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

• Published in: PloS one 2015-03, Vol.10 (3), p.e0121842
• Main Authors: Torina, Anali Galluce, Reichert, Karla, Lima, Fany, de Souza Vilarinho, Karlos Alexandre, de Oliveira, Pedro Paulo Martins, do Carmo, Helison Rafael Pereira, de Carvalho, Daniela Diógenes, Saad, Mário José Abdalla, Sposito, Andrei Carvalho, Petrucci, Orlando
• Format: Article
• Language: English
• Subjects: Animals; Anthraquinone; Anthraquinones - administration & dosage; Anthraquinones - pharmacology; Anti-inflammatory agents; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Blockage; Cardiology; Cardiovascular disease; Caspase; Caspase 3 - genetics; Caspase-3; Coronary vessels; Cytokines; Disease Models, Animal; Drug dosages; Fibrosis; Gene Expression Regulation - drug effects; Heart; Heart attack; Heart attacks; Heart diseases; Heart failure; Heart surgery; Hemodynamics; In vivo methods and tests; Inflammation; Inflammatory response; Interleukins; Internal medicine; Ischemia; Laboratory animals; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - etiology; Myocardial Infarction - genetics; Myocardial Infarction - pathology; NF-κB protein; Pathogenesis; Rats; Rats, Wistar; Rodents; Saline solutions; Science; Transcription Factor RelA - genetics; Tumor necrosis factor; Tumor necrosis factor-TNF; Ventricle; Ventricular Function, Left - drug effects; Ventricular Remodeling - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0121842

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. 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. 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.