Resveratrol up regulates the expression of SIRT1 and mediates protective effect on radiation-induced myocardial injury
Xu Yilin, Chen Yanxin, Cai Yini, Xu Peng, Zeng Zhimin, Huang Long, Liu Anwen
Department of Oncology, the Second Affiliated Hospital of Nanchang University, Jiangxi Key Laboratory of Clinical Translational Cancer Research, Radiation Induced Heart Damage Institute of Nanchang University, Nanchang 330006, China
Abstract：Objective To evaluate the effect of resveratrol on radiation-induced myocardial injury in mice. Methods A total of 80 C57BL/6 mice were randomly divided into the control group, resveratrol (Res) group, radiation (RT) group and radiation+resveratrol (RT+Res) group. In the RT group, mice were given with heart radiation and mice in the Res group were given with resveratrol by gavage for 3 months. Cardiac ultrasound was used to evaluate cardiac function at 3 months after cardiac radiation. The hearts of mice were collected for HE staining, immunofluorescence, TUNEL staining, Masson staining and Western blot to evaluate the expression of silent information regulator 1 (SIRT1), the level of oxidative stress, inflammatory response, apoptosis and the degree of fibrosis in myocardial tissues. Experimental data were expressed as Mean ± SD. Continous data were statistically analyzed by t-test. Results After 3 months of irradiation, compared with the control group, the ejection fraction (EF) and fractional shortening (FS) of cardiac function were decreased, and myocardial degeneration and disorder, reactive oxygen species (ROS) and inflammatory levels (interleukin-1β, interleukin-6, tumor necrosis factor-α), myocardial apoptosis (TUNEL positive cell rate) and fibrosis were increased in the RT group. In the RT+Res group, the cardiac function was improved, the expression of SIRT1 was increased, and the levels of oxidative stress, inflammation, myocardial apoptosis and fibrosis were decreased. Conclusions Resveratrol can reduce oxidative stress, inflammatory infiltration, apoptosis and fibrosis of myocardium in mice with radiation-induced myocardial injury, thereby improving cardiac structural abnormalities and cardiac dysfunction. This protective effect can be mediated by upregulation of SIRT1 expression.
Xu Yilin,Chen Yanxin,Cai Yini et al. Resveratrol up regulates the expression of SIRT1 and mediates protective effect on radiation-induced myocardial injury[J]. Chinese Journal of Radiation Oncology, 2023, 32(5): 457-463.
[1] Meattini I, Poortmans PM, Aznar MC, et al.Association of breast cancer irradiation with cardiac toxic effects: a narrative review[J]. JAMA Oncol, 2021,7(6):924-932. DOI: 10.1001/jamaoncol.2020.7468. [2] Desai MY, Windecker S, Lancellotti P, et al.Prevention, diagnosis, and management of radiation-associated cardiac disease: JACC scientific expert panel[J]. J Am Coll Cardiol, 2019,74(7):905-927. DOI: 10.1016/j.jacc.2019.07.006. [3] Ping Z, Peng Y, Lang H, et al.Oxidative stress in radiation-induced cardiotoxicity[J]. Oxid Med Cell Longev, 2020,2020:3579143. DOI: 10.1155/2020/3579143. [4] Singh AP, Singh R, Verma SS, et al.Health benefits of resveratrol: evidence from clinical studies[J]. Med Res Rev, 2019,39(5):1851-1891. DOI: 10.1002/med.21565. [5] Cheng CK, Luo JY, Lau CW, et al.Pharmacological basis and new insights of resveratrol action in the cardiovascular system[J]. Br J Pharmacol, 2020,177(6):1258-1277. DOI: 10.1111/bph.14801. [6] D'Onofrio N, Servillo L, Balestrieri ML. SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection[J]. Antioxid Redox Signal, 2018,28(8):711-732. DOI: 10.1089/ars.2017.7178. [7] Chang HC, Guarente L.SIRT1 and other sirtuins in metabolism[J]. Trends Endocrinol Metab, 2014,25(3):138-145. DOI: 10.1016/j.tem.2013.12.001. [8] Luo GP, Jian Z, Zhu Y, et al.Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress[J]. Int J Mol Med, 2019,43(5):2033-2043. DOI: 10.3892/ijmm.2019.4125. [9] Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer[J]. N Engl J Med, 2013,368(11):987-998. DOI: 10.1056/NEJMoa1209825. [10] Barjaktarovic Z, Schmaltz D, Shyla A, et al.Radiation-induced signaling results in mitochondrial impairment in mouse heart at 4 weeks after exposure to X-rays[J]. PLoS One, 2011,6(12):e27811. DOI: 10.1371/journal.pone.0027811. [11] Sun ZM, Guan P, Luo LF, et al.Resveratrol protects against CIH-induced myocardial injury by targeting Nrf2 and blocking NLRP3 inflammasome activation[J]. Life Sci, 2020,245:117362. DOI: 10.1016/j.lfs.2020.117362. [12] Shen M, Jia GL, Wang YM, et al.Cardioprotective effect of resvaratrol pretreatment on myocardial ischemia- reperfusion induced injury in rats[J]. Vascul Pharmacol, 2006,45(2):122-126. DOI: 10.1016/j.vph.2006.04.002. [13] Zou LX, Chen C, Yan X, et al.Resveratrol attenuates pressure overload-induced cardiac fibrosis and diastolic dysfunction via PTEN/AKT/Smad2/3 and NF-κB signaling pathways[J]. Mol Nutr Food Res, 2019,63(24):e1900418. DOI: 10.1002/mnfr.201900418. [14] Gao PY, Li N, Ji KH, et al.Resveratrol targets TyrRS acetylation to protect against radiation-induced damage[J]. FASEB J, 2019,33(7):8083-8093. DOI: 10.1096/fj.201802474RR. [15] Radwan RR, Karam HM.Resveratrol attenuates intestinal injury in irradiated rats via PI3K/Akt/mTOR signaling pathway[J]. Environ Toxicol, 2020,35(2):223-230. DOI: 10.1002/tox.22859. [16] Xia N, Daiber A, Förstermann U, et al.Antioxidant effects of resveratrol in the cardiovascular system[J]. Br J Pharmacol, 2017,174(12):1633-1646. DOI: 10.1111/bph.13492. [17] Meng TT, Xiao DF, Muhammed A, et al.Anti-inflammatory action and mechanisms of resveratrol[J]. Molecules, 2021,26(1):229. DOI: 10.3390/molecules26010229. [18] Bonnefont-Rousselot D.Resveratrol and cardiovascular diseases[J]. Nutrients, 2016,8(5):250. DOI: 10.3390/nu8050250. [19] Dai H, Sinclair DA, Ellis JL, et al.Sirtuin activators and inhibitors: promises, achievements, and challenges[J]. Pharmacol Ther, 2018,188:140-154. DOI: 10.1016/j.pharmthera.2018.03.004. [20] Cao DF, Wang MZ, Qiu XY, et al.Structural basis for allosteric, substrate-dependent stimulation of SIRT1 activity by resveratrol[J]. Genes Dev, 2015,29(12):1316-1325. DOI: 10.1101/gad.265462.115. [21] Hou XB, Rooklin D, Fang H, et al.Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation[J]. Sci Rep, 2016,6:38186. DOI: 10.1038/srep38186. [22] Zhang QJ, Wang Z, Chen HZ, et al.Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice[J]. Cardiovasc Res, 2008,80(2):191-199. DOI: 10.1093/cvr/cvn224. [23] Bao XC, Wang Y, Li X, et al.Identification of 'erasers' for lysine crotonylated histone marks using a chemical proteomics approach[J]. Elife, 2014,3:e02999. DOI: 10.7554/eLife.02999. [24] Hsu CP, Zhai P, Yamamoto T, et al.Silent information regulator 1 protects the heart from ischemia/reperfusion[J]. Circulation, 2010,122(21):2170-2182. DOI: 10.1161/CIRCULATIONAHA.110.958033. [25] Prola A, Pires Da Silva J, Guilbert A, et al. SIRT1 protects the heart from ER stress-induced cell death through eIF2α deacetylation[J]. Cell Death Differ, 2017,24(2):343-356. DOI: 10.1038/cdd.2016.138. [26] Novelle MG, Wahl D, Diéguez C, et al.Resveratrol supplementation: where are we now and where should we go?[J]. Ageing Res Rev, 2015,21:1-15. DOI: 10.1016/j.arr.2015.01.002.
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