Effects of edaravone on the expression of β-defensin-2 mRNA in lung tissue of rats with myocardial ischemia reperfusion

Zhang,Weiwei; Guo,Yongqing; Yu,Shuzhen; Wei,Jianfeng; Jin,Jianmin

doi:10.3892/mmr.2013.1393

Effects of edaravone on the expression of β-defensin-2 mRNA in lung tissue of rats with myocardial ischemia reperfusion

Authors:
- Weiwei Zhang
- Yongqing Guo
- Shuzhen Yu
- Jianfeng Wei
- Jianmin Jin
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Affiliations: Department of Anesthesiology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, P.R. China
Published online on: March 22, 2013 https://doi.org/10.3892/mmr.2013.1393
Pages: 1683-1687

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Abstract

The aim of this study was to investigate the effects of edaravone on lung injury caused by myocardial ischemia reperfusion (I/R) in rats. Wistar rats (n=24) were randomly divided into 4 groups: the sham operation (S group) and myocardial I/R groups (C group) and two edaravone‑treated groups (E1 and E2 groups). Rats in the E1 and E2 groups were injected with 3 or 10 mg/kg edaravone, respectively, 1 min before reperfusion. The rats were sacrificed and the lung tissue, bronchoalveolar lavage (BAL) fluid and serum were obtained. The concentration of serum creatine kinase isoenzyme (CK-MB) was determined, the lung permeability index (PPI) was calculated and β-defensin-2 (BD-2) mRNA expression in the lung tissue and BD-2 and TNF-α protein content levels were determined. Serum CK-MB activity and the PPI were increased, while BD-2 mRNA and BD‑2 and TNF-α protein levels in the lung tissue were upregulated in the C, E1 and E2 groups compared with the S group. The above‑mentioned indicators were decreased in the E1 and E2 groups compared with the IR group. The level of the decrease for indicators in the E2 group was significantly different compared with that in the E1 group. In conclusion, edaravone reduced the lung injury caused by myocardial I/R in rats. Its mechanism of action was not only oxygen free radical scavenging, but was also associated with a suppression of the inflammatory response of the lung tissue.

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1	Murry CE, Jennings RB and Reimer KA: Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 74:1124–1136. 1986. View Article : Google Scholar
2	Mohan IK, Khan M, Wisel S, et al: Cardioprotection by HO-4038, a novel verapamil derivative, targeted against ischemia and reperfusion-mediated acute myocardial infarction. Am J Physiol Heart Circ Physiol. 296:H140–H151. 2009. View Article : Google Scholar
3	Kutala VK, Khan M, Mandal R, et al: Attenuation of myocardial ischemia-reperfusion injury by trimetazidine derivatives functionalized with antioxidant properties. J Pharmacol Exp Ther. 317:921–928. 2006. View Article : Google Scholar
4	Tang YH, Xu JJ, Li JX and Cheng XS: Remote postconditioning induced by brief pulmonary ischemia and reperfusion attenuates myocardial reperfusion injury in rabbits. Chin Med J (Engl). 124:1683–1688. 2011.
5	Kitashiro S, Sugiura T, Tamura T, et al: Factors associated with increased extravascular lung water in cardiac tamponade and myocardial ischemia. Crit Care Med. 27:2229–2233. 1999. View Article : Google Scholar : PubMed/NCBI
6	He X, Han B, Mura M, et al: Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice. PLoS One. 3:e15272008. View Article : Google Scholar
7	Faubel S: Pulmonary complications after acute kidney injury. Adv Chronic Kidney Dis. 15:284–296. 2008. View Article : Google Scholar : PubMed/NCBI
8	Andrés-Hernando A, Altmann C, Ahuja N, et al: Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice. Am J Physiol Renal Physiol. 301:F907–F916. 2011.PubMed/NCBI
9	Shu Q, Shi Z, Zhao Z, et al: Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of beta-defensin-2 in rats. Shock. 26:365–371. 2006.
10	Hu Q, Zuo P, Shao B, et al: Administration of nonviral gene vector encoding rat beta-defensin-2 ameliorates chronic Pseudomonas aeruginosa lung infection in rats. J Gene Med. 12:276–286. 2010.PubMed/NCBI
11	Wu QP, Yao SL and Fang XM: Study of rat beta-defensin-2 gene and protein expression in ventilator-associated pneumonia. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 17:353–356. 2005.(In Chinese).
12	Liu KX, Chen SQ, Zhang H, et al: Intestinal ischemia/reperfusion upregulates beta-defensin-2 expression and causes acute lung injury in the rat. Injury. 40:950–955. 2009. View Article : Google Scholar : PubMed/NCBI
13	Yamazaki K, Miwa S, Toyokuni S, et al: Effect of edaravone, a novel free radical scavenger, supplemented to cardioplegia on myocardial function after cardioplegic arrest: in vitro study of isolated rat heart. Heart Vessels. 24:228–235. 2009. View Article : Google Scholar
14	Liu N, Shang J, Tian F, et al: In vivo optical imaging for evaluating the efficacy of edaravone after transient cerebral ischemia in mice. Brain Res. 1397:66–75. 2011. View Article : Google Scholar : PubMed/NCBI
15	Shimoda M, Iwasaki Y, Okada T, et al: Edaravone inhibits apoptosis caused by ischemia/reperfusion injury in a porcine hepatectomy model. World J Gastroenterol. 18:3520–3526. 2012. View Article : Google Scholar : PubMed/NCBI
16	Salvi S: Protecting the myocardium from ischemic injury: a critical role for alpha(1)-adrenoreceptors? Chest. 119:1242–1249. 2001. View Article : Google Scholar : PubMed/NCBI
17	Waisman D, Brod V, Dickstein R, et al: Effects of inhaled nitric oxide on lung injury after intestinal ischemia-reperfusion in rats. Shock. 23:150–155. 2005. View Article : Google Scholar : PubMed/NCBI
18	Chung WO and Dale BA: Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species. Infect Immun. 72:352–358. 2004. View Article : Google Scholar
19	van Wetering S, Sterk PJ, Rabe KF and Hiemstra PS: Defensins: key players or bystanders in infection, injury, and repair in the lung? J Allergy Clin Immunol. 104:1131–1138. 1999.PubMed/NCBI
20	Pace E, Ferraro M, Minervini MI, et al: Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients. PLoS One. 7:e336012012. View Article : Google Scholar : PubMed/NCBI
21	Onder A, Kapan M, Gümüş M, et al: The protective effects of curcumin on intestine and remote organs against mesenteric ischemia/reperfusion injury. Turk J Gastroenterol. 23:141–147. 2012.PubMed/NCBI
22	Steubesand N, Kiehne K, Brunke G, et al: The expression of the beta-defensins hBD-2 and hBD-3 is differentially regulated by NF-kappaB and MAPK/AP-1 pathways in an in vitro model of Candida esophagitis. BMC Immunol. 10:362009. View Article : Google Scholar : PubMed/NCBI
23	Yamawaki M, Sasaki N, Shimoyama M, et al: Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit cardiomyocytes. Br J Pharmacol. 142:618–626. 2004. View Article : Google Scholar : PubMed/NCBI
24	Wu TW, Zeng LH, Wu J and Fung KP: Myocardial protection of MCI-186 in rabbit ischemia-reperfusion. Life Sci. 71:2249–2255. 2002. View Article : Google Scholar : PubMed/NCBI
25	Reyes YA, Shimoyama T, Akamatsu H and Sunamori M: MCI-186 (edaravone), a free radical scavenger, attenuates ischemia-reperfusion injury and activation of phospholipase A(2) in an isolated rat lung model after 18 h of cold preservation. Eur J Cardiothorac Surg. 29:304–311. 2006. View Article : Google Scholar
26	Asai T, Ohno Y, Minatoguchi S, et al: The specific free radical scavenger edaravone suppresses bleomycin-induced acute pulmonary injury in rabbits. Clin Exp Pharmacol Physiol. 34:22–26. 2007. View Article : Google Scholar : PubMed/NCBI
27	Xu JZ, Shen BZ, Li Y, et al: Edaravone attenuates ischemia-reperfusion injury by inhibiting oxidative stress in a canine lung transplantation model. Chin Med J (Engl). 121:1583–1587. 2008.PubMed/NCBI
28	Yang T, Mao YF, Liu SQ, et al: Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury. Eur J Pharmacol. 630:152–157. 2010. View Article : Google Scholar : PubMed/NCBI
29	Nakamura T, Kuroda Y, Yamashita S, et al: Edaravone attenuates brain edama and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke. 39:463–469. 2008. View Article : Google Scholar : PubMed/NCBI
30	Miyasou T, Kwon AH, Tsuji K, et al: Edaravone prevents Fas-induced fulminant hepatic failure in mice by regulating mitochondrial Bcl-xL and Bax. Shock. 30:212–216. 2008.PubMed/NCBI
31	Yuan WJ, Yasuhara T, Shingo T, et al: Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons. BMC Neurosci. 9:752008. View Article : Google Scholar : PubMed/NCBI