Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Helena Pontes (Author) Other; Carla Sousa (Author) REIT; Renata Silva (Author) Other; Eduarda Fernandes (Author) FFUP; Helena Carmo (Author) FFUP; Fernando Remiao (Author) FFUP; Felix Carvalho (Author) FFUP; Maria Lourdes Bastos (Author) FFUP

Journal

Title: Toxicology

Vol. 254 No. 1

Pages: 42-50

ISSN: 0300-483X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 27 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-T9K

DOI: 10.1016/j.tox.2008.09.009

Abstract (EN): 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 24 h, 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9