title: Role of Akt-dependent pathway in resveratrol-mediated cardioprotection after trauma-hemorrhage.
abstract: BACKGROUND
  Resveratrol has been shown to have protective effects for patients in shock-like states, and Akt (protein kinase B) is known to play a role in pro-inflammatory events in response to injury. The aim of this study is to determine whether resveratrol provides cardioprotection mediated via an Akt-dependent pathway in trauma-hemorrhaged animals.
  
  
  METHODS
  Male Sprague-Dawley rats underwent trauma-hemorrhage and resuscitation. A single dose of resveratrol (30 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or vehicle was administered intravenously during the resuscitation. Two hours after either the trauma-hemorrhage or sham operation, the cardiac output, the positive maximal pressure increase of the left ventricle (+dP/dt(max)), and the negative maximal pressure decrease of the left ventricle (-dP/dt(max)) were measured. Cardiac myeloperoxidase (MPO) activity, interleukin (IL)-6, and intercellular adhesion molecule (ICAM)-1 levels, Akt activity, and apoptosis were measured. One-way ANOVA and Tukey's test were used for statistical analysis.
  
  
  RESULTS
  Cardiac output and ± dP/dt(max) decreased significantly after trauma-hemorrhage. Administration of resveratrol significantly improved these cardiac function parameters. Trauma-hemorrhage increased cardiac MPO activity, IL-6 levels, and ICAM-1 levels, and these parameters were significantly improved in the resveratrol-treated rats subjected to trauma-hemorrhage. Although trauma-hemorrhage decreased cardiac Akt phosphorylation (p-Akt), resveratrol treatment following trauma-hemorrhage prevented the same decrease in cardiac p-Akt. The increase in cardiac apoptosis was attenuated in rats that received resveratrol. Co-administration of wortmannin prevented the beneficial effects of resveratrol on the attenuation of pro-inflammatory responses and cardiac injury after trauma-hemorrhage.
  
  
  CONCLUSIONS
  Resveratrol attenuates cardiac injury following trauma-hemorrhage, which is, at least in part, due to its anti-inflammatory effects via Akt-dependent pathways.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yung-Fong
authors.initials: YF
authors.lastname: Tsai
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Liu
authors.forename: Ying-Tung
authors.initials: YT
authors.lastname: Lau
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006470:Hemorrhage / Q000150:complications*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D015398:Signal Transduction / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D000077191:Wortmannin; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D000730:Androstadienes; D002316:Cardiotonic Agents; D015850:Interleukin-6; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013267:Stilbenes; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol; D000077191:Wortmannin