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Protective effect of post-ischemic treatment with trans-resveratrol on cytokine production and neutrophil recruitment by rat liver
Authors:Sahar Hassan-Khabbar,Michel Vamy,Charles-Henry Cottart,Dominique Wendum,Franç  oise Vibert,Jean-Franç  ois Savouret,Patrice Thé  rond,Jean-Pierre Clot,Anne-Judith Waligora,Valé  rie Nivet-Antoine
Affiliation:1. Equipe d''Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l''Observatoire, 75006 Paris, France;2. Département de Biochimie, Hôpital Charles-Foix, Assistance Publique-Hôpitaux de Paris, Paris, France;3. Université Pierre et Marie Curie-Paris 6, Paris, France;4. Service d''Anatomie Pathologique, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France;5. INSERM, Unité Mixte de Recherche S-747, Unité de Formation et de Recherche Biomédicale, Université Paris Descartes, Paris, France;6. Service de Biochimie, Centre Hospitalier de Versailles, Le Chesnay, France;g Equipe d''Accueil 4065, Faculté de Pharmacie, Université Paris Descartes, Paris, France;h Equipe d''Accueil 2510, Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l''Observatoire, Paris, France
Abstract:Oxidative and inflammatory processes are elicited during hepatic post-ischemic reperfusion and generate liver damage. This study investigated the early anti-inflammatory effect of trans-resveratrol (T-res) and its consequences on the late self-aggravating inflammatory process in liver ischemia-reperfusion (I/R). Partial hepatic ischemia was initiated in rats for 1 h and T-res (0.02 and 0.2 mg/kg) was administered intravenously 5 min before starting reperfusion for 3 h. Plasma levels of aminotransferases and cytokines (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6) and hepatic neutrophil recruitment were assessed. Hepatic expression of stress protein (heat-shock protein (HSP-70), heme oxygenase-1(HO-1)) and cytokine (TNF-α, IL-1β, keratinocyte chemoattractant (KC)) mRNA was investigated. I/R caused an increase in aminotransferase levels and increased polymorphonuclear cell infiltration. Post-ischemic treatment with T-res (0.02 and 0.2 mg/kg) resulted in a significant decrease in aminotransferase, IL-1β and IL-6 plasma levels by about 40%, 60% and 40%, respectively, compared to the vehicle I/R group. Post-ischemic treatment with T-res (0.02 mg/kg) also significantly decreased hepatic neutrophil recruitment. TNF-α, IL-1β, KC and HO-1 hepatic mRNA expression was reduced by T-res without any change in HSP-70 mRNA. This T-res mediated decrease in early release of cytokines and neutrophil recruitment led to a reduction in the late inflammatory process. T-resveratrol might be useful in the prevention of inflammation secondary to hepatic surgery or liver transplantation.
Keywords:Heat-shock protein   TNF-α   IL-1β   KC   Oxidative stress
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