Binge Ethanol and MDMA Combination Exacerbates Toxic Cardiac Effects by Inducing Cellular Stress

• Published in: PloS one Vol. 10; no. 10; p. e0141502
• Main Authors: Navarro-Zaragoza, Javier, Ros-Simó, Clara, Milanés, María-Victoria, Valverde, Olga, Laorden, María-Luisa
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-10-2015; Public Library of Science (PLoS)
• Subjects: Alcohol; Alcohol use; Animals; Antibodies; Binge Drinking; Brain damage; Brain injury; Cardiotoxicity; Cellular stress response; Central nervous system; Chromatography; Consumption; Dosage and administration; Drinking behavior; Drug abuse; Drugs; Ecstasy; Ecstasy (Drug); Ethanol; Ethanol - toxicity; Experiments; Health aspects; Heart; Heart - drug effects; Heart diseases; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heat shock; Heat shock proteins; High performance liquid chromatography; HSP27 Heat-Shock Proteins - metabolism; Hsp27 protein; Hydroxylase; Liquid chromatography; Male; MDMA; MDMA (Droga); Medical research; Mice; Models, Animal; Myocardium - metabolism; N-Methyl-3,4-methylenedioxyamphetamine - toxicity; Noradrenaline; Norepinephrine; Norepinephrine - metabolism; Normetanephrine - metabolism; Oxidative stress; Parameter modification; Pharmacology; Phosphorylation; Rodents; Serine; Stress, Physiological - drug effects; Tyrosine; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; Ventricle; Ventricles (cerebral); Young adults; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141502

Binge drinking is a common pattern of ethanol consumption among young people. Binge drinkers are especially susceptible to brain damage when other substances are co-administered, in particular 3,4 methylendioxymethamphetamine (MDMA). The aim of the present work was to study the mechanisms implicated in the adaptive changes observed after administration of these drugs of abuse. So, we have evaluated the cardiac sympathetic activity and the expression and activation of heat shock protein 27 (HSP27), after voluntary binge ethanol consumption, alone and in combination with MDMA. Both parameters are markers of stressful situations and they could be modified inducing several alterations in different systems. Adolescent mice received MDMA, ethanol or both (ethanol plus MDMA). Drinking in the dark (DID) procedure was used as a model of binge. Noradrenaline (NA) turnover, tyrosine hydroxylase (TH), TH phosphorylated at serine 31 and HSP27 expression and its phosphorylation at serine 82 were evaluated in adolescent mice 48 h, 72 h, and 7 days after treatments in the left ventricle. NA and normetanephrine (NMN) were determined by high-performance liquid chromatography (HPLC); TH and HSP27 expression and phosphorylation were measured by quantitative blot immunollabeling using specific antibodies. Ethanol and MDMA co-administration increased NA turnover and TH expression and phosphorylation versus the consumption of each one of these drugs. In parallel with the described modifications in the cardiac sympathetic activity, our results showed that binge ethanol+MDMA exposure is associated with an increase in HSP27 expression and phosphorylation in the left ventricle, supporting the idea that the combination of both drugs exacerbates the cellular stress induced by ethanol or MDMA alone.