Chronic exposure to ethanol exacerbates MDMA-induced hyperthermia and exposes liver to severe MDMA-induced toxicity in CD1 mice

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

Authors

Pontes H (Author) Other; Duarte JA (Author) FADEUP; de Pinho, PG (Author) Other; Soares ME (Author) Other; Fernandes E (Author) FFUP; Dinis-Oliveira RJ (Author) FMUP; Sousa C (Author) REIT; Silva R (Author) Other; Carmo H (Author) FFUP; Casal S (Author) FFUP; Remião F (Author) FFUP; Carvalho F (Author) FFUP; Bastos ML (Author) FFUP

Journal

Title: Toxicology

Vol. 252

Pages: 64-71

ISSN: 0300-483X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 39 Citations

Scopus - 40 Citations

Pubmed / Medline

Scientific classification

CORDIS: Health sciences > Pharmacological sciences > Toicology

Other information

Authenticus ID: P-003-VEM

DOI: 10.1016/j.tox.2008.07.064

Abstract (EN): 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative drug with entactogenic, empathogenic and hallucinogenic properties, commonly consumed at rave parties in a polydrug abuse pattern, especially with cannabis, tobacco and ethanol. Since both MDMA and ethanol may cause deleterious effects to the liver, the evaluation of their putative hepatotoxic interaction is of great interest, especially considering that most of the MDMA users are regular ethanol consumers. Thus, the aim of the present study was to evaluate, in vivo, the acute hepatotoxic effects of MDMA (10mg/kg i.p.) in CD-1 mice previously exposed to 12% ethanol as drinking fluid (for 8 weeks). Body temperature was continuously measured for 12 h after MDMA administration and, after 24 h, hepatic damage was evaluated. The administration of MDMA to non pre-treated mice resulted in sustained hyperthermia, which was significantly increased in ethanol pre-exposed mice. A correspondent higher increase of hepatic heat shock transcription factor (HSF-1) activation was also observed in the latter group. Furthermore, MDMA administration resulted in liver damage as confirmed by histological analysis, slight decrease in liver weight and increased plasma transaminases levels. These hepatotoxic effects were also exacerbated when mice were pre-treated with ethanol. The activities of some antioxidant enzymes (such as SOD, GPx and Catalase) were modified by ethanol, MDMA and their joint action. The hepatotoxicity resulting from the simultaneous exposure to MDMA and ethanol was associated with a higher activation of NF-kappa B, indicating a pro-inflammatory effect in this organ. In conclusion, the obtained results strongly suggest that the consumption of ethanol increases the hyperthermic and hepatotoxic effects associated with MDMA abuse.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8