Resveratrol attenuates the inflammatory reaction induced by ischemia/reperfusion in the rat heart

Cong,Xiaoqiang; Li,Ying; Lu,Na; Dai,Yajian; Zhang,Huijie; Zhao,Xin; Liu,Ya

doi:10.3892/mmr.2014.2090

Resveratrol attenuates the inflammatory reaction induced by ischemia/reperfusion in the rat heart

Authors:
- Xiaoqiang Cong
- Ying Li
- Na Lu
- Yajian Dai
- Huijie Zhang
- Xin Zhao
- Ya Liu
View Affiliations

Affiliations: Department of Cardiology, Bethune First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Emergency Internal Medicine, The People's Hospital of Jilin Province, Changchun, Jilin 130021, P.R. China, Department of Internal Medicine, The Friendship Hospital of Linjiang, Linjiang, Jilin 134600, P.R. China, Department of Nutrition and Toxicology, School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: March 28, 2014 https://doi.org/10.3892/mmr.2014.2090
Pages: 2528-2532

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The role of resveratrol (Res) in inflammation induced by ischemia/reperfusion is not well understood. The aim of the present study was to investigate whether Res modulates neutrophil accumulation and tumor necrosis factor‑α (TNF‑α) induction in an ischemia/reperfusion‑injured rat heart model. The rats were randomly exposed to sham surgery, myocardial ischemia/reperfusion (MI/R) alone, MI/R + Res, MI/R + Res + L‑NG‑nitroarginine methyl ester (L‑NAME) and MI/R + Res + methylene blue (MB). The results demonstrated that compared with MI/R, Res reduced the myocardial infarct area, myocardial myeloperoxidase levels, serum creatinine kinase and lactate dehydrogenase levels, and serum and myocardial TNF‑α production. All the effects of Res demonstrated were inhibited by L‑NAME (a nitric oxide (NO) synthase inhibitor) and MB [a cyclic guanosine monophosphate (cGMP) inhibitor]. Thus, Res produces cardioprotective and anti‑inflammatory effects. These effects may be associated with an increase in NO production, the inhibition of neutrophil accumulation, TNF‑α induction and cGMP signaling pathways in myocardium subjected to MI/R.

View Figures

View References

1	Xiong J, Xue FS, Yuan YJ, Wang Q, Liao X and Wang WL: Cholinergic anti-inflammatory pathway: a possible approach to protect against myocardial ischemia reperfusion injury. Chin Med J (Engl). 123:2720–2726. 2010.PubMed/NCBI
2	Naidu BV, Farivar AS, Woolley SM, et al: Novel broad-spectrum chemokine inhibitor protects against lung ischemia-reperfusion injury. J Heart Lung Transplant. 23:128–134. 2004. View Article : Google Scholar : PubMed/NCBI
3	Renaud S and de Lorgeril M: Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet. 339:1523–1526. 1992. View Article : Google Scholar : PubMed/NCBI
4	Athar M, Back JH, Tang X, et al: Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol. 224:274–283. 2007. View Article : Google Scholar : PubMed/NCBI
5	Aluyen JK, Ton QN, Tran T, et al: Resveratrol: potential as anticancer agent. J Diet Suppl. 9:45–56. 2012. View Article : Google Scholar : PubMed/NCBI
6	Piotrowska H, Myszkowski K, Zio’łkowska A, et al: Resveratrol analogue 3,4,4′,5-tetramethoxystilbene inhibits growth, arrests cell cycle and induces apoptosis in ovarian SKOV-3 and A-2780 cancer cells. Toxicol Appl Pharmacol. 263:53–60. 2012.
7	Afaq F, Adhami VM and Ahmad N: Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice. Toxicol Appl Pharmacol. 186:28–37. 2003.PubMed/NCBI
8	Sehirli O, Sakarcan A, Velioğlu-Oğünç A, et al: Resveratrol improves ifosfamide-induced Fanconi syndrome in rats. Toxicol Appl Pharmacol. 222:33–41. 2007. View Article : Google Scholar : PubMed/NCBI
9	Xu Y, Nie L, Yin YG, et al: Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells. Toxicol Appl Pharmacol. 259:395–401. 2012. View Article : Google Scholar : PubMed/NCBI
10	Li F, Gong Q, Dong H and Shi J: Resveratrol, a neuroprotective supplement for Alzheimer’s disease. Curr Pharm Des. 18:27–33. 2012.
11	López-Miranda V, Soto-Montenegro ML, Vera G, et al: Resveratrol: a neuroprotective polyphenol in the Mediterranean diet. Rev Neurol. 54:349–356. 2012.(In Spanish).
12	Lanzilli G, Cottarelli A, Nicotera G, et al: Anti-inflammatory effect of resveratrol and polydatin by in vitro IL-17 modulation. Inflammation. 35:240–248. 2012. View Article : Google Scholar : PubMed/NCBI
13	Black SC and Rodger IW: Methods for studying experimental myocardial ischemic and reperfusion injury. J Pharmacol Toxicol Methods. 35:179–190. 1996. View Article : Google Scholar : PubMed/NCBI
14	Speyer CL and Ward PA: Role of endothelial chemokines and their receptors during inflammation. J Invest Surg. 24:18–27. 2011. View Article : Google Scholar : PubMed/NCBI
15	Khimenko PL, Bagby GJ, Fuseler J and Taylor AE: Tumor necrosis factor-alpha in ischemia and reperfusion injury in rat lungs. J Appl Physiol (1985). 85:2005–2011. 1998.PubMed/NCBI
16	Batista ML Jr, Rosa JC, Lopes RD, et al: Exercise training changes IL-10/TNF-alpha ratio in the skeletal muscle of post-MI rats. Cytokine. 49:102–108. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhu J, Liu M, Kennedy RH and Liu SJ: TNF-alpha-induced impairment of mitochondrial integrity and apoptosis mediated by caspase-8 in adult ventricular myocytes. Cytokine. 34:96–105. 2006. View Article : Google Scholar : PubMed/NCBI
18	Meldrum DR, Cleveland JC Jr, Cain BS, Meng X and Harken AH: Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Ann Thorac Surg. 65:439–443. 1998. View Article : Google Scholar
19	Gurevitch J, Frolkis I, Yuhas Y, et al: Antitumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion. J Am Coll Cardiol. 30:1554–1561. 1997. View Article : Google Scholar : PubMed/NCBI
20	Lefer AM, Ma XL, Weyrich A and Lefer DJ: Endothelial dysfunction and neutrophil adherence as critical events in the development of reperfusion injury. Agents Actions Suppl. 41:127–135. 1993.PubMed/NCBI
21	Schwartz BG and Kloner RA: Coronary no reflow. J Mol Cell Cardiol. 52:873–882. 2012. View Article : Google Scholar
22	Ma XL, Lefer DJ, Lefer AM and Rothlein R: Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesion molecule-1 in myocardial ischemia and reperfusion. Circulation. 86:937–946. 1992. View Article : Google Scholar : PubMed/NCBI
23	Chandrasekar B, Smith JB and Freeman GL: Ischemia-reperfusion of rat myocardium activates nuclear factor-kappaB and induces neutrophil infiltration via lipopolysaccharide-induced CXC chemokine. Circulation. 103:2296–2302. 2001. View Article : Google Scholar
24	Liu P, Hock CE, Nagele R and Wong PY: Formation of nitric oxide, superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury in rats. Am J Physiol. 272:H2327–H2336. 1997.PubMed/NCBI
25	Li J, Wu F, Zhang H, et al: Insulin inhibits leukocyte-endothelium adherence via an Akt-NO-dependent mechanism in myocardial ischemia/reperfusion. J Mol Cell Cardiol. 47:512–519. 2009. View Article : Google Scholar : PubMed/NCBI
26	Li J, Zhang H, Wu F, et al: Insulin inhibits tumor necrosis factor-alpha induction in myocardial ischemia/reperfusion: role of Akt and endothelial nitric oxide synthase phosphorylation. Crit Care Med. 36:1551–1558. 2008. View Article : Google Scholar
27	Alcendor RR, Gao S, Zhai P, et al: Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 100:1512–1521. 2007. View Article : Google Scholar : PubMed/NCBI
28	Danz ED, Skramsted J, Henry N, Bennett JA and Keller RS: Resveratrol prevents doxorubicin cardiotoxicity through mitochondrial stabilization and the Sirt1 pathway. Free Radic Biol Med. 46:1589–1597. 2009. View Article : Google Scholar : PubMed/NCBI
29	Pillai JB, Isbatan A, Imai S and Gupta MP: Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD⁺ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem. 280:43121–43130. 2005. View Article : Google Scholar : PubMed/NCBI
30	Wallerath T, Li H, Godtel-Ambrust U, Schwarz PM and Forstermann U: Blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide. 12:97–104. 2005. View Article : Google Scholar : PubMed/NCBI
31	Penumathsa SV, Thirunavukkarasu M, Koneru S, et al: Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat. J Mol Cell Cardiol. 42:508–516. 2007. View Article : Google Scholar : PubMed/NCBI
32	Rush JW, Quadrilatero J, Levy AS and Ford RJ: Chronic resveratrol enhances endothelium-dependent relaxation but does not alter eNOS levels in aorta of spontaneously hypertensive rats. Exp Biol Med (Maywood). 232:814–822. 2007.PubMed/NCBI
33	Beher D, Wu J, Cumine S, et al: Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des. 74:619–624. 2009. View Article : Google Scholar : PubMed/NCBI
34	Chakrabarty SP, Balaram H and Chandrasekaran S: Sirtuins: multifaceted drug targets. Curr Mol Med. 11:709–718. 2011. View Article : Google Scholar : PubMed/NCBI