Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-κB signaling pathway.

ABSTRACT

It has been previously reported that Toll­like receptor 4 (TLR4)/NF­κB signaling mediates early inflammation during myocardial ischemia and reperfusion. It has additionally been suggested that resveratrol produces cardioprotective and anti­inflammatory effects. The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF­κB signaling, reduce neutrophil accumulation and TNF­α induction in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to a sham operation, myocardial ischemia and reperfusion (MI/R), MI/R + resveratrol or MI/R + resveratrol + L­NAME. The data showed that following MI/R, the expression of myocardial TLR4 and NF­κB increased significantly in the area of induced ischemia. As compared with MI/R, resveratrol significantly attenuated the expression of TLR4 and NF­κB and reduced the levels of myeloperoxidase, serum and myocardial TNF­α production, myocardial infarct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L­NAME, a nitric oxide (NO) synthase inhibitor. These data provide evidence that resveratrol inhibits TLR4/NF­κB signaling in the rat heart subjected to MI/R, and the anti­inflammatory effect of resveratrol is associated with NO production.