Resveratrol as a Promising Polyphenol in Age-Associated Cardiac Alterations

Abstract

According to a widely accepted theory, oxidative stress is considered to be the number one trigger of aging-associated degenerative processes including cardiovascular diseases. In the context of aging-research, resveratrol receives special attention with its surprising number of health benefits. The aim of our study was to examine the anti-inflammatory and antioxidant effects of this dietary polyphenol in aging rat heart. 20-month-old female and male Wistar rats were divided into control (untreated) and resveratrol-treated groups. Resveratrol was administered at a dose of 0.05 mg/ml for 12 weeks dissolved in drinking water, while the control rats received ad libitum water. Cardiac level of reactive oxygen species (ROS), nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNF-α), and glutathione (GSH) parameters, as well as the activity of myeloperoxidase (MPO) and heme oxygenase (HO) enzymes were detected. Together with the biochemical measurements, hearts were isolated and used for an exposure of ischemic-reperfusion injury via Langendorff perfusion system. 12 week of resveratrol treatment suppressed the age-related inflammatory pathways including the expression of TNF-α, NFκB, and the activity of MPO while intensified the endogenous antioxidant defenses through the induction of GSH and HO system. Presumably, as a result of these processes, the necrotic area of the heart in response to an acute injury was also significantly reduced in the resveratrol-treated groups. Our findings confirmed that resveratrol has cardioprotective effects at several points by counteracting the aging-associated cellular malfunctions in the heart.

Figure 1

The effects of a 12-week-long resveratrol treatment on the magnitude of the infarct size in aged rats. Infarct size (IS) was calculated as the percentage of the area at risk (AAR). One-way ANOVA and Tukey posttest result is shown as mean ± SD; n = 8 − 9/group, ^∗∗p < 0.01, and ^∗∗∗∗p < 0.0001. Statistical significance between resveratrol-treated and nontreated control counterparts. RESV: Resveratrol; IS: Infarct size; AAR: Area at risk.

Figure 2

(a) The effects of a 12-week-long resveratrol treatment on cardiac NFκB concentration in aged rats (NFκB; expressed as pg/mg protein). One-way ANOVA and Tukey posttest result is shown as mean ± SD; n = 7 − 8/group. (b) The effects of a 12-week-long resveratrol treatment on cardiac TNF-α expression in aged rats (TNF-α; expressed as pg/mg protein). One-way ANOVA and Tukey posttest result is shown as mean ± SD; n = 6 − 8/group. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, and ^∗∗∗∗p < 0.0001: Statistical significance between resveratrol-treated and nontreated control counterparts. RESV: Resveratrol; NFκB: Nuclear factor kappa B; TNF-α: Tumor necrosis factor alpha.

Figure 3

The effects of a 12-week-long resveratrol treatment on cardiac myeloperoxidase enzyme activity in aged rats (MPO; expressed as μU/mg protein). Non-Gaussian distribution and Kruskal-Wallis test with Dunn's post hoc test result is shown as mean ± SD; n = 7 − 8/group. ^∗∗∗p < 0.001: Statistical significance between resveratrol-treated and nontreated control counterparts. RESV: Resveratrol; MPO: Myeloperoxidase.

Figure 4

The effects of a 12-week-long resveratrol treatment on cardiac reactive oxygen species in aged rats (ROS; expressed as U/mg protein). Non-Gaussian distribution and Kruskal-Wallis test with Dunn's post hoc test result is shown as mean ± SD; n = 7 − 9/group and ^∗p < 0.05: Statistical significance between resveratrol-treated and nontreated control counterparts. RESV: Resveratrol; ROS: Reactive oxygen species.

Figure 5

The effects of a 12-week-long resveratrol treatment on cardiac GSH+GSSG content in aged rats (GSH+GSSG; expressed as nmol/mg protein). Non-Gaussian distribution and Kruskal-Wallis test with Dunn's post hoc test result is shown as mean ± SD; n = 7 − 9/group and ^∗∗p < 0.01: Statistical significance between resveratrol-treated and nontreated control counterparts. RESV: Resveratrol; GSH+GGSG: Total glutathione.

Figure 6

The effects of a 12-week-long resveratrol treatment on cardiac HO activity in aged rats (HO activity; expressed as nmol/bilirubin/h/mg protein). One-way ANOVA and Tukey posttest result is shown as mean ± SD; n = 7 − 8/group, ^∗∗p < 0.01, and ^∗∗∗∗p < 0.0001: Statistical significance between resveratrol-treated and nontreated control counterparts. RESV: Resveratrol; HO: Heme oxygenase.

Figure 7

Summary of the study. Resveratrol sufficiently suppressed the age-related inflammatory pathways including the expression of TNF-α, NFκB, and the activity of MPO while intensified the endogenous antioxidant defenses through the induction of GSH and HO system. Presumably, as a result of these processes, the necrotic extension of the heart was also significantly reduced. HO: Heme oxygenase; GSH+GGSG: Total glutathione; ROS: Reactive oxygen species; NFκB: Nuclear factor kappa B; TNF-α: Tumor necrosis factor alpha; MPO: Myeloperoxidase enzyme.