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Diana Dias da Silva, Elisabete Silva, Félix Carvalho and Helena Carmo Mixtures of 3,4-methylenedioxymethamphetamine (ecstasy) and its major human metabolites act additively to induce significant toxicity to liver cells when combined at low, non-cytotoxic concentrations Journal of Applied Toxicology 34

Article first published online: 14 MAY 2013 | DOI: 10.1002/jat.2885

Combination effects between methylenedioxymethamphetamine (MDMA; ecstasy) and its metabolites methylenedioxyamphetamine, α-methyldopamine and N-methyl-α-methyldopamine were evaluated in Hep G2 cells at normal (37 ºC) and hyperthermic (40.5  ºC) incubation conditions. Joint cytotoxic effects measured as viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay were predicted using the concentration addition and independent action models. The combination of MDMA and its metabolites induced additive toxicity that was accurately predicted by the concentration addition model. Substantial combination effects were noted for mixtures at individually non-cytotoxic concentrations. Hyperthermic incubations dramatically increased individual and joint cytotoxicity.

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