Postischemic treatment by trans-resveratrol in rat liver ischemia-reperfusion: a possible strategy in liver surgery.
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.
Hassan-Khabbar
Sahar
S
Equipe d'Accueil 3617, Faculté de Pharmacie, Université Paris Descartes, Paris, France.
Cottart
Charles-Henry
CH
Wendum
Dominique
D
Vibert
Françoise
F
Clot
Jean-Pierre
JP
Savouret
Jean-François
JF
Conti
Marc
M
Nivet-Antoine
Valérie
V
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006499:Hepatic Artery; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D014665:Vasodilator Agents; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D000077185:Resveratrol