Edaravone protects rats against oxidative stress and apoptosis in experimentally induced myocardial infarction: Biochemical and ultrastructural evidence

Redox Rep. 2015;20(6):275-81. doi: 10.1179/1351000215Y.0000000011. Epub 2015 Apr 20.

Abstract

Objectives: The present study was designed to evaluate the cardioprotective potential of edaravone on oxidative stress, anti-apoptotic, anti-inflammatory and ultrastructure findings in isoproterenol (ISO) induced myocardial infarction (MI) in rats.

Methods: Rats were pretreated with edaravone (1, 3, 10 mg/kg body weight-1 day-1) intraperitoneally. MI was induced by subcutaneous administration of ISO (85 mg/kg body weight-1) at two doses with 24h interval.

Results: ISO treated rats showed significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and decreased levels of reduced glutathione, glutathione perdoxidase, glutathione reductase and glutathione-S- transferase in the cardiac tissues. Moreover, significant increase in the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), C--reactive protein and caspase-3 activity was observed in ISO treated group. Pretreatment of ISO intoxicated rats with edaravone showed significant decrease in the level of TBARS, increased activities of antioxidant enzymes and significantly decreased levels of LDH and CK-MB. Moreover, results also showed decreased C-reactive protein level, caspase-3 activity and maintained ultrastructure of the myocardial cells.

Discussion: Our study suggests that edaravone possess strong cardioprotective potential. Edaravone may have exhibited cardioprotective effects by restoring antioxidant defense mechanism, maintaining integrity of myocardial cell membrane, reducing apoptosis and inflammation against ISO induced MI and associated oxidative stress.

Keywords: C-reactive protein; Caspase-3; Edaravone; Isoproterenol; Myocardial infarction; Oxidative stress; Ultrastructure evaluation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antipyrine / analogs & derivatives*
  • Antipyrine / therapeutic use
  • Apoptosis*
  • C-Reactive Protein / metabolism
  • Caspase 3 / metabolism
  • Creatine Kinase, MB Form / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Edaravone
  • Free Radical Scavengers / therapeutic use
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Glutathione Transferase / metabolism
  • Heart / drug effects
  • Inflammation
  • Isoproterenol / chemistry
  • L-Lactate Dehydrogenase / metabolism
  • Myocardial Infarction / blood*
  • Myocardial Infarction / drug therapy*
  • Myocardium / metabolism
  • Myocardium / ultrastructure
  • Oxidative Stress*
  • Rats
  • Rats, Wistar
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Thiobarbituric Acid Reactive Substances
  • C-Reactive Protein
  • L-Lactate Dehydrogenase
  • Glutathione Peroxidase
  • Glutathione Reductase
  • Glutathione Transferase
  • Creatine Kinase, MB Form
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione
  • Isoproterenol
  • Edaravone
  • Antipyrine