PMID- 30708098 OWN - NLM STAT- MEDLINE DCOM- 20190215 LR - 20190215 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 220 DP - 2019 Mar 1 TI - Binge ethanol and MDMA combination exacerbates HSP27 and Trx-1 (biomarkers of toxic cardiac effects) expression in right ventricle. PG - 50-57 LID - S0024-3205(19)30063-3 [pii] LID - 10.1016/j.lfs.2019.01.050 [doi] AB - 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. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Navarro-Zaragoza, Javier AU - Navarro-Zaragoza J AD - Department of Pharmacology, Faculty of Medicine, University of Murcia, Spain; Instituto Murciano de Investigacion Biosanitaria, Murcia, Spain. Electronic address: jnavarrozaragoza@um.es. FAU - Ros-Simo, Clara AU - Ros-Simo C AD - Grup de Recerca en Neurobiologia del Comportament (GRNC), Universitat Pompeu Fabra, Barcelona, Spain. FAU - Milanes, Maria-Victoria AU - Milanes MV AD - Department of Pharmacology, Faculty of Medicine, University of Murcia, Spain; Instituto Murciano de Investigacion Biosanitaria, Murcia, Spain. FAU - Valverde, Olga AU - Valverde O AD - Grup de Recerca en Neurobiologia del Comportament (GRNC), Universitat Pompeu Fabra, Barcelona, Spain. FAU - Laorden, Maria-Luisa AU - Laorden ML AD - Department of Pharmacology, Faculty of Medicine, University of Murcia, Spain; Instituto Murciano de Investigacion Biosanitaria, Murcia, Spain. LA - eng PT - Journal Article DEP - 20190129 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Biomarkers) RN - 0 (HSP27 Heat-Shock Proteins) RN - 0 (Hspb2 protein, mouse) RN - 0 (Txn1 protein, mouse) RN - 3K9958V90M (Ethanol) RN - 52500-60-4 (Thioredoxins) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Animals MH - Binge Drinking/metabolism MH - Biomarkers/metabolism MH - Body Temperature/drug effects MH - Cardiotoxicity/metabolism MH - Ethanol/adverse effects/metabolism MH - Female MH - Gene Expression Regulation/drug effects MH - HSP27 Heat-Shock Proteins/*drug effects/metabolism MH - Heart/drug effects MH - Heart Ventricles/*drug effects/metabolism MH - Male MH - Mice MH - N-Methyl-3,4-methylenedioxyamphetamine/adverse effects/metabolism MH - Oxidative Stress MH - Phosphorylation MH - Thioredoxins/*drug effects/metabolism OTO - NOTNLM OT - Binge ethanol OT - Heat shock protein 27 OT - MDMA OT - Right ventricle OT - Thioredoxin-1 EDAT- 2019/02/02 06:00 MHDA- 2019/02/16 06:00 CRDT- 2019/02/02 06:00 PHST- 2018/10/17 00:00 [received] PHST- 2019/01/10 00:00 [revised] PHST- 2019/01/28 00:00 [accepted] PHST- 2019/02/02 06:00 [pubmed] PHST- 2019/02/16 06:00 [medline] PHST- 2019/02/02 06:00 [entrez] AID - S0024-3205(19)30063-3 [pii] AID - 10.1016/j.lfs.2019.01.050 [doi] PST - ppublish SO - Life Sci. 2019 Mar 1;220:50-57. doi: 10.1016/j.lfs.2019.01.050. Epub 2019 Jan 29.