3,4-Methylenedioxymethamphetamine ("Ecstasy") induces apoptosis of cultured rat liver cells

"Ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) has been shown to be hepatotoxic for human users, but molecular mechanisms involved in this effect remained poorly understood. MDMA-induced cell damage is related to programmed cell death in serotonergic and dopaminergic neurons. However,...

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Detalles Bibliográficos
Autores: Montiel-Duarte, Cristina, Varela Rey, Marta María, Osés-Prieto, Juan A, López-Zabalza, María Jesús, Beitia, Guadalupe, Cenarruzabeitia, Edurne, Iraburu, María J
Tipo de recurso: artículo
Fecha de publicación:2002
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/39366
Acceso en línea:https://hdl.handle.net/10347/39366
Access Level:acceso abierto
Palabra clave:MDMA
Hepatic stellate cell
Hepatocyte
bcl-2 family protein
Cytochrome c
Caspase 3
Investigación
Descripción
Sumario:"Ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) has been shown to be hepatotoxic for human users, but molecular mechanisms involved in this effect remained poorly understood. MDMA-induced cell damage is related to programmed cell death in serotonergic and dopaminergic neurons. However, until now there has been no evidence of apoptosis induced by MDMA in liver cells. Here we demonstrate that exposure to MDMA caused apoptosis of freshly isolated rat hepatocytes and of a cell line of hepatic stellate cells (HSC), as shown by chromatin condensation of the nuclei and accumulation of oligonucleosomal fragments in the cytoplasm. In both cell types, apoptosis correlated with decreased levels of bcl-x(L), release of cytochrome c from the mitochondria and activation of caspase 3. In HSC, but not in hepatocytes, MDMA induced poly(ADP-ribose)polymerase (PARP) proteolysis. These results suggest that apoptosis of liver cells could be involved in the hepatotoxicity of MDMA.