Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
November 2013 Volume 32 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November 2013 Volume 32 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Cardioprotective effects of exenatide against oxidative stress-induced injury

  • Authors:
    • Guanglei Chang
    • Dongying Zhang
    • Hui Yu
    • Peng Zhang
    • Ying Wang
    • Aihua Zheng
    • Shu Qin
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
  • Pages: 1011-1020
    |
    Published online on: August 27, 2013
       https://doi.org/10.3892/ijmm.2013.1475
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Myocardial ischemia/reperfusion (MI/R) leads to oxidative stress, which may in turn lead to myocardial injury. In the present study, we investigated the effects of exenatide, a glucagon-like peptide-1 (GLP-1) analogue, on oxidative stress-induced injury in vitro and in vivo. In in vitro experiments, H9c2 cells were incubated with exenatide to determine the direct cytoprotective effects of exenatide following exposure to hydrogen peroxide (H2O2). Pre-treatment with exenatide (1 nM), prior to H2O2 exposure, increased cell viability and inhibited H2O2‑induced reactive oxygen species (ROS) production. Exenatide also decreased the levels of lactate dehydrogenase (LDH) and creatine kinase‑MB (CK‑MB) in the cultured supernatants, as well as those of malondialdehyde (MDA) in the H9c2 cells and increased the total superoxide dismutase (T‑SOD) levels in the H9c2 cells. In in vivo experiments, an animal model of MI/R was induced by coronary occlusion. Pre-treatment with exenatide (10 µg/kg/day) protected the rat hearts from MI/R-induced injury by decreasing the levels of LDH and CK‑MB in plasma, increasing the levels of catalase, T-SOD and glutathione peroxidase (GSH-Px) in the heart and decreasing the MDA levels in the rats with MI/R-induced injury. Exenatide also reduced the infarct size and enhanced cardiac function in the rats with MI/R-induced injury. Moreover, pre-treatment with exenatide inhibited cardiomyocyte apoptosis, increased Aktserine473 and Badserine136 phosphorylation and decreased cleaved caspase‑3 expression in vitro and in vivo; however, these effects were attenuated by the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. Our results suggest that exenatide exerts significant cardioprotective effects against oxidative stress-induced injury in vitro and in vivo. The mechanisms involved may be attributed to the scavenging of oxidative stress products, such as ROS, the increase in the concentrations of antioxidant defense enzymes and the inhibition of cardiomyocyte apoptosis. The anti‑apoptotic effects of exenatide were, at least in part, associated with the activation of the PI3K/Akt signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Acar E, Ural D, Bildirici U, Sahin T and Yılmaz I: Diabetic cardiomyopathy. Anadolu Kardiyol Derg. 11:732–737. 2011.

2 

Zweier JL and Talukder MA: The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res. 70:181–190. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Zhao ZQ: Oxidative stress-elicited myocardial apoptosis during reperfusion. Curr Opin Pharmacol. 4:159–165. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Gottlieb RA: Cell death pathways in acute ischemia/reperfusion injury. J Cardiovasc Pharmacol Ther. 16:233–238. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G and Anversa P: Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest. 74:86–107. 1996.PubMed/NCBI

6 

Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM and Tikkanen I: Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol. 280:H2726–H2731. 2001.PubMed/NCBI

7 

Garber AJ: Novel GLP-1 receptor agonists for diabetes. Expert Opin Investig Drugs. 21:45–57. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Davidson JA: Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. Cleve Clin J Med. 76(Suppl 5): S28–S38. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Lorber D: GLP-1 receptor agonists: effects on cardiovascular risk reduction. Cardiovasc Ther. Jul 30–2012.(Epub ahead of print).

10 

Mundil D, Cameron-Vendrig A and Husain M: GLP-1 receptor agonists: a clinical perspective on cardiovascular effects. Diab Vasc Dis Res. 9:95–108. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Chiquette E, Toth PP, Ramirez G, Cobble M and Chilton R: Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers. Vasc Health Risk Manag. 8:621–629. 2012.PubMed/NCBI

12 

Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, Verlaan CW, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G and Hoefer IE: Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol. 53:501–510. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Laviola L, Leonardini A, Melchiorre M, Orlando MR, Peschechera A, Bortone A, Paparella D, Natalicchio A, Perrini S and Giorgino F: Glucagon-like peptide-1 counteracts oxidative stress-dependent apoptosis of human cardiac progenitor cells by inhibiting the activation of the c-Jun N-terminal protein kinase signaling pathway. Endocrinology. 153:5770–5781. 2012. View Article : Google Scholar

14 

Ravassa S, Zudaire A, Carr RD and Díez J: Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. Am J Physiol Heart Circ Physiol. 300:H1361–H372. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Younce CW, Burmeister MA and Ayala JE: Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a. Am J Physiol Cell Physiol. 304:C508–C518. 2013. View Article : Google Scholar

16 

Kumar S, Kain V and Sitasawad SL: High glucose-induced Ca2+ overload and oxidative stress contribute to apoptosis of cardiac cells through mitochondrial dependent and independent pathways. Biochim Biophys Acta. 1820:907–920. 2012.

17 

Fishbein MC, Meerbaum S, Rit J, Lando U, Kanmatsuse K, Mercier JC, Corday E and Ganz W: Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. Am Heart J. 101:593–600. 1981. View Article : Google Scholar

18 

Loesser KE, Kukreja RC, Kazziha SY, Jesse RL and Hess ML: Oxidative damage to the myocardium: a fundamental mechanism of myocardial injury. Cardioscience. 2:199–216. 1991.PubMed/NCBI

19 

Suzuki K, Murtuza B, Sammut IA, Latif N, et al: Heat shock protein 72 enhances manganese superoxide dismutase activity during myocardial ischemia-reperfusion injury, associated with mitochondrial protection and apoptosis reduction. Circulation. 106:I270–I276. 2002.

20 

Peng X and Li Y: Induction of cellular glutathione-linked enzymes and catalase by the unique chemoprotective agent, 3H-1,2-dithiole-3-thione in rat cardiomyocytes affords protection against oxidative cell injury. Pharmacol Res. 45:491–497. 2002. View Article : Google Scholar

21 

Li C, Liu Z, Tian J, Li G, Jiang W, Zhang G, Chen F, Lin P and Ye Z: Protective roles of Asperosaponin VI, a triterpenesaponin isolated from Dipsacusasper Wall on acute myocardial infarction in rats. Eur J Pharmacol. 627:235–241. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Li J, Shao ZH, Xie JT, Wang CZ, Ramachandran S, Yin JJ, Aung H, Li CQ, Qin G, Vanden Hoek T and Yuan CS: The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes. Arch Pharm Res. 35:1259–1267. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Jin HB, Yang YB, Song YL, Zhang YC and Li YR: Protective roles of quercetin in acute myocardial ischemia and reperfusion injury in rats. Mol Biol Rep. 39:11005–11009. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Cai Y, Hu X, Yi B, Zhang T and Wen Z: Glucagon-like peptide-1 receptor agonist protects against hyperglycemia-induced cardiocytes injury by inhibiting high mobility group box 1 expression. Mol Biol Rep. 39:10705–10711. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Fontes JP, Gonçalves M and Ribeiro VG: Serum markers for ischemic myocardial damage. Rev Port Cardiol. 18:1129–1136. 1999.(Portuguese).

26 

Xie Y, Wang SX, Sha WW, Zhou X, Wang WL, Han LP, Li DQ and Yu DM: Effects and mechanism of glucagon-like peptide-1 on injury of rats cardiomyocytes induced by hypoxia-reoxygenation. Clin Med J. 121:2134–2138. 2008.PubMed/NCBI

27 

Chinda K, Chattipakorn S and Chattipakorn N: Cardioprotective effects of incretin during ischaemia-reperfusion. Diab Vasc Dis Res. 9:256–269. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Khalil PN, Neuhof C, Huss R, Pollhammer M, Khalil MN, Neuhof H, Fritz H and Siebeck M: Calpain inhibition reduces infarct size and improves global hemodynamics and left ventricular contractility in a porcine myocardial ischemia/reperfusion model. Eur J Pharmacol. 528:124–131. 2005. View Article : Google Scholar

29 

Hausenloy DJ and Yellon DM: New directions for protecting the heart against ischaemia-reperfusion injury: targeting the reperfusion injury s alvage kinase (RISK)-pathway. Cardiovasc Res. 61:448–460. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Mullonkal CJ and Toledo-Pereyra LH: Akt in ischemia and reperfusion. J Invest Surg. 20:195–203. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Fujio Y, Nguyen T, Wencker D, Kitsis RN and Walsh K: Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation. 101:660–667. 2000.PubMed/NCBI

32 

Matsui T, Tao J, del Monte F, Lee KH, Li L, Picard M, Force TL, Franke TF, Hajjar RJ and Rosenzweig A: Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation. 104:330–335. 2001. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chang G, Zhang D, Yu H, Zhang P, Wang Y, Zheng A and Qin S: Cardioprotective effects of exenatide against oxidative stress-induced injury. Int J Mol Med 32: 1011-1020, 2013.
APA
Chang, G., Zhang, D., Yu, H., Zhang, P., Wang, Y., Zheng, A., & Qin, S. (2013). Cardioprotective effects of exenatide against oxidative stress-induced injury. International Journal of Molecular Medicine, 32, 1011-1020. https://doi.org/10.3892/ijmm.2013.1475
MLA
Chang, G., Zhang, D., Yu, H., Zhang, P., Wang, Y., Zheng, A., Qin, S."Cardioprotective effects of exenatide against oxidative stress-induced injury". International Journal of Molecular Medicine 32.5 (2013): 1011-1020.
Chicago
Chang, G., Zhang, D., Yu, H., Zhang, P., Wang, Y., Zheng, A., Qin, S."Cardioprotective effects of exenatide against oxidative stress-induced injury". International Journal of Molecular Medicine 32, no. 5 (2013): 1011-1020. https://doi.org/10.3892/ijmm.2013.1475
Copy and paste a formatted citation
x
Spandidos Publications style
Chang G, Zhang D, Yu H, Zhang P, Wang Y, Zheng A and Qin S: Cardioprotective effects of exenatide against oxidative stress-induced injury. Int J Mol Med 32: 1011-1020, 2013.
APA
Chang, G., Zhang, D., Yu, H., Zhang, P., Wang, Y., Zheng, A., & Qin, S. (2013). Cardioprotective effects of exenatide against oxidative stress-induced injury. International Journal of Molecular Medicine, 32, 1011-1020. https://doi.org/10.3892/ijmm.2013.1475
MLA
Chang, G., Zhang, D., Yu, H., Zhang, P., Wang, Y., Zheng, A., Qin, S."Cardioprotective effects of exenatide against oxidative stress-induced injury". International Journal of Molecular Medicine 32.5 (2013): 1011-1020.
Chicago
Chang, G., Zhang, D., Yu, H., Zhang, P., Wang, Y., Zheng, A., Qin, S."Cardioprotective effects of exenatide against oxidative stress-induced injury". International Journal of Molecular Medicine 32, no. 5 (2013): 1011-1020. https://doi.org/10.3892/ijmm.2013.1475
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team