Ethanol addictively enhances the in vitro cardiotoxicity of cocaine through oxidative damage, energetic deregulation, and apoptosis

Archives of Toxicology
Maria João MartinsDiana Dias da Silva

Abstract

Cocaine (COC) is frequently consumed in polydrug abuse settings, and ethanol (EtOH) is the most prominent co-abused substance. Clinical data and experimental evidence suggest that the co-administration of COC with EtOH can be more cardiotoxic than EtOH or COC alone, but information on the molecular pathways involved is scarce. Since these data are crucial to potentiate the identification of therapeutic targets to treat intoxications, we sought to (i) elucidate the type of interaction that occurs between both substances, and (ii) assess the mechanisms implicated in the cardiotoxic effects elicited by COC combined with EtOH. For this purpose, H9c2 cardiomyocytes were exposed to COC (104 µM-6.5 mM) and EtOH (977 µM-4 M), individually or combined at a molar ratio based on blood concentrations of intoxicated abusers (COC 1: EtOH 9; 206 µM-110 mM). After 24 h, cell metabolic viability was recorded by the MTT assay and mixture toxicity expectations were calculated using the independent action (IA) and concentration addition (CA) models. EtOH (EC50 305.26 mM) proved to act additively with COC (EC50 2.60 mM) to significantly increase the drug in vitro cardiotoxicity, even when both substances were combined at individually non-cytotoxic ...Continue Reading

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Citations

Feb 8, 2021·Archives of Toxicology·Rita Roque BravoDiana Dias da Silva
Mar 7, 2021·International Journal of Molecular Sciences·Avnish VermaBrian Rooney
Jul 17, 2021·Veterinary Parasitology·Rafaela de Sousa GonçalvesStella Maria Barrouin-Melo

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Methods Mentioned

BETA
sedation
protein assay

Software Mentioned

GraphPad Prism
GraphPad

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