Ashton et al., “Metabonomic investigation of liver profiles of nonpolar metabolites obtained from alcohol-dosed rats and mice using high mass accuracy MSn analysis,” Journal of Proteome Research, vol. 10, no. 2, pp. 705–713, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. R. M. Salek, M. L. Maguire, E. Bentley et al., “A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human,” Physiological Genomics, vol. 29, no. 2, pp. 99–108, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. J. K. Nicholson, J. C. Lindon, and E. Holmes, “‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data,” Xenobiotica, vol. 29, no. 11, pp. 1181–1189, 1999. View at Scopus
  20. V. Strauss, J. Wiemer, E. Leibold et al., “Influence of strain and sex on the metabolic profile of rats in repeated dose toxicological studies,” Toxicology Letters, vol. 191, no. 1, pp. 88–95, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. W. Mellert, M. Kapp, V. Strauss et al., “Nutritional impact on the plasma metabolome of rats,” Toxicology Letters, vol. 207, no. 2, pp. 173–181, 2011. View at Publisher · View at Google Scholar
  22. M. R. Fielden, B. P. Eynon, G. Natsoulis, K. Jarnagin, D. Banas, and K. L. Kolaja, “A gene expression signature that predicts the future onset of drug-induced renal tubular toxicity,” Toxicologic Pathology, vol. 33, no. 6, pp. 675–683, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Y. Nie, M. McMillian, J. B. Parker et al., “Predictive toxicogenomics approaches reveal underlying molecular mechanisms of nongenotoxic carcinogenicity,” Molecular Carcinogenesis, vol. 45, no. 12, pp. 914–933, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. X. Fan, E. K. Lobenhofer, M. Chen et al., “Consistency of predictive signature genes and classifiers generated using different microarray platforms,” Pharmacogenomics Journal, vol. 10, no. 4, pp. 247–257, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. H. Kamp, E. Fabian, S. Groeters et al., “Application of in vivo metabolomics to preclinical/toxicological studies: case study on phenytoin-induced systemic toxicity,” Bioanalysis, vol. 4, no. 18, pp. 2291–2301, 2012. View at Publisher · View at Google Scholar
  26. National Toxicology Program, “Toxicology and carcinogenesis studies of 5,5-diphenylhydantoin (CAS No. 57-41-0) (phenytoin) in F344/N rats and B6C3F1 mice (feed studies),” National Toxicology Program Technical Report Series, vol. 404, pp. 1–303, 1993.
  27. R. Hayward and D. S. Hydock, “Doxorubicin cardiotoxicity in the rat: an in vivo characterization,” Journal of the American Association for Laboratory Animal Science, vol. 46, no. 4, pp. 20–32, 2007. View at Scopus
  28. A. Sovcikova, J. Tulinska, J. Kubova, A. Liskova, D. Syrova, and K. Horakova, “Effect of cyclosporin A in Lewis rats in vivo and HeLa cells in vitro,” Journal of Applied Toxicology, vol. 22, no. 3, pp. 153–160, 2002. View at Publisher · View at Google Scholar · View at Scopus
  29. B. Ryffel and M. J. Mihatsch, “Cyclosporine nephrotoxicity,” Toxicologic Pathology, vol. 14, no. 1, pp. 73–82, 1986. View at Scopus
  30. A. Josephine, K. Nithya, G. Amudha, C. K. Veena, S. P. Preetha, and P. Varalakshmi, “Role of sulphated polysaccharides from Sargassum Wightii in Cyclosporine A-induced oxidative liver injury in rats,” BMC Pharmacology, vol. 8, article 4, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. D. W. Cushman, F. L. Wang, W. C. Fung et al., “Comparisons in vitro, ex vivo, and in vivo of the actions of seven structurally diverse inhibitors of angiotensin converting enzyme (ACE),” The British Journal of Clinical Pharmacology, vol. 28, supplement 2, pp. 115S–131S, 1989. View at Scopus
  32. K. Imai, S. Yoshimura, T. Ohtaki, and K. Hashimoto, “One month studies on the subacute toxicity of captopril in the rats,” Journal of Toxicological Sciences, vol. 6, supplement 2, pp. 189–214, 1981. View at Scopus
  33. U. Roessner, C. Wagner, J. Kopka, R. N. Trethewey, and L. Willmitzer, “Simultaneous analysis of metabolites in potato tuber by gas chromatography-mass spectrometry,” Plant Journal, vol. 23, no. 1, pp. 131–142, 2000. View at Publisher · View at Google Scholar · View at Scopus
  34. H. Yamada, A. Yamahara, S. Yasuda et al., “Dansyl chloride derivatization of methamphetamine: a method with advantages for screening and analysis of methamphetamine in urine,” Journal of Analytical Toxicology, vol. 26, no. 1, pp. 17–22, 2002. View at Scopus
  35. B. van Ravenzwaay, M. Herold, H. Kamp et al., “Metabolomics: a tool for early detection of toxicological effects and an opportunity for biology based grouping of chemicals-from QSAR to QBAR,” Mutation Research, vol. 746, no. 2, pp. 144–150, 2012. View at Publisher · View at Google Scholar
  36. R. Looser, A. J. Krotzky, and R. N. Trethewey, “Metabolite profiling with GC-MS and LC-MS—a key tool for contemporary biology,” in Metabolome Analyses: Strategies for Systems Biology, S. Vaidyanathan, G. G. Harrigan, and R. Goodacre, Eds., pp. 103–118, Springer, New York, NY, USA, 2005.
  37. S. Yamamura, T. Hamaguchi, K. Ohoyama et al., “Topiramate and zonisamide prevent paradoxical intoxication induced by carbamazepine and phenytoin,” Epilepsy Research, vol. 84, no. 2-3, pp. 172–186, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. M. D. Evered and M. M. Robinson, “Increased or decreased thirst caused by inhibition of angiotensin-converting enzyme in the rat,” Journal of Physiology, vol. 348, pp. 573–588, 1984. View at Scopus
  39. M. D. Evered and M. M. Robinson, “The renin-angiotensin system in drinking and cardiovascular responses to isoprenaline in the rat,” Journal of Physiology, vol. 316, pp. 357–367, 1981. View at Scopus
  40. G. Minotti, P. Menna, E. Salvatorelli, G. Cairo, and L. Gianni, “Anthracyclines: molecular advances and pharmacologie developments in antitumor activity and cardiotoxicity,” Pharmacological Reviews, vol. 56, no. 2, pp. 185–229, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. S. Chitturi and J. George, “Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs,” Seminars in Liver Disease, vol. 22, no. 2, pp. 169–183, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. E. Bjornsson, “Hepatotoxicity associated with antiepileptic drugs,” Acta Neurologica Scandinavica, vol. 118, no. 5, pp. 281–290, 2008.
  43. M. W. Russo, J. A. Galanko, R. Shrestha, M. W. Fried, and P. Watkins, “Liver transplantation for acute liver failure from drug induced liver injury in the United States,” Liver Transplantation, vol. 10, no. 8, pp. 1018–1023, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. K. E. L. McColl, M. R. Moore, G. G. Thompson, and A. Goldberg, “Induction of δ-aminolevulinic acid synthase in leukocytes of patients on phenytoin therapy: comparison with changes in rat hepatic tissue,” The British Journal of Clinical Pharmacology, vol. 9, no. 4, pp. 327–331, 1980. View at Scopus
  45. J. W. Jung, J. S. Park, J. W. Hwang et al., “Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray,” Journal of Veterinary Medical Science, vol. 66, no. 11, pp. 1329–1333, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. Q. Huang, X. Jin, E. T. Gaillard et al., “Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants,” Mutation Research, vol. 549, no. 1-2, pp. 147–167, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. R. J. Andrade, M. I. Lucena, N. Kaplowitz et al., “Outcome of acute idiosyncratic drug-induced liver injury: long-term follow-up in a hepatotoxicity registry,” Hepatology, vol. 44, no. 6, pp. 1581–1588, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. T. R. Helliwell, J. H. K. Yeung, and B. K. Park, “Hepatic necrosis and glutathione depletion in captopril-treated mice,” The British Journal of Experimental Pathology, vol. 66, no. 1, pp. 67–78, 1985. View at Scopus
  49. M. Kurus, M. Esrefoglu, G. Sogutlu, and A. Atasever, “Melatonin prevents cyclosporine-induced hepatotoxicity in rats,” Medical Principles and Practice, vol. 18, no. 5, pp. 407–410, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. K. V. Kowdley and E. B. Keeffe, “Hepatotoxicity of transplant immunosuppressive agents,” Gastroenterology Clinics of North America, vol. 24, no. 4, pp. 991–1001, 1995. View at Scopus
  51. W. M. Bennett and D. J. Norman, “Action and toxicity of cyclosporine,” Annual Review of Medicine, vol. 37, pp. 215–224, 1986. View at Scopus
  52. R. Danesi and M. Del Tacca, “Hematologic toxicity of immunosuppressive treatment,” Transplantation Proceedings, vol. 36, no. 3, pp. 703–704, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Rahman, J. Treat, J. K. Roh et al., “A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin,” Journal of Clinical Oncology, vol. 8, no. 6, pp. 1093–1100, 1990. View at Scopus
  54. O. Al-Shabanah, M. Mansour, H. El-Kashef, and A. Al-Bekairi, “Captopril ameliorates myocardial and hematological toxicities induced by adriamycin,” Biochemistry and Molecular Biology International, vol. 45, no. 2, pp. 419–427, 1998. View at Scopus
  55. A. Aviles, J. Herrera, E. Ramos, R. Ambriz, J. Aguirre, and J. Pizzuto, “Hepatic injury during doxorubicin therapy,” Archives of Pathology and Laboratory Medicine, vol. 108, no. 11, pp. 912–913, 1984. View at Scopus
  56. H. I. El-Sayyad, M. F. Ismail, F. M. Shalaby et al., “Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats,” International Journal of Biological Sciences, vol. 5, no. 5, pp. 466–473, 2009. View at Scopus
  57. P. I. Pillans and A. Koopowitz, “Captopril-associated agranulocytosis. A report of 3 cases,” South African Medical Journal, vol. 79, no. 7, pp. 399–400, 1991. View at Scopus
  58. Y. Chen, X. Zheng, R. Zou, and J. Wang, “Effects of cyclosporin-a on rat skeletal biomechanical properties,” BMC Musculoskeletal Disorders, vol. 12, article 240, 2011.
  59. C. Movsowitz, S. Epstein, M. Fallon, F. Ismail, and S. Thomas, “Cyclosporin-A in vivo produces severe osteopenia in the rat: effect of dose and duration of administration,” Endocrinology, vol. 123, no. 5, pp. 2571–2577, 1988. View at Scopus
  60. A. Aroldi, A. Tarantino, G. Montagnino, B. Cesana, C. Cocucci, and C. Ponticelli, “Effects of three immunosuppressive regimens on vertebral bone density in renal transplant recipients: a prospective study,” Transplantation, vol. 63, no. 3, pp. 380–386, 1997. View at Publisher · View at Google Scholar · View at Scopus
  61. F. Zannad, L. Bray-Desboscs, R. El Ghawi, M. Donner, E. Thibout, and J. F. Stoltz, “Effects of lisinopril and hydrochlorothiazide on platelet function and blood rheology in essential hypertension: a randomly allocated double-blind study,” Journal of Hypertension, vol. 11, no. 5, pp. 559–564, 1993. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Gill, V. Fonseca, P. Dandona, and J. Y. Jeremy, “Lisinopril and nifedipine administration inhibits the ex vivo uptake of [45Ca2+] by platelets from hypertensive diabetic patients,” The British Journal of Clinical Pharmacology, vol. 33, no. 2, pp. 161–165, 1992. View at Scopus
  63. B. N. M. Zordoky, A. Anwar-Mohamed, M. E. Aboutabl, and A. O. S. El-Kadi, “Acute doxorubicin toxicity differentially alters cytochrome P450 expression and arachidonic acid metabolism in rat kidney and liver,” Drug Metabolism and Disposition, vol. 39, no. 8, pp. 1440–1450, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Y. Chang and T. D. Schiano, “Review article: drug hepatotoxicity,” Alimentary Pharmacology and Therapeutics, vol. 25, no. 10, pp. 1135–1151, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. H. Dodiya, M. Jain, and S. S. Goswami, “Renal toxicity of lisinopril and rosuvastatin, alone and in combination, in wistar rats,” International Journal of Toxicology, vol. 30, no. 5, pp. 518–527, 2011. View at Publisher · View at Google Scholar
  66. E. Saltiel and W. McGuire, “Doxorubicin (Adriamycin) cardiomyopathy. A critical review,” Western Journal of Medicine, vol. 139, no. 3, pp. 332–341, 1983. View at Scopus
  67. D. G. Robertson, P. B. Watkins, and M. D. Reily, “Metabolomics in toxicology: preclinical and clinical applications,” Toxicological Sciences, vol. 120, supplement 1, pp. S146–S170, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. D. G. Robertson, M. D. Reily, J. C. Lindon, E. Holmes, and J. K. Nicholson, “Metabonomic technology as a tool for rapid throughput in vivo toxicity screening,” in Cellular and Molecular Toxicology, J. P. V. Heuvel, G. H. Perdew, W. B. Mattes, and W. F. Greenlee, Eds., vol. 14, pp. 583–610, Elsevier, Amsterdam, The Netherlands, 2002.
  69. J. G. Bundy, J. K. Sidhu, F. Rana et al., “‘Systems toxicology’ approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus,” BMC Biology, vol. 6, article 25, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Takei, Y. Ando, W. Saitoh et al., “Ethylene glycol monomethyl ether-induced toxicity is mediated through the inhibition of flavoprotein dehydrogenase enzyme family,” Toxicological Sciences, vol. 118, no. 2, Article ID kfq211, pp. 643–652, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. T. M. D. Ebbels, H. C. Keun, O. P. Beckonert et al., “Prediction and classification of drug toxicity using probabilistic modeling of temporal metabolic data: the consortium on metabonomic toxicology screening approach,” Journal of Proteome Research, vol. 6, no. 11, pp. 4407–4422, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. J. D. Vassallo, S. M. Hicks, G. P. Daston, and L. D. Lehman-McKeeman, “Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity,” Toxicological Sciences, vol. 80, no. 2, pp. 249–257, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Schwerin, U. Dorroch, M. Beyer, H. Swalve, C. C. Metges, and P. Junghans, “Dietary protein modifies hepatic gene expression associated with oxidative stress responsiveness in growing pigs,” The FASEB Journal, vol. 16, no. 10, pp. 1322–1324, 2002. View at Scopus
  74. J. P. Luyendyk, W. B. Mattes, L. D. Burgoon et al., “Gene expression analysis points to hemostasis in livers of rats cotreated with lipopolysaccharide and ranitidine,” Toxicological Sciences, vol. 80, no. 1, pp. 203–213, 2004. View at Publisher · View at Google Scholar · View at Scopus