Binge ethanol and MDMA combination exacerbates HSP27 and Trx-1 (biomarkers of toxic cardiac effects) expression in right ventricle

Aims: Oxidative stress caused by exposure to drugs of abuse such as ethanol or 3, 4 methylenedioxymethamphetamine (MDMA) may derive from direct or indirect effects in many organs including the heart. The aim of the present work was to evaluate cardiac sympathetic activity and the expression and activation of two antioxidant proteins: heat shock protein27 (HSP27) and thioredoxin-1 (Trx-1) after voluntary binge ethanol consumption, alone and in combination with MDMA. Material and methods: Adolescent mice received MDMA, ethanol or both. Drinking in the dark (DID) procedure was used as a model of binge. HSP27 expression and phosphorylation at serine 82 (pHSP27), Trx-1 expression, tyrosine hydroxylase (TH) and TH phosphorylated at serine 31 (pTH) were evaluated in adolescent mice 48 h and 7 days after treatments in the right ventricle. TH, HSP27 expression and phosphorylation and Trx-1 expression were measured by quantitative blot immunolabeling using specific antibodies. Key findings: The expression of HSP27, pHSP27, Trx-1, total TH and pTH in the right ventricle was increased after binge ethanol or MDMA alone. In addition, the combination of binge ethanol + MDMA enhanced TH expression and phosphorylation versus their individual administration. Significance: These results indicate that this combination could produce higher activation of sympathetic pathways, which could trigger an increased cell stress. On the other hand, increased HSP27, pHSP27 and Trx-1 expression in the right ventricle by ethanol + MDMA could be a protective mechanism to reduce the adverse effects of oxidative stress caused by both drugs of abuse. The funders of this research have been the Spanish Ministry of Economy and Innovation and FEDER (SAF/FEDER 2013-49076-P, SAF2017-85679-R and SAF2013-41761-R), the Spanish Ministry of Health, Social Affairs and Equality (PNSD 2014-020) and Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Salud -ISCIII-FEDER- RETIC-Trastornos Adictivos RTA, RD12/0028/0003 and RD12/0028/0024).