Oxidative Stress in Rat Retina and Hippocampus after Chronic MDMA (‘ecstasy’) Administration

Neurochemical Research - Tập 32 - Trang 1156-1162 - 2007
María Miranda1,2, Francisco Bosch-Morell1,2, Siv Johnsen-Soriano1,2, Jorge Barcia1, Inmaculada Almansa1, Samuel Asensio1, Javier Araiz3, Angel Messeguer4, Francisco J. Romero1,2
1Instituto CEU sobre Drogas y Conductas Adictivas (IDYCA), Universidad CEU Cardenal Herrera, Moncada, Valencia, Spain
2Fundación Oftalmológica del Mediterráneo, Valencia, Spain
3Departamento de Oftalmología, Universidad del País Vasco, Lejona, Spain
4Department of Biological Organic Chemistry, Institut d’Investigacions Quimiques i Ambientals de Barcelona (CSIC), Barcelona, Spain

Tóm tắt

The effects of MDMA administration on oxidative stress markers in rat eye and hippocampus, and the neuroprotective effects of the antioxidant 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6) have been studied. MDMA effects on liver were used for comparison with those in eye and hippocampus and to test CR-6 protective effects. Another goal was to test for apoptosis in retinal cells, as it is known that happens in liver and brain. After 1 week of ecstasy administration, malondialdehyde (MDA) concentration increased, glutathione peroxidase (GPx) activity and glutathione (GSH) content decreased in liver, as previously described. MDA concentration increased and GPx activity decreased in hippocampus; whereas no change was observed in GSH concentration. MDMA decreased ocular GSH concentration and GPx activity; no change was observed in MDA concentration. The number of TUNEL-positive nuclei increased significantly in rat retinas after 1 week of MDMA administration. CR-6 normalized the modifications in liver, hippocampus and retina mentioned above.

Tài liệu tham khảo

Saunders N (1995) In: Ecstasy and the dance culture. Nicholas Saunders, London Robbins TW, Everitt BJ (1999) Drug addiction: bad habits add up. Nature 398:567–570 Reneman L (2003) Designer drugs: how dangerous are they? J Neural Transm 66:61–83 Schmidt CJ (1987) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. J Pharmacol Exp Ther 240:1–7 Battaglia SY, De Souza EB (1988) MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain serotonin neurons. Pharmacol Biochem Behav 29:269–274 Kalant H (2001) The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. CMAJ 165:7 Beitia G, Cobreros A, Sainz L et al (2000) Ecstasy-induced toxicity in rat liver. Liver 20:8–15 Gudelsky GA, Yamamoto BK (2003) Neuropharmacology and neurotoxicity of 3,4-methylenedioxymethamphetamine. Methods Mol Med 79:55–73 Zhou JF, Zhou YH, Zhang L et al (2003) 3,4-methylenedioxymethamphetamine (MDMA) abuse markedly inhibits acetylcholinesterase activity and induces severe oxidative damage and liperoxidative damage. Biomed Environ Sci 16:53–61 Cadet JL, Thiriet N, Jayanthi S (2001) Involvement of free radicals in MDMA-induced neurotoxicity in mice. Ann Med Interne 152:57–59 Colado MI, O´Shea E, Granados R et al (1997) In vivo evidence for free radical involvement in 5-HT following administration of MDMA (“ecstasy”) and p-chloroamphetamine but not the degeneration following fenfluramine. Br J Pharmacol 121:889–900 Gudelsky GA (1996) Effect of ascorbate and cysteine on the 3,4-methyl-enedioxymethamphetamine-induced depletion of brain serotonin. J Neural Transm 102:1397–1404 Shankaran M, Yamamoto BK, Gudelski GA (2001) Ascorbic acid prevents 3,4-methylenedioxymethamphetamine (MDMA)-induced hydroxyl radical formation and the behavioral and neurochemical consequences of the depletion of the brain. Synapse 40:55–64 Aguirre N, Barrionuevo M, Ramírez MJ et al (1999). Alpha-lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity. Neuroreport 10:3675–3680 Clauwaert KM, Van Bocxlaer JF, De Letter EA et al (2000) Determination of the designer drugs 3, 4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, and 3,4-methylenedioxyamphetamine with HPLC and fluorescence detection in whole blood, serum, vitreous humor, and urine. Clin Chem 46:1968–1977 Irurre J, Casas J, Ramos I et al (1993) Inhibition of rat liver microsomal lipid peroxidation elicited by 2,2-dimethylchromenes and chromans containing fluorinated moieties resistant to cytochrome P-450 metabolism. Bioorg Med Chem 1:219–225 Montoliu C, Llansola M, Sáez R et al (1999) Prevention of glutamate neurotoxicity in cultured neuronas by 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6), a sacvenger of nitric oxide. Biochem Pharmacol 58:255–261 Jimenez A, Jorda EG, Verdaguer E et al (2004) Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells. Toxicol Appl Pharmacol 196:223–234 Montiel-Duarte C, Ansorena E, Lopez-Zabalza MJ et al (2004) Role of reactive oxygen species, glutathione and NF-kappaB in apoptosis induced by 3,4-methylenedioxymethamphetamine (“Ecstasy”) on hepatic stellate cells. Biochem Pharmacol 67:1025–1033 Simantov R, Tauber M (1997) The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells. FASEB J 11:141–146 Casas J, Gorchs G, Sanchez-Baeza F et al (1992) Inhibition of rat liver microsomal lipid peroxidation elicited by simple 2,2-dimethylchromenes and chromans structurally related to precocenes. J Agric Food Chem 40:585–590 Richard MJ, Guiraud P, Meo J et al (1992) High performance liquid chromatography separation of malondialdehyde thiobarbituric acid adduct in biological materials (plasma and human cell) using a comercially available reagent. J Chromatogr 577:9–18 Romero MJ, Bosch-Morell F, Romero B et al (1998) Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients. Free Radical Biol Med 25:993–997 Lawrence RA, Parkhill LK, Burk RF (1978) Hepatic cytosolic non-selenium dependent glutathione peroxidase activity: its nature and the effect of selenium deficiency. J Nutr 108:981–987 Reed DJ, Babson JR, Beatty PW et al (1980) High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides. Anal Biochem 106:55–62 Lowry OH, Rosebrough NJ, Farr AL et al (1951). Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275 Doly M, Droy-Lefaix MT, Braquet P (1992) Oxidative stress in diabetic retina. EXS62:299–307 Carvalho M, Milhazes N, Remiao F et al (2004) Hepatotoxicity of 3,4-methylenedioxyamphetamine and alpha-methyldopamine in isolated rat hepatocytes: formation of glutathione conjugates. Arch Toxicol 78:16–24 Colado MI, Camarero J, Mecham AO et al (2001) A study of the mechanisms involved in the neurotoxic action of 3,4-methylendioxymethamphetamine (MDMA, “ecstasy”) on dopamine neurones in mouse brains. Br J Pharmacol 134:1711–1723 Jayanthi S, Ladenheim B, Andrews AM et al (1999) Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphethamine (Ecstasy). Neuroscience 91:1379–1387 Camarero J, Sanchez V, O’Shea E et al (2002) Studies, using in vivo microdialysis, on the effect of the dopamine uptake inhibitor GBR 12909 on 3,4-methylenedioxymethamphetamine (‘ecstasy’)-induced dopamine release and free radical formation in the mouse striatum. J Neurochem 81:961–972 Gastinger MJ, Singh RS, Barber AJ (2006) Loss of Cholinergic and Dopaminergic Amacrine Cells in Streptozotocin-Diabetic Rat and Ins2Akita-Diabetic Mouse Retinas. Invest Ophthalmol Vis Sci 47:3143–3150 Takita H, Yoneya S, Gehlbach PL et al (2003) Retinal neuroprotection against ischemic injury mediated by intraocular gene transfer of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci 44:4497–4504 Jacobsen LK, Mencl WE, Pugh KR et al (2004) Preliminary evidence of hippocampal dysfunction in adolescent MDMA (“ecstasy”) users: possible relationship to neurotoxic effects. Psychopharmacology 173:383–390 Huether G, Zhou D, Ruther E (1997) Causes and consequences of the loss of serotonergic presynapses elicited by the consumption of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) and its congeners. J Neural Transm 104:771–794 Parrott AC (2001) Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research. Hum Psychopharmacol 16:557–577 Sanvicens N, Gómez-Vicente V, Masip I et al (2004) Oxidative stress-induced apoptosis in retinal photoreceptor cells is mediated by calpains and caspases and blocked by the oxygen radical scavenger CR-6. J Biol Chem 279:39268–39278