title: Protective role of Osthole on myocardial cell apoptosis induced by doxorubicin in rats.
abstract: OBJECTIVE
  To explore the effect of Osthole on protecting myocardial cell apoptosis induced by doxorubicin during cardiac failure in rats.
  
  
  METHODS
  Myocardial cells isolated from the newborn SD rats were separated into three groups: cells treated with 1 μmol doxorubicin, cells treated with Osthole at three concentrations of 10, 20, and 40 μmol, cells treated neither with Osthole nor with doxorubicin were the control groups. Consequently, cell apoptosis of myocardial cells in each group was analyzed using TUNEL assay. Also, expressions of oxidase, NADPH, and ROS in myocardial cells were analyzed using different biological methods. Moreover, expressions of cell apoptosis associated proteins were analyzed using Western blotting.
  
  
  RESULTS
  Compared with the controls, the results showed that cells received Osthole and doxorubicin treatments performed high percentage of cell apoptosis, suggesting that Osthole could anesis myocardial cell apoptosis induced by doxorubicin (P<0.05). Osthole of 10 μmol depressed the expressions of cell apoptosis associated proteins including Caspase-3 and Cytc, and enhancing expression of Bcl-XL expression (P<0.05). Osthole of 20 μmol significantly decreased the generation of intracellar superoxidase, NADPH, and NADPH activity in myocardial cells treated with doxorubicin (P<0.05). Moreover, Osthole of 20 μmol could significantly increase phosphorylated elF2α level in cells.
  
  
  CONCLUSIONS
  Our study suggested that Osthole may play a protective role in suppressing myocardial apoptosis induced by doxorubicin through inhibiting NADPH and superoxidase production and downstream phosphorylated elF2α.
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital Zhengzhou, China.
authors.forename: Hongdang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Cardiac Intensive Care Unit, Zhengzhou University People's Hospital Zhengzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Breast, Zhengzhou University Cancer Hospital Zhengzhou, China.
authors.forename: Mengwei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Breast, Zhengzhou University Cancer Hospital Zhengzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Zhengzhou University People's Hospital Zhengzhou, China.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Gao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D066126:Cardiotoxicity; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; C494813:Bcl2l1 protein, rat; D003374:Coumarins; D015852:Eukaryotic Initiation Factor-2; D051020:bcl-X Protein; D013481:Superoxides; D009249:NADP; D004317:Doxorubicin; D045304:Cytochromes c; D019255:NADPH Oxidases; C505410:Casp3 protein, rat; D053148:Caspase 3; C046627:osthol
keywords: Myocardial cells; cardioprotection; cell apoptosis; doxorubicin; osthole