BN52021 protects rat cardiomyocyte from doxorubicin induced cardiotoxicity

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1719-24. eCollection 2015.

Abstract

The aim of this study was to assess the role of platelet activating factor (PAF) antagonist BN52021 in doxorubicin induced cardiotoxicity and to explore the mechanisms. H9c2 cardiomyocytes were employed to investigate the effect of BN52021 on doxorubicin induced cell viability and cell apoptosis. Signaling pathway of caspase 3, cytochrome c, calcium and p38 mitogen-activated protein (MAPK) was determined during the doxorubicin induced apoptosis. Our results showed BN52021 pretreatment could protected cell death induced by doxorubicin in H9c2 cardiomyocytes. Decrease concentration of [Ca(2+)] and expression of phosphorylated P38 MAPK were accounted for the protection effect. Inhibition of signaling pathway of calcium and p38 MAPK showed similar effect exerted by BN52021 in doxorubicin induced cell apoptosis. Our results demonstrated BN52021 protected against doxorubicin induced cell death in H9c2 cardiomyocytes by calcium and p38 MAPK signaling in vitro. These finding may give insight on the treatment of doxorubicin induced cardiomyopathy.

Keywords: BN52021; MAPK signaling; calcium signaling; cardiotoxicity; doxorubicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / toxicity
  • Apoptosis / drug effects
  • Blotting, Western
  • Cardiomyopathies / chemically induced
  • Cardiotoxicity
  • Cell Line
  • Cell Survival / drug effects
  • Doxorubicin / toxicity
  • Ginkgolides / pharmacology*
  • In Situ Nick-End Labeling
  • Myocytes, Cardiac / drug effects*
  • Platelet Activating Factor / antagonists & inhibitors*
  • Rats

Substances

  • Antibiotics, Antineoplastic
  • Ginkgolides
  • Platelet Activating Factor
  • Doxorubicin