Attenuation of ischemia/reperfusion injury in rats by the anti-inflammatory action of resveratrol.

Abstract

Resveratrol (trans-3,4',5-trihydroxystilbene, CAS 501-36-0), a natural antioxidant and polyphenol found in grapes and wine, has been found to pharmacologically precondition the heart in nitric oxide (NO)-dependent manner. In the vascular system, NO functions as an endogenous inhibitor of leukocyte chemotaxis, adherence, and activation. The present study was designed to determine if resveratrol, through NO, can block the proadhesive molecules generated in the ischemic reperfused myocardium. Isolated hearts were prepared from properly anesthetized rats, and mounted on a Langendorff apparatus. The hearts were randomly assigned to one of the three groups: (i) control, (ii) resveratrol, and (iii) resveratrol + NG-nitro-L-arginine ethyl ester (L-NAME). The hearts were perfused in the absence (n = 6) or presence of 10 micromol/L resveratrol (n=6) or resveratrol + L-NAME (n = 6) for 15 min. All the hearts were then subjected to 30 min ischemia followed by 2 h of reperfusion. Ventricular function was monitored, infarct size and apoptotic cell death measured, and the proadhesive molecules and malonaldehyde formation determined in the perfusate. Resveratrol significantly improved postischemic ventricular function and reduced myocardial infarct size compared to the non-treated control group. The amount of proadhesive molecules including soluble intracellular adhesion molecule-1 (sICAM-1), endothelial leukocyte adhesion molecule-1 (sE-Selectin) and vascular cell adhesion molecule-1 (sVCAM-1) were each significantly decreased during reperfusion in the resveratrol group. L-NAME, a NO blocker, completely abolished such beneficial effects of resveratrol. The results support an anti-inflammatory action of resveratrol through a NO-dependent mechanism.

• Authors: Samarjit Das, Mario Falchi, Aldo Bertelli, Nilanjana Maulik, Dipak K Das
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 56 Issue 10 Pg. 700-6 ( 2006) ISSN: 0004-4172 [Print] Germany
• PMID: 17225566 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cell Adhesion Molecules
• RNA, Messenger
• Stilbenes
• Nitric Oxide
• Malondialdehyde
• Nitric Oxide Synthase Type II
• Resveratrol

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Apoptosis (drug effects)
• Blood Pressure (drug effects)
• Cell Adhesion Molecules (metabolism)
• Enzyme Induction (drug effects)
• Heart Function Tests
• In Situ Nick-End Labeling
• Male
• Malondialdehyde (metabolism)
• Myocardial Infarction (pathology)
• Myocardial Reperfusion Injury (drug therapy, pathology)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase Type II (biosynthesis)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Resveratrol
• Stilbenes (therapeutic use)