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Myocardial expression of TNF-alpha, IL-1beta, IL-6, IL-8, IL-10 and MCP-1 after a single MDMA dose administered in a rat model.

Margherita Neri, Stefania Bello, Alessandro Bonsignore, Fabio Centini, Carmela Fiore, Zeno Földes-Papp, Emanuela Turillazzi, Vittorio Fineschi

Current Pharmaceutical Biotechnology August 2010 DOI: 10.2174/138920110791591517 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics In vivo animal study Peer reviewed
Sample size 25
Population Male rats
Intervention MDMA
Dose 20 mg/kg i.p.
Duration Evaluated at 6, 16 and 24 hours after a single dose
Measures tumor necrosis factor-alpha, IL-1beta, IL-6, IL-8, IL-10, monocyte chemotactic protein-1, Western blot
Topics MDMA
Key points A single 20 mg/kg intraperitoneal dose of MDMA in male rats raised cardiac levels of inflammatory cytokines, with the strongest response at 24 hours for TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, and MCP-1. MDMA and MDA remained detectable in plasma from 6 to 24 hours. The authors interpret the cytokine rise as a possible adaptive response of jeopardized myocardium to MDMA-induced cardiac dysfunction.

Abstract

Indirect effects of 3,4-methylenedioxy-N-methylamphetamine (MDMA) and metabolites on the cardiac cells are well-known, the mechanism(s) underlying direct MDMA-induced cardiotoxicity remaining to be clarified. To better understand the immuno-inflammatory phenomena accompanying the cardiac alterations during MDMA administration, we conducted a study in an in vivo animal model to evaluate the cellular morphological alterations related to the biological response between MDMA administration and inflammatory cytokines (tumor necrosis factor-alpha, IL-1beta, IL-6, 8, 10, and monocyte chemotactic protein-1). A total of 25 male rats were used. The effects were evaluated at 6, 16 and 24 hours after a single dose MDMA administered (20 mg/kg i.p.). We found high levels of the cardioinhibitory cytokines in rat heart after 3 and 6 hs from MDMA administration. Strongest reaction was observed at 24 hs for TNF-alpha, IL-1beta, IL-6, 8, 10 and for MCP-1. Furthermore, we still determined the presence of MDMA and MDA in the plasma of rats treated with MDMA intra-peritoneal single injection; it was present as early at 6 hs and still present 24 hs after treatment. Western blot analysis in cardiac samples demonstrated the IL-1beta and IL-6 reactions in rats died spontaneously at fourth hour. The rise of the selective cardioinhibitory cytokines may be interpreted as the adaptive response of jeopardized myocardium to the cardiac dysfunction resulting from MDMA injection.

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