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

by
Montiel-Duarte C, Varela-Rey M, Oses-Prieto J,
Lopez-Zabalza M, Beitia G, Cenarruzabeitia E, Iraburu M.
Department of Biochemistry,
University of Navarra, C/ Irunlarrea 1, 31008,
Navarra, Pamplona, Spain
Biochim Biophys Acta 2002 Oct 9;1588(1):26


ABSTRACT

"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.

History
Club drugs
Abstinence
MDMA/MDE
Liver failure
Brain damage?
Protect and survive
Deaths in New York
Ecstasy and tryptophan
Toxic metabolites of MDMA
Ecstasy and serotonin synthesis
Serotonin/dopamine interactions
Electrophysiological evidence of 5-HT damage
5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine


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