Anti-apoptotic and myocardial protective effects of ethyl pyruvate after regional ischaemia/reperfusion myocardial damage in an in vivo rat model

Singapore Med J. 2017 Sep;58(9):557-561. doi: 10.11622/smedj.2016190. Epub 2016 Dec 20.


Introduction: The integration of reactive oxygen species is strongly associated with important pathophysiological mechanisms that mediate myocardial ischaemia/reperfusion (I/R) damage. Pyruvate is an efficacious scavenger of reactive oxygen species and a previous study has shown that ethyl pyruvate (EP) has a myocardial protective effect against regional I/R damage in an in vivo rat model. The purpose of this study was to determine whether the myocardial protective effect of EP is associated with anti-apoptosis.

Methods: Rats were allocated to receive EP dissolved in lactated Ringer's solution or lactated Ringer's solution alone, via intraperitoneal infusion one hour before ischaemia. They were exposed to 30 minutes of ischaemia followed by reperfusion of the left coronary artery territory over two hours. Anti-apoptotic effects were checked using several biochemical parameters after two hours of reperfusion. Apoptosis was analysed using measured caspase-3 activity, Western blotting of B-cell lymphoma 2 (Bcl-2) family protein cleaved by caspase-3, and assessment of DNA laddering patterns and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining test.

Results: In ischaemic myocardium, EP increased Bcl-2 expression, but reduced Bcl-2-associated X protein and cleaved caspase-3 expressions. EP reduced the expression of DNA laddering and the number of myocardial I/R-damaged TUNEL-positive cells.

Conclusion: This study demonstrated that EP has an anti-apoptotic effect after regional I/R damage in an in vivo rat heart model. The myocardial protective effect of EP may be related to its anti-apoptotic effect.

Keywords: apoptosis; ethyl pyruvate; myocardium; reperfusion injury.

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3 / metabolism
  • DNA Fragmentation
  • Disease Models, Animal
  • Male
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardium / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyruvates / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • bcl-2-Associated X Protein / metabolism


  • Bax protein, rat
  • Bcl2 protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • Pyruvates
  • bcl-2-Associated X Protein
  • ethyl pyruvate
  • Casp3 protein, rat
  • Caspase 3