title: Tropisetron attenuates cardiac injury in a rat trauma-hemorrhage model.
abstract: Tropisetron is widely used for antiemesis. Recent evidence shows that tropisetron possesses anti-inflammatory properties. Protein kinase B (Akt) is known to play an important role in negating proinflammatory response in injury. The aim of this study was to determine whether tropisetron provides cardioprotection mediated via an Akt-dependent pathway in trauma-hemorrhaged animals. Male Sprague-Dawley rats underwent trauma-hemorrhage and resuscitation. Tropisetron (1 mg/kg) with or without a PI3K inhibitor (wortmannin, 1 mg/kg) or vehicle was administered intravenously during the resuscitation. At 24 h after either the trauma-hemorrhage or sham operation, the cardiac function parameters (cardiac output, left ventricle pressure variability) were measured. Cardiac myeloperoxidase activity, interleukin 6 and intercellular adhesion molecule 1 levels, Akt activity, and apoptosis were measured. One-way analysis of variance and Tukey test were used for statistical analysis. Cardiac function was depressed and cardiac myeloperoxidase activity, interleukin 6 and intercellular adhesion molecule 1 levels, and cardiac apoptosis were markedly increased after trauma-hemorrhage. Administration of tropisetron significantly improved cardiac function and proinflammatory parameters in the tropisetron-treated rats subjected to trauma-hemorrhage. The increase in cardiac apoptosis was attenuated in rats that received tropisetron. Although trauma-hemorrhage decreased cardiac Akt phosphorylation (p-Akt), tropisetron treatment prevented the same decrease in cardiac p-Akt following trauma-hemorrhage. Coadministration of wortmannin prevented the beneficial effects of tropisetron on the attenuation of proinflammatory responses and cardiac injury after trauma-hemorrhage. Tropisetron attenuates cardiac injury following trauma-hemorrhage, which is, at least in part, through Akt-dependent anti-inflammatory pathway.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Liu
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Fu-Wei
authors.initials: FW
authors.lastname: Liu
authors.forename: Huang-Ping
authors.initials: HP
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002302:Cardiac Output / Q000502:physiology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D053938:DNA Fragmentation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006335:Heart Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007211:Indoles / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077526:Tropisetron
chemical_list: D002316:Cardiotonic Agents; D007211:Indoles; D018836:Inflammation Mediators; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; D000077526:Tropisetron; D009195:Peroxidase; D051057:Proto-Oncogene Proteins c-akt