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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. Liver Transpl 14:451–459, 2008. © 2008 AASLD.