Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury: role of Nrf2/ARE pathway

Abstract

The protective role of resveratrol in myocardial ischemia/reperfusion is not well understood. The aim of this study was to investigate whether resveratrol modulates inflammation and oxidative stress and the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to sham operation, myocardial ischemia/reperfusion (MI/R) alone, and MI/R + resveratrol. The results demonstrated that compared to MI/R, resveratrol improved cardiac function, reduced myocardial infarction area, myocardial myeloperoxidase (MPO) levels, serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels. Resveratrol also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reduced the level of malondialdehyde (MDA) in MI/R rats. Resveratrol also enhanced levels of Nrf2 and heme oxygenase-1. In summary, these results demonstrated that resveratrol exerted significant antioxidant and cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.

Keywords: HO-1; MDA; Nrf-2; Resveratrol; SOD; myocardial ischemia/reperfusion injury.

Figures

Figure 1

Effect of resveratrol on cardiac function. A. The effect of resveratrol on LVEDP. B. The effect of resveratrol on LVEF. C. The effect of resveratrol on +dp/dx max. D. The effect of resveratrol on -dp/dx max. LVEF, left ventricle ejection fraction; LVEDP, left ventricle end-diastolic pressure. Data were expressed as mean ± SD (n = 10 in each group). *P < 0.05 versus the sham group, #P < 0.05 versus MI/R group.

Figure 2

Effect of resveratrol on the myocardial infarction area induced by MI/R. Data were expressed as mean ± SD (n = 10 in each group). *P < 0.05 versus the sham group, #P < 0.05 versus MI/R group.

Figure 3

The comparison of CK activity in each group. The CK activity in the sham group was relatively lower, while the CK activity in MI/R group was significantly increased, which was inhibited by resveratrol. Data were expressed as mean ± SD (n = 10 in each group). *P < 0.05 versus the sham group, #P < 0.05 versus MI/R group.

Figure 4

The comparison of LDH activity in each group. The LDH activity in the sham group was relatively lower, while the LDH activity in MI/R group was significantly increased, which was inhibited by resveratrol. Data were expressed as mean ± SD (n = 10 in each group). *P < 0.05 versus the sham group, #P < 0.05 versus MI/R group.

Figure 5

The comparison of MPO activity in each group. The MPO activity in the sham group was relatively lower, while the MPO activity in MI/R group was significantly increased, which was blocked by resveratrol. Data were expressed as mean ± SD (n = 10 in each group). *P < 0.05 versus the sham group, #P < 0.05 versus MI/R group.

Figure 6

Resveratrol ameliorates oxidative stress after myocardial ischemia/reperfusion injury. Resveratrol significantly decreased (A) the content of malondialdehyde (MDA) and (B) enhanced superoxide dismutase (SOD); and (C) glutathione peroxidase (GSH-PX) activities in ischemia reperfusion rats’ heart. Data were expressed as mean ± SD (n = 10 in each group). *P < 0.05 versus the sham group, #P < 0.05 versus MI/R group.

Figure 7

Western blot analysis for Nrf2 and HO-1 expression. A, B. Representative photographs of the Western blot show Nrf2 and HO-1 protein levels in sham, MI/R and MI/R + Res respectively. C, D. The graphs show that Nrf2 and HO-1, and protein levels were increased after MI/R and more significantly induced by treatment with resveratrol. Data were expressed as mean ± SD (n = 10 in each group). *P < 0.05 versus the sham group, #P < 0.05 versus MI/R group.