Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction Alexandre Luz de Castro a , Angela Vicente Tavares a , Cristina Campos a , Rafael Oliveira Fernandes a , Rafaela Siqueira a , Adriana Conzatti a , Amanda M. Bicca a , Tânia Regina G. Fernandes a , Carmem L. Sartório a , Paulo Cavalheiro Schenkel b , Adriane Belló-Klein a , Alex Sander da Rosa Araujo a,⇑ a Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil b Departamento de Fisiologia e Farmacologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil article info Article history: Received 17 September 2013 Received in revised form 17 April 2014 Accepted 18 April 2014 Available online 28 April 2014 Keywords: T3 T4 Redox balance Reactive oxygen species abstract Reactive oxygen species (ROS) are involved with progression from infarction to heart failure. Studies show that thyroid hormones (TH) present cardioprotective effects. This study aims to evaluate whether TH effects after infarction are associated to redox balance modulation. Male Wistar rats were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT), and infarcted + TH (AMIT). During 26 days, animals received T3 (2 lg/100 g/day) and T4 (8 lg/100 g/day) by gavage. Echocardiographic parameters were assessed and heart tissue was collected to biochemical analysis. AMIT rats presented absence of lung congestion, less cardiac dilatation, and normalization in myocardial performance index, compared with AMI. AMI rats presented an increase in hydrogen peroxide levels and in lipid peroxidation and a decrease in GSH/GSSG. TH prevented these alterations in AMIT. In conclusion, TH seem to reduce the levels of ROS, preventing oxidative stress, and improving cardiac function in infarcted rats. Ó 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Several studies have shown that reactive oxygen species (ROS) are involved in the process of cardiac remodeling after acute myo- cardial infarction (Schenkel et al., 2012; 2010; Singal et al., 1999). As early as 48 h after the ischemic event, there is evidence of changes in oxidative stress parameters in the myocardial tissue (Tavares et al., 2012). After injury, neurohumoral mechanisms start to act in order to maintain cardiac function and the heart goes into a compensated stage of hypertrophy (Francis et al., 2001). In this phase, cellular antioxidant reserve increases (Singal et al., 1999). However, in a decompensated stage of heart muscle, this reserve is reduced, resulting in the occurrence of oxidative stress (Singal et al., 1999). This was demonstrated in experimental models of acute myocardial infarction, 28 days after the ischemic insult (Schenkel et al., 2010). In this work, the reduction in the fractional area change of the heart was positively correlated with a decrease in the reduced to oxidized glutathione ratio (GSH/GSSG) in heart tissue (Schenkel et al., 2010). It has been recently shown that thyroid hormones may present a protective effect after myocardial infarction (Forini et al., 2011; Mourouzis et al., 2013b; Pantos et al., 2008; 2007). In a heart fail- ure stage, plasma levels of these hormones decrease and/or the expression of both thyroid hormone receptors (TRs), TRa, and TRb, in the myocardium decreases (Forini et al., 2011; Pantos et al., 2011). This scenario is detrimental for the heart, since these receptors, especially TRa1, seem to be relevant for the cardiomyo- cytes response against stress (Mourouzis et al., 2013a). Based on this, many studies have evaluated the hypothesis that the admin- istration of thyroid hormones could exert beneficial effects on the heart (Forini et al., 2011; Mourouzis et al., 2013b; Pantos et al., 2008; 2007). Treatment with T3 and T4, in the post- infarction period, could prevent the development of tissue hypothyroidism and, thereby, mitigate deleterious changes in the cardiac tissue (Pantos et al., 2011; 2010a,b). The main mechanism through which thyroid hormones could promote a cardioprotective effect is by a genomic action, involving the binding of these hor- mones to its intracellular receptors and the modulation of protein synthesis in the cardiomyocyte (Pantos et al., 2011; 2010a,b). T3 and T4 administration, after myocardial infarction, could reduce http://dx.doi.org/10.1016/j.mce.2014.04.010 0303-7207/Ó 2014 Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author. Address: Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, sala 01, CEP 90050170, Porto Alegre, RS, Brazil. Tel.: +55 (51) 3308 3621; fax: +55 2151 33083656. E-mail address: alsanderaraujo@hotmail.com (A.S. da Rosa Araujo). Molecular and Cellular Endocrinology 391 (2014) 22–29 Contents lists available at ScienceDirect Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce