Early reductive stress and late onset overexpression of antioxidant enzymes in experimental myocardial infarction

Autores de INCLIVA

• Aitor Carretero Martínez

  Autor

• 

  Maria Carmen Gomez Cabrera

  Autor

• César Rios Navarro

  Autor

• Andrea Salvador Pascual

  Autor

• 

  Vicent Bodí Peris

  Autor

• 

  Jose Viña Ribes

  Autor

Grupos y Plataformas de I+D+i

• Grupo de Investigación en Ejercicio, Nutrición y Estilo de Vida Saludable

  

  Established Researcher

  Maria Carmen Gomez Cabrera

• Grupo de investigación en envejecimiento y ejercicio físico

  

  Leading Researcher

  Jose Viña Ribes

• Grupo de Investigación Traslacional en Cardiopatía Isquémica

  

  Leading Researcher

  Vicent Bodí Peris

Abstract

Reductive stress is defined as a pathophysiological situation in which the cell becomes more reduced than in the normal, resting state. It represents a disturbance in the redox state that is harmful to biological systems. Our aim was to study the occurrence of reductive stress in the early phases of experimental myocardial infarction and to determine the mechanisms leading to such stress using a swine model. During the ischemic period, we found a decrease in the oxidized to reduced glutathione ratio (GSSG/GSH) (0.7-0.3), in the lactate to pyruvate ratio (42.7-132.4), in protein glutathionylation (111.8-96.1), and in p38 phosphorylation (0.9-0.4). This was accompanied by a significant increase in the expression of Thioredoxin (TXN) (0.6-1.9) and peroxiredoxin (PRDX6) (0.6-1.6) in different left ventricle areas. After reperfusion, there was a massive increase in oxidative damage markers including lipid peroxidation (0.2-0.4), protein carbonylation (144.9-462.8), and glutathionylation (111.8-176.8). Concomitantly, we found an activation of nuclear factor erythroid 2-related factor 2 (Nrf2) (1.2-6.1) and of a set of antioxidant enzymes including TXN, PRDX6, glutathione peroxidase (GPX1), glutathione reductase (GSR), and glucose 6 phosphate dehydrogenase (G6PD). We describe an early reductive, followed by a late onset oxidative stress (1 week and 1 month after reperfusion) in a swine myocardial infarction model. The occurrence of an early reductive phase may explain the lack of effectiveness of antioxidant therapies when administered in the early phases after reperfusion of ischemic hearts.

Keywords

• Antioxidant enzymes; ischemia-reperfusion; oxidative damage