title: Sevoflurane ameliorates doxorubicin-induced myocardial injury by affecting the phosphorylation states of proteins in PI3K/Akt/mTOR signaling pathway.
abstract: BACKGROUND
  The effect of sevoflurane on the doxorubicin-induced myocardial injury was explored by investigating the phosphorylation states of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt/mam-malian target of rapamycin (mTOR) signaling pathway.
  
  
  METHODS
  Myocardial injury rat models were induced by doxorubicin and evenly assigned into five groups according to different treatment: Doxorubicin group (DG, 200-μL saline solution), sevoflurane group (SevG, inhaled with 2.4% sevoflurane for 2 h), LY294002 group (LYG, Akt inhibitor, 0.3 mg/kg in 200-μL Dimethyl Sulfoxide [DMSO]), solvent DMSO control group (SG) and autophagy inhibitor 3-methyladenine (3-MA) group (MG, 30 mg/kg in 200-μL DMSO). The healthy rats were assigned to a contro1 group (CG, 200-μL saline solution). Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The concentration of cardiac troponin I (cTnI) was detected by ELISA. The levels of total Akt (t-Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated-mTOR (p-mTOR) and autophagy marker LC3-II was detected by Western Blot. The experiments were also repeated at the cell level.
  
  
  RESULTS
  Terminal deoxynucleotidyl transferase dUTP nick end labeling analysis showed that the ap-optosis rates were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG. The levels of p-Akt p-mTOR were low in groups DG and SG, reached the lowest level in LYG, increased in SevG and MG, and reached the highest level in CG. In contrast, LC3-II expression, apoptosis index and serum cTnI concentration were high in DG and SG, reached the highest level in LYG, reduced in SevG and MG, and reached the lowest level in CG (p < 0.05). Cell experiment showed similar results as with animal experiments.
  
  
  CONCLUSIONS
  Sevoflurane ameliorates myocardial injury by affecting the phosphorylation states of the proteins in PI3K/Akt/mTOR signaling pathway and reducing the injury biomarker. (Cardiol J 2017; 24, 4: 409-418).
authors.forename: Yini
authors.initials: Y
authors.lastname: Wu
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yu
authors.forename: Dongli
authors.initials: D
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of General surgery,Wenzhou Medical College, the fifth Affiliated Hospital. fanlihua19@126.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D066126:Cardiotoxicity; D002460:Cell Line; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004317:Doxorubicin; D006331:Heart Diseases / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D019210:Troponin I / Q000378:metabolism
chemical_list: D008738:Methyl Ethers; D020011:Protective Agents; D019210:Troponin I; D000077149:Sevoflurane; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; C546845:mTOR protein, rat; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D052279:Creatine Kinase, MB Form
keywords: cardiac injury; doxorubicin; phosphatidylinositol 3-kinase; phosphorylated rapamycin; protein-serine-threonine kinases