Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes.
Helena Pontes, Carla Sousa, Renata Silva, Eduarda Fernandes, Helena Carmo, Fernando Remião, Félix Carvalho, Maria Lourdes Bastos
Toxicology December 5, 2008 DOI: 10.1016/j.tox.2008.09.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Primary cultured rat hepatocytes |
| Interventions | Ethanol MDMA |
| Duration | 24 hours |
| Topics | MDMA |
| Key points | Co-incubation of primary cultured rat hepatocytes with ethanol and MDMA for 24 hours produced synergistic hepatotoxicity, with high cell death ratios, disturbed cellular redox status, and decreased energy levels, occurring preferentially through necrosis. These effects were dramatically aggravated under hyperthermic conditions (40.5 degrees C) compared with normothermia (36.5 degrees C). |
Abstract
Ethanol is frequently consumed along with 3,4-methylenedioxymethamphetamine (MDMA; ecstasy). Since both compounds are hepatotoxic and are metabolized in the liver, an increased deleterious interaction resulting from the concomitant use of these two drugs seems plausible. Another important feature of MDMA-induced toxicity is hyperthermia, an effect known to be potentiated after continuous exposure to ethanol. Considering the potential deleterious interaction, the aim of the present study was to evaluate the hepatotoxic effects of ethanol and MDMA mixtures to primary cultured rat hepatocytes and to elucidate the mechanism(s) underlying this interaction. For this purpose, the toxicity induced by MDMA to primary cultured rat hepatocytes in absence or in presence of ethanol was evaluated, under normothermic (36.5 degrees C) and hyperthermic (40.5 degrees C) conditions. While MDMA and ethanol, by themselves, had discrete effects on the analysed parameters, which were slightly aggravated under hyperthermia, the simultaneous incubation of MDMA and ethanol for 24h, resulted in high cell death ratios accompanied by a significant disturbance of cellular redox status and decreased energy levels. Evaluation of apoptotic/necrotic features provided clear evidences that the cell death occurs preferentially through a necrotic pathway. All the evaluated parameters were dramatically aggravated when cells were incubated under hyperthermia. In conclusion, co-exposure of hepatocytes to ethanol and MDMA definitely results in a synergism of the hepatotoxic effects, through a disruption of the cellular redox status and enhanced cell death by a necrotic pathway in a temperature-dependent extent.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 7
- Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage Current Pharmaceutical Biotechnology June 27, 2010
- Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats International Journal of Molecular Sciences March 12, 2019
- Pills and pints: Risky drinking and alcohol‐related harms among regular ecstasy users in Australia Drug and Alcohol Review September 15, 2011
- GC-MS metabolomics reveals disturbed metabolic pathways in primary mouse hepatocytes exposed to subtoxic levels of 3,4-methylenedioxymethamphetamine (MDMA). Archives of Toxicology November 2018
- Neurotoxicity of "ecstasy" and its metabolites in human dopaminergic differentiated SH-SY5Y cells. Toxicology Letters February 4, 2013
and 2 more in the library
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and 12 more in the library