title: Protective effect of erythropoietin on myocardial apoptosis in rats exposed to carbon monoxide.
abstract: OBJECTIVE
  Cardiac complications are common in carbon monoxide (CO) poisoning and associated with high morbidity and mortality. We have previously shown that erythropoietin (EPO) could reduce CO-induced cardiac ischemia in rat. In the current study, the anti-apoptotic effect of EPO during CO cardiotoxicity was investigated in order to elucidate the mechanism of EPO anti-ischemic action.
  
  
  METHODS
  Wistar rats were exposed to CO (250, 1000 and 3000ppm). EPO (5000IU/kg) was administered to all groups by intraperitoneal injection at the end of CO exposure period. TUNEL and caspase-3 activity levels were assessed to investigate the effects of CO exposure and subsequent EPO administration on myocardial apoptosis. The changes of mitochondrial membrane potential (MMP) were also assessed with sensitive lipophilic dye JC-1 by flow cytometry. The roles of Bcl2 and Bax in EPO protective effect were investigated by Western blotting.
  
  
  RESULTS
  Myocardial apoptosis was observed following CO exposure. Moreover, mitochondrial membrane depolarization and significant reduction in Bcl2/Bax ratio were shown following CO poisoning especially at 3000ppm. On the other hand, EPO administration could effectively suppress apoptosis in myocardial cells. Also, EPO significantly prevented the CO-induced depolarization of MMP (p<0.001) and preserved Bcl2/Bax ratio (p<0.01).
  
  
  CONCLUSIONS
  EPO reduces myocardial injury due to CO intoxication. Thus EPO could be suggested as a possible candidate for the management of CO cardiotoxicity with clinical applications.
authors: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
authors: Mitra Asgharian
authors: MA
authors: Rezaee
authors: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Amir Hooshang
authors: AH
authors: Mohammadpour
authors: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Mohsen
authors: M
authors: Imenshahidi
authors: Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Mahmoud
authors: M
authors: Mahmoudi
authors: Immunobiochemistry Laboratory, Immunology Research Center, Bu-Ali Research Institute, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Mojtaba
authors: M
authors: Sankian
authors: Cardiology Division, General Hospital of Karditsa Perfecture, Thessaly, Greece.
authors: Konstantinos
authors: K
authors: Tsarouhas
authors: Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Greece.
authors: Andreas
authors: A
authors: Tsakalof
authors: Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Greece.
authors: Aristidis Micheal
authors: AM
authors: Tsatsakis
authors: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: moallem@mums.ac.ir.
authors: Seyed Adel
authors: SA
authors: Moallem
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002248:Carbon Monoxide / Q000633:toxicity*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D002248:Carbon Monoxide
keywords: Bcl2; Carbon monoxide; Erythropoietin; Myocardial apoptosis