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

It has been previously reported that Toll:like receptor 4 (TLR4)/NF-kappa B signaling mediates early inflammation during myocardial ischemia and reperfusion. It has additionally been suggested that resveratrol produces cardioprotective and anti-inflammatory effects. The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF-kappa B signaling, reduce neutrophil accumulation and TNF-alpha 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 + L-NAME. The data showed that following MI/R, the expression of myocardial TLR4 and NF-kappa B increased significantly in the area of induced ischemia. As compared with MI/R, resveratrol significantly attenuated the expression of TLR4 and NF-kappa B and reduced the levels of myeloperoxidase, serum and myocardial TNF-alpha production, myocardial infarct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L-NAME, a nitric oxide (NO) synthase inhibitor. These data provide evidence that resveratrol inhibits TLR4/NF-kappa B signaling in the rat heart subjected to MI/R, and the anti-inflammatory effect of resveratrol is associated with NO production.