Induction of glutathione synthesis and conjugation by 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dihydroxymethamphetamine (HHMA) in human and rat liver cells, including the protective role of some antioxidants

Highlights ► The MDMA metabolite (HHMA) causes hepatotoxicity by interaction with the GSH system. ► N-acetyl-cysteine could counteract MDMA-induced cytotoxicity and restore GSH levels. ► MDMA-mediated detoxification could be stimulated by NAC supplementation. ► Sulforaphane (SFN) increased MDMA-indu...

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Veröffentlicht in:	Toxicology (Amsterdam) 2011-11, Vol.289 (2), p.175-184
Hauptverfasser:	Antolino-Lobo, Irene, Meulenbelt, Jan, Molendijk, Jeffrey, Nijmeijer, Sandra M, Scherpenisse, Peter, van den Berg, Martin, van Duursen, Majorie B.M
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetylcysteine Animals Antioxidant antioxidants Antioxidants - metabolism Antioxidants - pharmacology Biological and medical sciences Cell Survival - drug effects Cell Survival - physiology cell viability Cells, Cultured cysteine cytotoxicity Deoxyepinephrine - analogs & derivatives Deoxyepinephrine - metabolism Deoxyepinephrine - toxicity drug interactions Drug Interactions - physiology Emergency epithelial cells gene expression glutamic acid glutathione Glutathione - biosynthesis Glutathione - metabolism glutathione transferase GSH GST hepatocytes Hepatocytes - drug effects Hepatocytes - metabolism hepatotoxicity Humans liver Male MDMA Medical sciences metabolism metabolites N-Methyl-3,4-methylenedioxyamphetamine - metabolism N-Methyl-3,4-methylenedioxyamphetamine - toxicity poisoning Protective Agents - metabolism Protective Agents - pharmacology protective effect protein subunits PXR Rats Rats, Wistar Toxicology γGCL
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Zusammenfassung:	Highlights ► The MDMA metabolite (HHMA) causes hepatotoxicity by interaction with the GSH system. ► N-acetyl-cysteine could counteract MDMA-induced cytotoxicity and restore GSH levels. ► MDMA-mediated detoxification could be stimulated by NAC supplementation. ► Sulforaphane (SFN) increased MDMA-induced cytotoxicity and GSH depletion in vitro . ► SFN use should be considered with care because of risk for drug–drug interactions.
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2011.08.012