title: BN52021 protects rat cardiomyocyte from doxorubicin induced cardiotoxicity.
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.
authors.affiliation: Department of Cardiology, Second Hospital of Jilin University, Jilin University Changchun 130041, China ; Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University Changchun 130041, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University Changchun 130041, China ; Department of Anesthesiology, First Medical Hospital of Jilin University, Jilin University Changchun 130021, China.
authors.forename: Chengluan
authors.initials: C
authors.lastname: Xuan
authors.affiliation: College of Basic Medical Sciences, Jilin University Changchun 130021, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xuan
authors.affiliation: Department of Cardiovascular Surgery, Second Hospital of Jilin University, Jilin University Changchun 130041, China.
authors.forename: Rihao
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Second Hospital of Jilin University, Jilin University Changchun 130041, China.
authors.forename: Junnan
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000139:chemically induced; D066126:Cardiotoxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity; D046934:Ginkgolides / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; D046934:Ginkgolides; D010972:Platelet Activating Factor; D004317:Doxorubicin
keywords: BN52021; MAPK signaling; calcium signaling; cardiotoxicity; doxorubicin