Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury

Background: Resveratrol has been shown to attenuate reactive oxygen species formation and protect against ischemia-reperfusion (I/R) injury. However, the effects of resveratrol against subacute intestinal I/R injury are not clearly elucidated. Therefore, this study was designed to investigate the effects and possible protective mechanisms of resveratrol on subacute intestinal I/R injury in mice. Methods: BALB/c mice were subjected to 1 h ischemia by occluding the superior mesenteric artery and 24 h reperfusion. Histologic injury; myeloperoxidase, superoxide dismutase, and glutathione peroxidase activity; malondialdehyde level; inducible nitric oxide synthase (iNOS), Ac-NF-kappa Bp65, and sirtuin 1 (SIRT1) expression; NF-kappa B translocation; and nitric oxide (NO) production were examined in treated with or without resveratrol in the absence or presence of pharmacologic inhibitors. Results: Resveratrol significantly ameliorated subacute intestinal I/R injury accompanied with the decrease of NO production as well as iNOS expression. In addition, resveratrol obviously upregulated the expression of SIRT1 and inhibited the activity of NF-kappa B. After application of iNOS inhibitor S-methylisothiourea and NF-kappa B inhibitor pyrrolidine dithiocarbamate, the protective effect of resveratrol was significantly augmented by attenuating iNOS and NO production, indicating that resveratrol exerted its protective effect on intestinal I/R injury via NF-kappa B-mediated iNOS pathway. Furthermore, the protective effect of resveratrol was correlated with SIRT1, because application of SIRT1 inhibitor nicotinamide strikingly weakened the protective effect of resveratrol. Conclusions: Taken together, our findings showed that resveratrol protects intestinal subacute I/R injury via the SIRT1-NF-kappa B pathway in an iNOS-NO-dependent manner. Therefore, resveratrol has a potential clinical prospect for further development of anti-injury therapy. (C) 2013 Elsevier Inc. All rights reserved.