Sulforaphane protects from myocardial ischemia-reperfusion damage through the balanced activation of Nrf2/AhR

Free Radic Biol Med. 2019 Nov 1:143:331-340. doi: 10.1016/j.freeradbiomed.2019.08.012. Epub 2019 Aug 15.

Abstract

The activation of the transcription factor Nrf2 and the consequent increment in the antioxidant response might be a powerful strategy to contend against reperfusion damage. In this study we compared the effectiveness between sulforaphane (SFN), a well known activator of Nrf2 and the mechanical maneuver of post-conditioning (PostC) to confer cardioprotection in an in vivo cardiac ischemia-reperfusion model. We also evaluated if additional mechanisms, besides Nrf2 activation contribute to cardioprotection. Our results showed that SFN exerts an enhanced protective response as compared to PostC. Bot, strategies preserved cardiac function, decreased infarct size, oxidative stress and inflammation, through common protective pathways; however, the aryl hydrocarbon receptor (AhR) also participated in the protection conferred by SFN. Our data suggest that SFN-mediated cardioprotection involves transient Nrf2 activation, followed by phase I enzymes upregulation at the end of reperfusion, as a long-term protection mechanism.

Keywords: Aryl hydrocarbon receptor; Ischemia-reperfusion injury; Nrf2 activation; Post-conditioning; Sulforaphane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Isothiocyanates / pharmacology*
  • Male
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Nitrosative Stress
  • Oxidative Stress*
  • Protective Agents / pharmacology
  • Rats, Wistar
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction
  • Sulfoxides

Substances

  • Anticarcinogenic Agents
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Protective Agents
  • Receptors, Aryl Hydrocarbon
  • Sulfoxides
  • sulforaphane