Postischemic treatment by trans-resveratrol in rat liver ischemia-reperfusion: A possible strategy in liver surgery

Authors

  • Sahar Hassan-Khabbar,

    1. Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, Paris, France
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    • This work is part of the requirements for a Ph.D. at the University of Paris Descartes (S.H.-K.).

  • Charles-Henry Cottart,

    1. Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, Paris, France
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  • Dominique Wendum,

    1. Université Pierre et Marie Curie–Paris 6, Paris, France
    2. Service d'Anatomie Pathologique, Hôpital Saint-Antoine, Assistance Publique–Hôpitaux de Paris, Paris, France
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  • Françoise Vibert,

    1. Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, Paris, France
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  • Jean-Pierre Clot,

    1. Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, Paris, France
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  • Jean-François Savouret,

    1. Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche S-747, Unité de Formation et de Recherche Biomédicale, Université Paris Descartes, Paris, France
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  • Marc Conti,

    1. Département de Biochimie, Hôpital Bicêtre, Assistance Publique–Hôpitaux de Paris, Le Kremlin-Bicêtre, France
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  • Valérie Nivet-Antoine

    Corresponding author
    1. Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, Paris, France
    2. Département de Biochimie, Hôpital Charles-Foix, Assistance Publique–Hôpitaux de Paris, Ivry-sur-Seine Cedex, France
    • EA 3617, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France
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    • Telephone: 33 1 53 73 97 94; FAX: 33.1.53.73.97.99


Abstract

Liver ischemia-reperfusion (I/R) injury occurs in many clinical conditions, including liver surgery and transplantation. Oxygen free radicals generated during I/R reduce endogenous antioxidant systems and contribute to hepatic injury. trans-Resveratrol (trans-3,5,4′-trihydroxystilbene) is reported to have antioxidant properties. We investigated the effect of trans-resveratrol on liver injury induced by I/R. After 1 hour of ischemia, administered 5 minutes before 3 hours of reperfusion, trans-resveratrol was hepatoprotective at a low dose (0.02 mg/kg). It significantly decreased aminotransferase levels by about 40% and improved sinusoidal dilatation. trans-Resveratrol preserved antioxidant defense by preventing total and reduced glutathione depletion caused by I/R. At 0.2 mg/kg, trans-resveratrol significantly increased glutathione reductase, Cu/Zn–superoxide dismutase, and catalase activities. However, at a high dose (20 mg/kg), trans-resveratrol became prooxidant with an aggravation of liver injury evaluated by aminotransferase release and histological analysis and associated with a depletion of total and reduced glutathione levels and a decrease of antioxidant enzyme activities. In conclusion, a prereperfusion treatment by trans-resveratrol only at low doses decreases liver injury induced by I/R by protecting against antioxidant defense failure. This administration protocol could reduce liver damage during surgery or transplantation. Liver Transpl 14:451–459, 2008. © 2008 AASLD.

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