PMID- 17924179
OWN - NLM
STAT- MEDLINE
DCOM- 20080205
LR  - 20220311
IS  - 0920-3206 (Print)
IS  - 0920-3206 (Linking)
VI  - 21
IP  - 5
DP  - 2007 Oct
TI  - Preventive cardioprotection of erythropoietin against doxorubicin-induced 
      cardiomyopathy.
PG  - 367-74
AB  - INTRODUCTION: Doxorubicin (DOX) is a highly effective chemotherapeutic agent 
      related to dose-dependent cardiomyopathy. Recent evidence suggests that 
      erythropoietin (EPO) can play a protective role in cardiovascular diseases by 
      non-erythropoietic effects. In the present study, we tested the hypothesis that 
      EPO may protect against DOX-induced cardiomyopathy through anti-apoptotic 
      mechanisms both in vitro and in vivo. MATERIALS AND METHODS: Isolated neonatal 
      Wistar rat cardiomyocytes were treated with vehicle, DOX with or without EPO, or 
      EPO. Twenty-four hours later, the cells were used to determine cardiomyocyte 
      apoptosis (TUNEL assay). Cardiomyopathy was induced in Wistar rats by 
      intraperitoneal injections (IP) of DOX (2.5 mg/kg, six times for 2 weeks). EPO 
      (2,500 U/kg, six times for 2 weeks) was administered simultaneously in the 
      DOX+EPO group and the EPO group. Two weeks after the last administration, cardiac 
      function was evaluated by echocardiography and invasive haemodynamic 
      measurements. Rats were then sacrificed for histological and TUNEL analyses, with 
      immunological detection for cardiac Troponin-T (cTnT), alpha-actinin, Bax and 
      Bcl-2. RESULTS: EPO significantly ameliorated DOX-induced apoptosis of cultured 
      cardiomyocytes as demonstrated by TUNEL assay. In the rat model, cardiac function 
      significantly decreased in the DOX group. In contrast, the DOX+EPO group showed 
      considerable improvement in cardiac function, inhibition of cardiomyocyte 
      apoptosis, reduction of fibrosis, as well as up-regulation of Bcl-2 protein 
      expression. CONCLUSIONS: Our results suggest that EPO exerts preventive 
      cardioprotective effects on DOX-induced cardiomyopathy via anti-apoptotic 
      pathways. The up-regulation of Bcl-2 protein expression may contribute to this.
FAU - Chen, Xing
AU  - Chen X
AD  - Department of Cardiology, General Hospital of Tianjin Medical University, 
      Tianjin, China.
FAU - Chen, Yongli
AU  - Chen Y
FAU - Bi, Yanyong
AU  - Bi Y
FAU - Fu, Naikuan
AU  - Fu N
FAU - Shan, Chunyan
AU  - Shan C
FAU - Wang, Sili
AU  - Wang S
FAU - Aslam, Shahid
AU  - Aslam S
FAU - Wang, Peixian Wang
AU  - Wang PW
FAU - Xu, Jing
AU  - Xu J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cardiovasc Drugs Ther
JT  - Cardiovascular drugs and therapy
JID - 8712220
RN  - 0 (Bax protein, rat)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Troponin T)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 11003-00-2 (Actinin)
RN  - 11096-26-7 (Erythropoietin)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Actinin/analysis/biosynthesis
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Cardiomyopathies/chemically induced/pathology/*prevention & control
MH  - Cardiotonic Agents/*therapeutic use
MH  - Disease Models, Animal
MH  - Doxorubicin/*toxicity
MH  - Echocardiography
MH  - Erythropoietin/*therapeutic use
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling/methods
MH  - Male
MH  - Proto-Oncogene Proteins c-bcl-2/analysis/biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Troponin T/analysis/biosynthesis
MH  - bcl-2-Associated X Protein/analysis/biosynthesis
EDAT- 2007/10/10 09:00
MHDA- 2008/02/06 09:00
CRDT- 2007/10/10 09:00
PHST- 2007/10/10 09:00 [pubmed]
PHST- 2008/02/06 09:00 [medline]
PHST- 2007/10/10 09:00 [entrez]
AID - 10.1007/s10557-007-6052-0 [doi]
PST - ppublish
SO  - Cardiovasc Drugs Ther. 2007 Oct;21(5):367-74. doi: 10.1007/s10557-007-6052-0.