Neurotoxicity of beta-Keto Amphetamines: Deathly Mechanisms Elicited by Methylone and MDPV in Human Dopaminergic SH-SY5Y Cells

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Valente, MJ (Autor) Outra; Maria de Lourdes Bastos (Autor) FFUP; Eduarda Fernandes (Autor) FFUP; Felix Carvalho (Autor) FFUP; de Pinho, PG (Autor) FFUP; Carvalho, M (Autor) Outra

Revista

Título: Acs Chemical Neuroscience

Vol. 8

Páginas: 850-859

ISSN: 1948-7193

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 53 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-00M-Q70

DOI: 10.1021/acschemneuro.6b00421

Abstract (EN): Synthetic cathinones (beta-keto amphetamines) act as potent CNS stimulants similarly to classical amphetamines, which raise concerns about their potential neurotoxic effects. The present in vitro study aimed to explore and compare the mechanisms underlying the neurotoxicity of two commonly abused cathinone derivatives, 3,4-methylenedioxymetlicathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), with those of 3,4-methylenedioxymethamphetamine (MDMA), using undifferentiated and differentiated SH-SYSY cells. Following a 24 h exposure period, methylone and MDPV induced loss of cell viability in a concentration-dependent manner, in the following order of potency: MDPV approximate to MDMA > methylone. Dopaminergic differentiated cells evidenced higher sensitivity to the neurotoxic effects of both cathinones and MDMA than the undifferentiated ones, but this effect was not inhibited by the DAT inhibitor GBR 12909. Intracellular oxidative stress mediated by methylone and MDPV was demonstrated by the increase in reactive oxygen and nitrogen species (ROS and RNS) production, depletion of intracellular reduced glutathione and increased oxidized glutathione levels. All three drugs elicited mitochondrial impairment, characterized by the mitochondrial membrane potential (Delta psi m) dissipation and intracellular ATP depletion. Apoptosis was found to be a common mechanism of cell death induced by methylone and MDPV, with evident chromatin condensation and formation of pyknotic nuclei, and activation of caspases 3, 8, and 9. In conclusion, the present data shows that oxidative stress and mitochondria] dysfunction play a role in cathinones-induced neuronal damage, ultimately leading to cell death by apoptosis.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10