Postischemic Treatment bytrans-Resveratrol in Rat Liver... : Liver Transplantation (original) (raw)

Original Articles

Postischemic Treatment by trans -Resveratrol in Rat Liver Ischemia-Reperfusion: a Possible Strategy in Liver Surgery

Hassan-Khabbar, Sahar1; Cottart, Charles-Henry1; Wendum, Dominique2,3; Vibert, Françoise1; Clot, Jean-Pierre1; Savouret, Jean-François4; Conti, Marc5; Nivet-Antoine, Valérie1,6

1_Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, Paris, France_

2_Université Pierre et Marie Curie–Paris 6, Paris, France_

3_Service d'Anatomie Pathologique, Hôpital Saint-Antoine, Assistance Publique–Hôpitaux de Paris, Paris, France_

4_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_

5_Département de Biochimie, Hôpital Bicêtre, Assistance Publique–Hôpitaux de Paris, Le Kremlin-Bicêtre, France_

6_Département de Biochimie, Hôpital Charles-Foix, Assistance Publique–Hôpitaux de Paris, Ivry-sur-Seine Cedex, France_

Address reprint requests to Valérie Nivet-Antoine, Ph.D., EA 3617, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France. Telephone: 33 1 53 73 97 94; FAX: 33.1.53.73.97.99; Email: [email protected]

Received June 1 2007; accepted 29 October 2007

Published online in Wiley InterScience (wileyonlinelibrary.com).

This work is part of the requirements for a Ph.D. at the University of Paris Descartes (S.H.-K.).

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.