Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Attenuation of Cardiac Ischaemia-reperfusion Injury by Treatment with Hydrogen-rich Water

Author(s): Xiangzi Li, Liangtong Li, Xuanchen Liu, Jiawen Wu, Xiaoyu Sun, Zhilin Li, Yong-Jian Geng, Fulin Liu* and Yujuan Zhou*

Volume 19, Issue 4, 2019

Page: [294 - 302] Pages: 9

DOI: 10.2174/1566524019666190321113544

open access plus

Abstract

Background: Hydrogen has been shown to exert a bioactive effect on the myocardium. This study examined the signalling pathways for hydrogen attenuating ischaemia-reperfusion injury.

Methods: In total, 20 male Wistar rats were evaluated for the effects of hydrogen-rich water on ischaemia-reperfusion in hearts. Left ventricular tissue was taken for screening and analysis of active protein factors by protein chip technology. The enrichment of the KEGG pathway was obtained by using the Gene Ontology (GO) enrichment principle. The expression of JAK2, STAT1, STAT3, p-STAT1, p-JAK2, p-STAT3 in rat myocardium was detected by Western blot analysis and immunohistochemistry. The apoptosis rates of the control and hydrogen-rich water groups were detected by TUNEL staining.

Results: The expression levels of 25 proteins, including five transduction pathways, were downregulated in the hydrogen-rich water group. The expression levels of p- JAK2/JAK2, p-STAT3/STAT3 were upregulated in the hydrogen-rich water group compared with the control group, and p-STAT1/STAT1 was downregulated in the hydrogen-rich water group compared with the control group. Furthermore, the apoptosis rate was significantly decreased in the hydrogen-rich water group, as well.

Conclusion: Hydrogen-rich water may inhibit the apoptosis of cardiomyocytes after ischaemia-reperfusion by upregulating the expression of the JAK2-STAT3 signalling pathway, which reduces ischaemia-reperfusion injury.

Keywords: Hydrogen-rich water, ischaemia-reperfusion injury, JAK-STAT signalling pathway, protein chip technique, apoptosis.

[1]
Sanderson TH, Reynolds CA, Kumar R, Przyklenk K, Huttemann M. Molecular mechanisms of ischemia-reperfusion injury in brain: pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol 2013; 47: 9-23.
[2]
Lesnefsky EJ, Chen Q, Tandler B, Hoppel CL. Mitochondrial dysfunction and myocardial ischemia-reperfusion: implications for novel therapies. Annu Rev Pharmacol Toxicol 2017; 57: 535-65.
[3]
Ghavami S, Gupta S, Ambrose E, et al. Autophagy and heart disease: implications for cardiac ischemia-reperfusion damage. Curr Mol Med 2014; 14(5): 616-29.
[4]
Xin L, Junhua W, Long L, et al. Exogenous Hydrogen Sulfide Protects SH-SY5Y Cells from OGD/R-Induced Injury. Curr Mol Med 2017; 17(8): 563-7.
[5]
Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res 2010; 44(9): 971-82.
[6]
Zhang Y, Sun Q, He B, Xiao J, Wang Z, Sun X. Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion. Int J Cardiol 201(148): 91-5.
[7]
Yu S, Zhao C, Che N, Jing L, Ge R. Hydrogen-rich saline attenuates eosinophil activation in a guinea pig model of allergic rhinitis via reducing oxidative stress. J Inflamm 2017; 14: 1.
[8]
Sun Q, Kang Z, Cai J, et al. Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats. Exp Biol Med (Maywood) 2009; 234: 1212-9.
[9]
Liu Xuecong, Liu Fulin, Li Zhilin, Zhou Xiaodong, Shen Wenzeng, Zhou Cheng Protective effect and mechanism of hydrogen on isolated myocardial ischemia-reperfusion injury in rats. Shandong Medicine 2015; 55(6): 1-3.
[10]
Berrade L, Garcia AE, Camarero JA. Protein microarrays: novel developments and applications. Pharm Res 2011; 28: 1480-99.
[11]
Zarco N, Gonzalez-Ramirez R, Gonzalez RO, Segovia J. GAS1 induces cell death through an intrinsic apoptotic pathway. Apoptosis 2012; 17: 627-35.
[12]
Waskow C, Liu K, Darrasse-Jeze G, et al. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat Immunol 2008; 9: 676-83.
[13]
Laouar Y, Welte T, Fu XY, Flavell RA. STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity 2003; 19: 903-12.
[14]
Segura E, Touzot M, Bohineust A, et al. Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity 2013; 38: 336-48.
[15]
Liang SC, Tan XY, Luxenberg DP, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 2006; 203: 2271-9.
[16]
Chang SH, Dong C. IL-17F: regulation, signaling and function in inflammation. Cytokine 2009; 46: 7-11.
[17]
Yang XO, Chang SH, Park H, et al. Regulation of inflammatory responses by IL-17F. J Exp Med 2008; 205: 1063-75.
[18]
Sundblad V, Morosi LG, Geffner JR, Rabinovich GA. Galectin-1: a Jack-of-all-trades in the resolution of acute and chronic inflammation. J Immunol 2017; 199: 3721-30.
[19]
Weinmann D, André S, Walzer SM, et al. Galectin-1 induces inflammation and cartilage degeneration in osteoarthritis through NF-κB-signaling. Osteoarthritis Cartilage 2016; 24: S139-S40.
[20]
Seropian IM, Cerliani JP, Toldo S, et al. Galectin-1 controls cardiac inflammation and ventricular remodeling during acute myocardial infarction. Am J Pathol 2013; 182: 29-40.
[21]
Corada M, Chimenti S, Cera MR, et al. Junctional adhesion molecule-A-deficient polymorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia-reperfusion injury. Proc Natl Acad Sci USA 2005; 102: 10634-9.
[22]
Khandoga A, Kessler JS, Meissner H, et al. Junctional adhesion molecule-A deficiency increases hepatic ischemia-reperfusion injury despite reduction of neutrophil transendothelial migration. Blood 2005; 106: 725-33.
[23]
Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 2004; 9: 667-76.
[24]
Dimitrova V, Arcaro A. Targeting the PI3K/AKT/mTOR signaling pathway in medulloblastoma. Curr Mol Med 2015; 15(1): 82-93.
[25]
Wu H, Ye M, Yang J, et al. Nicorandil protects the heart from ischemia/reperfusion injury by attenuating endoplasmic reticulum response-induced apoptosis through PI3K/Akt signaling pathway. Cell Physiol Biochem 2015; 35: 2320-32.
[26]
Zhang J, Wang C, Yu S, et al. Sevoflurane postconditioning protects rat hearts against ischemia-reperfusion injury via the activation of PI3K/AKT/mTOR signaling. Sci Rep 2014; 4: 7317.
[27]
Wu J, Wang R, Yang D, et al. Hydrogen postconditioning promotes survival of rat retinal ganglion cells against ischemia/reperfusion injury through the PI3K/Akt pathway. Biochem Biophys Res Commun 2018; 495: 2462-8.
[28]
Zhu J, Yao K, Guo J, et al. miR-181a and miR-150 regulate dendritic cell immune inflammatory responses and cardiomyocyte apoptosis via targeting JAK1-STAT1/c-Fos pathway. J Cell Mol Med 2017; 21: 2884-95.
[29]
Liu H, Xie X, Yang X, Li Y, Wang Y, Xu D. Enhanced inflammatory damage by microRNA-136 targeting Klotho expression in HK-2 cells by modulating JAK/STAT pathway. Pharmazie 2017; 72: 265-71.
[30]
Jere SW, Abrahamse H, Houreld NN. The JAK/STAT signaling pathway and photobiomodulation in chronic wound healing. Cytokine Growth Factor Rev 2017; 38: 73-9.
[31]
Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci 2004; 117: 1281-3.
[32]
Heim MH. The Jak-STAT pathway: cytokine signalling from the receptor to the nucleus. J Recept Signal Transduct Res 1999; 19: 75-120.
[33]
Mudaliar H, Rayner B, Billah M, et al. Remote ischemic preconditioning attenuates EGR-1 expression following myocardial ischemia reperfusion injury through activation of the JAK-STAT pathway. Int J Cardiol 2017; 228: 729-41.
[34]
Wang Y, Wang D, Zhang L, Ye F, Li M, Wen K. Role of JAK-STAT pathway in reducing cardiomyocytes hypoxia/ reoxygenation injury induced by S1P postconditioning. Eur J Pharmacol 2016; 784: 129-36.
[35]
Knight RA, Scarabelli TM, and Stephanou A. STAT transcription in the ischemic heart. JAK-STAT 2012; 1: 111-7.

© 2024 Bentham Science Publishers | Privacy Policy