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  • Title: Role of Akt-dependent pathway in resveratrol-mediated cardioprotection after trauma-hemorrhage.
    Author: Tsai YF, Liu FC, Lau YT, Yu HP.
    Journal: J Surg Res; 2012 Jul; 176(1):171-7. PubMed ID: 21764074.
    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. CONCLUSION: Resveratrol attenuates cardiac injury following trauma-hemorrhage, which is, at least in part, due to its anti-inflammatory effects via Akt-dependent pathways.
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