Resveratrol alleviates hypoxia/reoxygenation injury‑induced mitochondrial oxidative stress in cardiomyocytes

Li,Tao; Chen,Linlin; Yu,Yiyan; Yang,Binbin; Li,Pengyun; Tan,Xiao‑Qiu

doi:10.3892/mmr.2019.9943

Resveratrol alleviates hypoxia/reoxygenation injury‑induced mitochondrial oxidative stress in cardiomyocytes

Authors:
- Tao Li
- Linlin Chen
- Yiyan Yu
- Binbin Yang
- Pengyun Li
- Xiao‑Qiu Tan
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Affiliations: Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: February 7, 2019 https://doi.org/10.3892/mmr.2019.9943
Pages: 2774-2780
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Resveratrol (RES) is a naturally occurring antioxidant compound found in red wine. Although it has been demonstrated to have a cardioprotective effect, the mechanism underlying this effect remains to be fully elucidated. The aim of the present study was to determine whether RES exerts a protective effect against mitochondrial oxidative stress and apoptosis in neonatal rat cardiomyocytes (NRCMs) induced by hypoxia/reoxygenation (H/R) injury. Primary cultured NRCMs were used as a model system and were divided into four experimental groups: Control, H/R, H/R + DMSO (H/R with 0.2% DMSO) and H/R + RES (H/R with 100 µM RES) groups. Mitochondrial oxidative stress was determined by measuring the alteration in the mitochondrial membrane potential (ΔΨm) of NRCMs, the release of lactate dehydrogenase (LDH) and the ratio of B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein (Bax) from NRCMs. Cell apoptosis was assessed by measuring cell apoptotic rates and the activity of caspase 3. In the H/R+RES group, RES significantly alleviated structural impairment, including disordered α‑actin and F‑actin, in the NRCMs induced by H/R injury. RES attenuated H/R injury‑induced mitochondria oxidative stress. RES also attenuated H/R injury‑induced cell apoptosis; it decreased the NRCM apoptotic rate from 84.25±7.41% (H/R) to 46.39±5.43% (H/R+RES) (P<0.05, n=4), rescued the decrease in the Bcl2/Bax ratio induced by H/R from 0.53±0.08‑fold (H/R) to 0.86±0.06‑fold (H/R+RES) (P<0.05, n=5) and alleviated the increased activity of caspase 3 induced by H/R from 1.32±0.06‑fold to 1.02±0.04‑fold (P<0.05, n=5). Furthermore, RES significantly attenuated the increment of LDH release induced by H/R injury in NRCMs from 1.41±0.03‑fold (H/R) to 1.02±0.06‑fold (H/R+RES) (P<0.01, n=4) and alleviated the depolarization of ΔΨm induced by H/R, shifting the ratio of JC‑1 monomer from 62.39±1.82% (H/R) to 35.31±8.63% (H/R+RES) (P<0.05, n=4). RES alleviated the decrease in sirtuin 1 induced by H/R injury from 0.61±0.06‑fold (H/R) to 1.01±0.05‑fold (H/R+RES) (P<0.05, n=5). In conclusion, the present study is the first, to the best of our knowledge, to demonstrate that RES provides cardioprotection against H/R injury through decreasing mitochondria‑mediated oxidative stress injury and structural impairment in NRCMs. These results provide scientific evidence for the clinical application of RES in the treatment of cardiac conditions.

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