Ecstasy-induced toxicity in SH-SY5Y differentiated cells: Role of hyperthermia and metabolites

Archives of Toxicology

Volumn 88, Issue 2, 2014, Pages 515-531

  Barbosa, Daniel José ^a   Capela, João Paulo ^a,b   Silva, Renata ^a   Ferreira, Luísa Maria ^c   Branco, Paula Sério ^c   Fernandes, Eduarda ^a   Bastos, Maria Lourdes ^a   Carvalho, Félix ^a  

^a UNIVERSITY OF PORTO   (Portugal)

^b UNIVERSIDADE FERNANDO PESSOA   (Portugal)

^c UNIVERSIDADE NOVA DE LISBOA   (Portugal)

Author keywords

3,4 Methylenedioxymethamphetamine (MDMA; "ecstasy"); Hyperthermia; MDMA metabolites; Neurotoxicity; SH SY5Y differentiated cells

Indexed keywords

N-METHYL-3,4-METHYLENEDIOXYAMPHETAMINE; 3,4-METHYLENEDIOXYAMPHETAMINE; ACETYLCYSTEINE; CASPASE 3; CELL DEATH; CELL DIFFERENTIATION; CELL LINE; DEOXYEPINEPHRINE; FEVER; GLUTATHIONE; HUMANS; MITOCHONDRIA; NEURONS; NEUROTOXICITY SYNDROMES; TEMPERATURE;

EID: 84893906917     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-013-1147-9     Document Type: Article

References (62)

1. Ádori C, Andó RD, Kovács GG, Bagdy G (2006) Damage of serotonergic axons and immunolocalization of Hsp27, Hsp72, and Hsp90 molecular chaperones after a single dose of MDMA administration in Dark Agouti rat: temporal, spatial, and cellular patterns. J Comp Neurol 497:251-269
2. Aguirre P, Valdés P, Aracena-Parks P, Tapia V, Núñez MT (2007) Upregulation of γ-glutamate-cysteine ligase as part of the long-term adaptation process to iron accumulation in neuronal SH-SY5Y cells. Am J Physiol Cell Physiol 292:2197-2203
3. Bai F, Lau SS, Monks TJ (1999) Glutathione and N-acetylcysteine conjugates of α-methyldopamine produce serotonergic neurotoxicity: possible role in methylenedioxyamphetamine-mediated neurotoxicity. Chem Res Toxicol 12:1150-1157
4. Bai F, Jones DC, Lau SS, Monks TJ (2001) Serotonergic neurotoxicity of 3,4-(±)-methylenedioxyamphetamine and 3,4-(±)- methylendioxymethamphetamine (ecstasy) is potentiated by inhibition of γ-glutamyl transpeptidase. Chem Res Toxicol 14:863-870
5. Ballatori N, Krance SM, Marchan R, Hammond CL (2009) Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology. Mol Aspects Med 30:13-28
6. Barbosa DJ, Capela JP, Oliveira JMA et al (2012) Pro-oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes. Br J Pharmacol 165:1017-1033
7. Barbosa DJ, Capela JP, Silva R et al (2013) The mixture of "ecstasy" and its metabolites is toxic to human SH-SY5Y differentiated cells at in vivo relevant concentrations. Arch Toxicol. doi: 10.1007/s00204-013-1120-7
8. Beitia G, Cobreros A, Sainz L, Cenarruzabeitia E (1999) 3,4-Methylenedioxymethamphetamine (ecstasy)-induced hepatotoxicity: effect on cytosolic calcium signals in isolated hepatocytes. Liver 19:234-241
9. Capela JP, Meisel A, Abreu AR et al (2006a) Neurotoxicity of ecstasy metabolites in rat cortical neurons, and influence of hyperthermia. J Pharmacol Exp Ther 316:53-61
10. Capela JP, Ruscher K, Lautenschlager M et al (2006b) Ecstasy-induced cell death in cortical neuronal cultures is serotonin 2A-receptor-dependent and potentiated under hyperthermia. Neuroscience 139:1069-1081
11. Capela JP, Macedo C, Branco PS et al (2007) Neurotoxicity mechanisms of thioether ecstasy metabolites. Neuroscience 146:1743-1757
12. Capela JP, Carmo H, Remião F, Bastos ML, Meisel A, Carvalho F (2009) Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol 39:210-271
13. Carvalho M, Carvalho F, Bastos ML (2001) Is hyperthermia the triggering factor for hepatotoxicity induced by 3,4-methylenedioxymethamphetamine (ecstasy)? An in vitro study using freshly isolated mouse hepatocytes. Arch Toxicol 74:789-793
14. Carvalho M, Hawksworth G, Milhazes N et al (2002) Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells. Arch Toxicol 76:581-588
15. Carvalho M, Remiao F, Milhazes N et al (2004a) The toxicity of N-methyl-alpha-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine. Toxicology 200:193-203
16. Carvalho M, Remião F, Milhazes N et al (2004b) Metabolism is required for the expression of ecstasy-induced cardiotoxicity in vitro. Chem Res Toxicol 17:623-632
17. Carvalho M, Carmo H, Costa VM et al (2012) Toxicity of amphetamines: an update. Arch Toxicol 86:1167-1231
18. Chadwick IS, Curry PD, Linsley A, Freemont AJ, Doran B (2001) Ecstasy, 3-4 methylenedioxymethamphetamine (MDMA), a fatality associated with coagulopathy and hyperthermia. J R Soc Med 84:371
19. Chu T, Kumagai Y, DiStefano EW, Cho AK (1996) Disposition of methylenedioxymethamphetamine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depletion. Biochem Pharmacol 51:789-796
20. Commins DL, Vosmer G, Virus RM, Woolverton WL, Schuster CR, Seiden LS (1987) Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. J Pharmacol Exp Ther 241:338-345
21. Constantinescu R, Constantinescu AT, Reichmann H, Janetzky B (2007) Neuronal differentiation and long-term culture of the human neuroblastoma line SH-SY5Y. J Neural Transm (Suppl 72):17-28
22. de la Torre R, Farré M (2004) Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans. Trends Pharmacol Sci 25:505-508
23. Docherty JR, Green AR (2010) The role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives. Br J Pharmacol 160:1029-1044
24. Erives GV, Lau SS, Monks TJ (2008) Accumulation of neurotoxic thioether metabolites of 3,4-(±)-methylenedioxymethamphetamine in rat brain. J Pharmacol Exp Ther 324:284-291
25. Erritzoe D, Frokjaer VG, Holst KK et al (2011) In vivo imaging of cerebral serotonin transporter and serotonin2a receptor binding in 3,4-methylenedioxymethamphetamine (mdma or "ecstasy") and hallucinogen users. Arch Gen Psychiatry 68:562-576
26. Escobedo I, O'Shea E, Orio L et al (2005) A comparative study on the acute and long-term effects of MDMA and 3,4-dihydroxymethamphetamine (HHMA) on brain monoamine levels after i.p. or striatal administration in mice. Br J Pharmacol 144:231-241
27. Esteban B, O'Shea E, Camarero J, Sanchez V, Green AR, Colado MI (2001) 3,4-Methylenedioxymethamphetamine induces monoamine release, but not toxicity, when administered centrally at a concentration occurring following a peripherally injected neurotoxic dose. Psychopharmacology 154:251-260
28. Farfel GM, Seiden LS (1995) Role of hypothermia in the mechanism of protection against serotonergic toxicity. I. Experiments using 3,4-methylenedioxymethamphetamine, dizocilpine, CGS 19755 and NBQX. J Pharmacol Exp Ther 272:860-867
29. Felim A, Herrera G, Neudörffer A, Blanco M, O'Connor J, Largeron M (2009) Synthesis and in vitro cytotoxicity profile of the R-enantiomer of 3,4-dihydroxymethamphetamine (R-(-)-HHMA): comparison with related catecholamines. Chem Res Toxicol 23:211-219
30. Ferreira PS, Nogueira TB, Costa VM et al (2013) Neurotoxicity of "ecstasy" and its metabolites in human dopaminergic differentiated SH-SY5Y cells. Toxicol Lett 216:159-170
31. Godwin AK, Meister A, O'Dwyer PJ, Huang CS, Hamilton TC, Anderson ME (1992) High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis. Proc Natl Acad Sci USA 89:3070-3074
32. Gollamudi R, Ali SF, Lipe G et al (1989) Influence of inducers and inhibitors on the metabolism in vitro and neurochemical effects in vivo of MDMA. Neurotoxicology 10:455-466
33. Granado N, Ares-Santos S, Oliva I et al (2011) Dopamine D2-receptor knockout mice are protected against dopaminergic neurotoxicity induced by methamphetamine or MDMA. Neurobiol Dis 42:391-403
34. Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacol Rev 55:463-508
35. Hatzidimitriou G, McCann UD, Ricaurte GA (1999) Altered serotonin innervation patterns in the forebrain of monkeys treated with (±)3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery. J Neurosci 19:5096-5107
36. Henry JA, Jeffreys KJ, Dawling S (1992) Toxicity and deaths from 3,4-methylenedioxymethamphetamine ("ecstasy"). Lancet 340:384-387
37. Hiramatsu M, Kumagai Y, Unger SE, Cho AK (1990) Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. J Pharmacol Exp Ther 254:521-527
38. Johnson BN, Yamamoto BK (2010) Chronic stress enhances the corticosterone response and neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the role of ambient temperature. J Pharmacol Exp Ther 335:180-189
39. Jones DC, Duvauchelle C, Ikegami A et al (2005) Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther 313:422-431
40. Kish SJ, Fitzmaurice PS, Chang LJ, Furukawa Y, Tong J (2010a) Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study. J Psychopharmacol 24:281-284
41. Kish SJ, Lerch J, Furukawa Y et al (2010b) Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study. Brain 133:1779-1797
42. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265-275
43. Macedo C, Branco PS, Ferreira LM et al (2007) Synthesis and cyclic voltammetry studies of 3,4-methylenedioxymethamphetamine (MDMA) human metabolites. J Health Sci 53:31-42
44. Malberg JE, Seiden LS (1998) Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. J Neurosci 18:5086-5094
45. McCann UD, Ridenour A, Shaham Y, Ricaurte GA (1994) Serotonin neurotoxicity after (±)3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy"): a controlled study in humans. Neuropsychopharmacology 10:129-138
46. Miller RT, Lau SS, Monks TJ (1996) Effects of intracerebroventricular administration of 5-(glutathion-S-yl)-α-methyldopamine on brain dopamine, serotonin, and norepinephrine concentrations in male Sprague-Dawley rats. Chem Res Toxicol 9:457-465
47. Monks TJ, Jones DC, Fengju B, Lau SS (2004) The role of metabolism in 3,4-Methylenodioxyamphetamine and 3,4-Methylenodioxymethamphetamine (Ecstasy) toxicity. Ther Drug Monit 26:132-136
48. Núñez MT, Gallardo V, Muñoz P et al (2004) Progressive iron accumulation induces a biphasic change in the glutathione content of neuroblastoma cells. Free Radic Biol Med 37:953-960
49. Parrott AC (2012) MDMA and 5-HT neurotoxicity: the empirical evidence for its adverse effects in humans - no need for translation. Br J Pharmacol 166:1518-1520
50. Patel NJ, Fullone JS, Anders MW (1993) Brain uptake of S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine, the glutathione and cysteine S-conjugates of the neurotoxin dichloroacetylene. Brain Res Mol Brain Res 17:53-58
51. Presgraves S, Ahmed T, Borwege S, Joyce J (2003) Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. Neurotox Res 5:579-598
52. Quednow BB, Jessen F, Kühn K, Maier W, Daum I, Wagner M (2006) Memory deficits in abstinent MDMA (ecstasy) users: neuropsychological evidence of frontal dysfunction. J Psychopharmacol 20:373-384
53. Ricaurte GA, DeLanney LE, Irwin I, Langston JW (1988) Toxic effects of MDMA on central serotonergic neurons in the primate: importance of route and frequency of drug administration. Brain Res 446:165-168
54. Roberts GMP, Nestor L, Garavan H (2009) Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task. Brain Res 1292:71-81
55. Schmued LC (2003) Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA. Brain Res 974:127-133
56. Shenouda SK, Varner KJ, Carvalho F, Lucchesi PA (2009) Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Cardiovasc Toxicol 9:30-38
57. Shi MM, Kugelman A, Iwamoto T, Tian L, Forman HJ (1994) Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells. J Biol Chem 269:26512-26517
58. Silva R, Boldt S, Costa VM et al (2007) Evaluation of GSH adducts of adrenaline in biological samples. Biomed Chromatogr 21:670-679
59. Slot AJ, Wise DD, Deeley RG, Monks TJ, Cole SPC (2008) Modulation of human multidrug resistance protein (MRP) 1 (ABCC1) and MRP2 (ABCC2) transport activities by endogenous and exogenous glutathione-conjugated catechol metabolites. Drug Metab Dispos 36:552-560
60. Tai YF, Hoshi R, Brignell CM et al (2011) Persistent nigrostriatal dopaminergic abnormalities in ex-users of MDMA ("Ecstasy"): an 18F-dopa PET study. Neuropsychopharmacology 36:735-743
61. Takeuchi H, Yanagida T, Inden M et al (2009) Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models. J Neurosci Res 87:576-585
62. Touriño C, Zimmer A, Valverde O (2010) THC prevents MDMA neurotoxicity in mice. PLoS ONE 5:e9143