Investigation of the hepatotoxicity of flutamide: Pro-survival/apoptotic and necrotic switch in primary rat hepatocytes characterized by metabolic and transcriptomic profiles in microfluidic liver biochips

Toxicology in Vitro

Volumn 28, Issue 5, 2014, Pages 1075-1087

  Legendre, Audrey ^a   Jacques, Sébastien ^b   Dumont, Florent ^b   Cotton, JérÔme ^c   Paullier, Patrick ^a   Fleury, Marie José ^a   Leclerc, Eric ^a  

^a UNIVERSITÉ DE TECHNOLOGIE DE COMPIÈGNE   (France)

^b INSTITUT COCHIN   (France)

^c Profilomic   (France)

Author keywords

Flutamide; Hepatotoxicity; Metabolism; Microarray; Microfluidic biochips; Rat primary hepatocytes; Transcriptomic

Indexed keywords

FLUTAMIDE; FLUTAMIDE GLUTHATIONE; HYDROXYFLUTAMIDE; HYDROXYFLUTAMIDE GLUTHATIONE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; UNCLASSIFIED DRUG; ANTIANDROGEN; CYTOCHROME P450 1A1; MESSENGER RNA;

AMINO ACID METABOLISM; ANIMAL CELL; APOPTOSIS; ARTICLE; BCL2 GENE; BIOCHIP; BIOTRANSFORMATION; CELL AGGREGATION; CELL DEATH; CELL DIFFERENTIATION; CELL SURVIVAL; CELL VIABILITY; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CREB5 GENE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOWN REGULATION; FATTY ACID METABOLISM; GENE; GENE EXPRESSION; IGF GENE; IKBKG GENE; IN VITRO STUDY; IN VIVO STUDY; LIPID METABOLISM; LIVER CELL; LIVER INJURY; LIVER TOXICITY; MICROARRAY ANALYSIS; MITOCHONDRIAL PERTURBATION; NONHUMAN; PDGFD GENE; PHENOTYPE; RAT; SIGNAL TRANSDUCTION; TIGHT JUNCTION; UPREGULATION; ANIMAL; BIOREACTOR; CELL CULTURE; DRUG EFFECTS; GENE EXPRESSION PROFILING; METABOLISM; MICROFLUIDIC ANALYSIS; TOXICITY;

ANDROGEN ANTAGONISTS; ANIMALS; BIOREACTORS; CELLS, CULTURED; CYTOCHROME P-450 CYP1A1; FLUTAMIDE; GENE EXPRESSION PROFILING; HEPATOCYTES; MICROARRAY ANALYSIS; MICROFLUIDIC ANALYTICAL TECHNIQUES; RATS; RNA, MESSENGER;

EID: 84901375338     PISSN: 08872333     EISSN: 18793177     Source Type: Journal    
DOI: 10.1016/j.tiv.2014.04.008     Document Type: Article

References (48)

1. Aizawa Y., Ikemoto I., Kishimoto K., Wada T., Yamazaki H., Ohishi Y., Kiyota H., Furuta N., Suzuki H., Ueda M. Flutamide-induced hepatic dysfunction in relation to steady-state plasma concentrations of flutamide and its metabolites. Mol. Cell. Biochem. 2003, 252:149-156.
2. Alaynick W. Nuclear receptors, mitochondria and lipid metabolism. Mitochondrion 2008, 8:329-337.
3. Anderson S., Dunn C., Laughter A., Yoon L., Swanson C., Stulnig T., Steffensen K., Chandraratna R., Gustafsson J., Corton C. Overlapping transcriptional programs regulated by the nuclear receptors peroxisome proliferator-activated receptor, retinoid X receptor, and liver X receptor in mouse liver. Mol. Pharmacol. 2004, 66:1440-1452.
4. Anjum S., Swan S.K., Lambrecht L.J., Radwanski E., Cutler D.L., Affrime M.B., Halstenson C.E. Pharmacokinetics of flutamide in patients with renal insufficiency. Br. J. Clin. Pharmacol. 1999, 47:43-47.
5. Bains W. Failure rates in drug discovery and development: will we ever get any better? drug discovery world fall 2004. Business 2004, 1-18.
6. Baudoin R., Griscom L., Prot J.M., Legallais C., Leclerc E. Behavior of HepG2/C3A cell cultures in a microfluidic bioreactor. Biochem. Eng. J. 2011, 53:172-181.
7. Baudoin R., Alberto G., Legallais C., Leclerc E. Parallelized microfluidic biochips in multi well plate applied to liver tissue engineering. Sensor Actuator B 2012, 173:919-926.
8. Baudoin R., Prot J.M., Nicolas G., Brocheton J., Brochot C., Legallais C., Benech H., Leclerc E. Evaluation of seven drug metabolism and clearances by cryopreserved Human primary hepatocytes cultivated in microfluidic biochips. Xenobiotica 2013, 43:140-152.
9. Baudoin R., Legendre A., Jacques S., Cotton J., Bois F., Leclerc E. Evaluation of a liver microfluidic biochip to predict in vivo clearances of seven drugs in rats. J. Pharm. Sci. 2014, 103:706-718.
10. Chao P., Maguire T., Novik E., Cheng K.C., Yarmush M.L. Evaluation of a microfluidic based cell culture platform with primary human hepatocytes for the prediction of hepatic clearance in human. Biochem. Pharmacol. 2009, 78:625-632.
11. Cabrero A., Laguna J.C., Vázquez M. Peroxisome proliferator-activated receptors and the control of inflammation. Curr. Drug. Targets Inflamm. Allergy. 2002, 1:243-248.
12. Cheng S., Prot J.M., Leclerc E., Bois F.Y. Zonation-related pathways in human hepatocellular carcinoma cells in dynamic vs. static culture microenvironments. BMC Genom. 2012, 13:54-64.
13. Choucha-Snouber L., Letourneur F., Chafey P., Broussard C., Monge M., Legallais C., Leclerc E. Analysis of transcriptomic and proteomic profiles demonstrates the improvement of the MDCK cell function in a renal microfluidic biochip. Biotechnol. Prog. 2012, 28:474-484.
14. Choucha-Snouber L., Aninat C., Grsicom L., Madalinski G., Brochot C., Poleni P.E., Razan F., Guguen Guillouzo C., Legallais C., Corlu A., Leclerc E. Investigation of ifosfamide nephrotoxicity induced in a liver kidney co-culture biochip. Biotechnol. Bioeng. 2013, 110:597-608.
15. Choucha-Snouber L., Bunescu A., Legallais C., Brochot C., Dumas M.E., Elena-Herrmann B., Leclerc E. Metabolomics-on-a-chip of hepatotoxicity induced by anticancer drug flutamide and its active metabolite hydroxyflutamide using HepG2/C3a microfluidic biochips. Toxicol. Sci. 2013, 132:8-20.
16. Coe K., Jiav Y., Ho H., Rademacher P., Bammler T., Beyer R., Farin F., Woodke L., Stephen R., Plymate S., Fausto N., Nelson S. Comparison of the cytotoxicity of the nitroaromatic drug flutamide to its cyano analogue in the hepatocyte cell line TAMH: evidence for complex I inhibition and mitochondrial dysfunction using toxicogenomic screening. Chem. Res. Toxicol. 2007, 20:1277-1290.
17. Coe K., Nelson S., Ulrich R., He Y., Dai X., Cheng O., Caguyong M., Roberts C., Slatter G. Profiling the hepatic effects of flutamide in rats: a microarray comparison with classical aryl hydrocarbon receptor lignads and atypical CYP1A inducers. Drug Metab. Dispo. 2006, 34:1266-1275.
18. Degli Esposti D., Hamelin J., Bosselut N., Saffroy R., Sebagh M., Pommier A., Martel C., Lemoine A. Mitochondrial roles and cytoprotection in chronic liver injury. Biochem. Res. Int. 2012, 1-16. ID 387626.
19. Fraczek J., Bolleyn J., Vanhaecke T., Rogiers V., Vinken M. Primary hepatocyte cultures for pharmaco-toxicological studies: at the busy crossroad of various anti-dedifferentiation strategies. Arch. Toxicol. 2013, 87:577-610.
20. Fulda S., Gorman A., Hori Osamu, Samali A. Cellular stress response: cell survival and cell death. Int. J. Cell Biol. 2010, 5:1-23.
21. Gonzalez R.J., Tarloff J.B. Evaluation of hepatic subcellular fractions for Alamar blue and MTT reductase activity. Toxicol. In Vitro 2001, 15:257-259.
22. Iwanaga T., Nakakariya M., Yabuuchi H., Maeda T., Tamai I. Involvement of bile salt export pump in flutamide-induced cholestatic hepatitis. Biol. Pharm. Bull. 2007, 30:739-744.
23. Kashimshetty R., Desai V.G., Kale V.M., Lee T., Moland C.L., Branham W.S., New L.S., Chan E.C., Younis H., Boelsterli U.A. Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity. Toxicol. Appl. Pharmacol. 2009, 238:150-159.
24. Kostrubsky S.E., Strom S.C., Ellis E., Nelson S.D., Mutlib A.E. Transport, metabolism, and hepatotoxicity of flutamide, drug-drug interaction with acetaminophen involving phase I and phase II metabolites. Chem. Res. Toxicol. 2007, 20:1503e12.
25. Legendre A., Baudoin R., Alberto G., Paullier P., Naudot M., Bricks T., Brocheton J., Jacques S., Cotton J., Leclerc E. Metabolic characterization of primary rat hepatocytes cultivated in parallel microfluidic biochips. J. Pharm. Sci. 2013, 102:3264-3276.
26. Matsuzaki Y., Nagai D., Ichimura E., Goda R., Tomura A., Doi M., Nishikawa K. Metabolism and hepatic toxicity of flutamide in cytochrome P450 1A2 knockout SV129 mice. J. Gastroenterol. 2006, 41:231-239.
27. Mehta R., Chan K., Lee O., Tafazoli S., Obrien P. Drug associated mitochondrial toxicity. Drug-Induced Mitochondrial Dysfunction 2008, Yvonne Will. J.A. Dykens (Ed.).
28. Morten K., Badder L., Knowles H. Differential regulation of HIF-mediated pathways increases mitochondrial metabolism and ATP production in hypoxic osteoclasts. J. Pathol. 2013, 229:755-764.
29. Naftalin R., Afzal I., Cunningham P., Halai M., Ross C., Salleh N., Milligan S. Interactions of androgens, green tea catechins and the antiandrogen flutamide with the external glucose-binding site of the, human erythrocyte glucose transporter GLUT1. Br. J. Pharmacol. 2003, 140:487-499.
30. Novik E., Maguire T.J., Chao P., Cheng K.C., Yarmush M.L. A microfluidic hepatic coculture platform for cell-based drug metabolism studies. Biochem. Pharmacol. 2010, 79:1036-1044.
31. Petrenko Y.A., Gorokhova N.A., Tkachova E.N., Petrenko A.Y. The reduction of Alamar Blue by peripheral blood lymphocytes and isolated mitochondria. Ukr. Biokhim. Zh. 2005, 77:100-105.
32. Powers M.J., Janigan D., Wack K.E., Baker Stolz D.B., Griffith L. Functional behavior of primary Rat liver cells in a three-dimensional perfused microarray bioreactor. Tissue Eng. 2002, 8:499-508.
33. Prot J.M., Briffaut A.S., Letourneur F., Chafey P., Merlier F., Grandvalet Y., Legallais C., Leclerc E. Integrated proteomic and transcriptomic investigation highlights original insight into paracetamol toxicity in liver biochip. PlosOne 2011, 6:21268.
34. Prot J.M., Aninat C., Griscom L., Razan F., Brochot C., Guguen Guillouzo C., Legallais C., Corlu A., Leclerc E. Improvement of HepG2/C3a cell functions in a microfluidic biochip. Biotechnol. Bioeng. 2011, 108:1704-1715.
35. Prot J.M., Bunescu A., Elena-Hermann B., Aninat C., Choucha Snouber L., Griscom L., Bois F., Legallais C., Brochot C., Corlu A., Dumas M.D., Leclerc E. Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol. Appl. Pharma. 2012, 259:270-280.
36. Radwanski E., Perentesis G., Symchowicz S., Zampaglione N. Single and multiple dose pharmacokinetic evaluation of flutamide in normal geriatric volunteers. J. Clin. Pharmacol. 1989, 29:554-558.
37. 2+-dependent apoptosis and necrosis. Cell Calcium 2011, 50:222-233.
38. Sakuma T., Ohtake M., Katsurayama Y., Jarukamjorn K., Nemuto N. Induction of CYP1A2 by Phenobarbital in the Livers of Aryl Hydrocarbon-Responsive and -Nonresponsive. Mice Drug Metab. Dispo. 1999, 27:379-384.
39. Schulz M., Schmoldt A., Donn F., Becker H. The pharmacokinetics of flutamide and its major metabolites after a single oral dose and during chronic treatment. Eur. J. Clin. Pharmacol. 1988, 34:633-636.
40. Shet M., Mc Paul M., Fisher C., Stallings N., Estabrook R. Metabolism of the antiandrogenic drug (flutamide) by human CYP1A2. Drug Metab. Dispos. 1997, 25:1298-1303.
41. Shintu L., Baudoin R., Navratil V., Prot J.-M., Pontoizeau C., Defernez M., Blaise B., Domange C., Péry A., Toulhoat P., Legallais C., Brochot C., Leclerc E., Dumas M.E. Metabolomics-on-a-Chip and Predictive Systems Toxicology in Microfluidic Bioartificial Organs. Anal. chem. 2012, 84:1840-1848.
42. Sivaraman A., Leach J.K., Townsend S., Iida T., Hogan B.J., Stolz D.B., Fry R., Samson L.D., Tannenbaum S.R., Griffith L.G. A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction. Curr. Drug Metab. 2005, 6:569-592.
43. Sjogren E., Lennernas H., Andersson T., Gråsjo J., Bredberg U. The multiple depletion curves method provides accurate estimates of intrinsic clearance (CLint), maximum velocity of the metabolic reaction (Vmax), and michaelis constant (Km): accuracy and robustness evaluated through experimental data and monte carlo simulations. DMD 2009, 37:47-58.
44. Tilles A., Baskaran H., Roy P., Yarmush M., Toner M. Effects of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor. Biotech. Bioeng. 2001, 73:379-389.
45. Viravaidya K., Shuler M.L. Incorporation of 3T3-L1 cells to mimic bioaccumulation in a microscale cell culture analog device for toxicity studies. Biotechnol. Prog. 2004, 20:590-597.
46. Zhang S., Tong W., Zheng B., Susanto T., Xia L., Zhang C., Ananthanarayanan A., Tuo X., Sakban R., Jia R., Iliescu C., Chai K.H., McMillian M., Shen S., Leo H., Yu H. Robust high-throughput sandwich cell-based drug screening platform. Biomaterials 2011, 32:1229-1241.
47. Wang H.X., Ma X.C., Deng Q.L., Li D. Cytotoxicity of flutamide and 2 hydroxyflutamide and their effects on CYP1A2 mRNA in primary rat hepatocytes. Acta Pharmacol. Sin. 2002, 23:562-566.
48. Wang H.X., Liu X., Xu C., Ma X., Long J., Li D. Induction of liver cytochrome P450 1A2 expression by flutamide in rats. Acta Pharmacol. Sinica 2005, 26:1382-1386.