Diacerein improves left ventricular remodeling and cardiac function by reducing the inflammatory response after myocardial infarction

PLoS One. 2015 Mar 27;10(3):e0121842. doi: 10.1371/journal.pone.0121842. eCollection 2015.

Abstract

Background: The inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo.

Methods and results: Ligation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-κB) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-κB p65 transcription.

Conclusions: Treatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-κB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthraquinones / administration & dosage*
  • Anthraquinones / pharmacology
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Caspase 3 / genetics
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / etiology
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology*
  • Rats
  • Rats, Wistar
  • Transcription Factor RelA / genetics
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects

Substances

  • Anthraquinones
  • Anti-Inflammatory Agents
  • Rela protein, rat
  • Transcription Factor RelA
  • diacerein
  • Casp3 protein, rat
  • Caspase 3

Grants and funding

This work was funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), grant number 2011/14550-7.