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  • ISSN 1674-8301
  • CN 32-1810/R
Volume 29 Issue 3
Apr.  2015
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Guoliang Meng, Jing Wang, Yujiao Xiao, Wenli Bai, Liping Xie, Liyang Shan, Philip K Moore, Yong Ji. GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats[J]. The Journal of Biomedical Research, 2015, 29(3): 203-213. DOI: 10.7555/JBR.28.20140037
Citation: Guoliang Meng, Jing Wang, Yujiao Xiao, Wenli Bai, Liping Xie, Liyang Shan, Philip K Moore, Yong Ji. GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats[J]. The Journal of Biomedical Research, 2015, 29(3): 203-213. DOI: 10.7555/JBR.28.20140037
shu

GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats

  • 1.

    The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine,Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China

  • 2.

    Neurobiology Group, Life Sciences Institute and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

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  • Received Date: March 02, 2014
    Abstract
  • Hydrogen sulfide (H2S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to determine the protective effect of slow-releasing H2S donor GYY4137 on myocardial ischemia and reperfusion (I/R) injury and to investigate the possible signaling mechanisms involved. Male Sprague-Dawley rats were treated with GYY4137 at 12.5 mg/(kg?day), 25 mg/(kg?day) or 50 mg/(kg?day) intraperitoneally for 7 days. Then, rats were subjected to 30 minutes of left anterior descending coronary artery occlusion followed by reperfusion for 24 hours. We found that GYY4137 increased the cardiac ejection fraction and fractional shortening, reduced the ischemia area, alleviated histological injury and decreased plasma creatine kinase after myocardial I/R. Both H2S concentration in plasma and cystathionine-c-lyase (CSE) activity in the myocardium were enhanced in the GYY4137 treated groups. GYY4137 also decreased malondialdehyde and myeloperoxidase levels in serum, attenuated superoxide anion level and suppressed phosphorylation of mitogen activated protein kinases in the myocardium after I/R. Meanwhile, GYY4137 increased the expression of Bcl-2 but decreased the expression of Bax, caspase-3 activity and apoptosis in the myocardium. The data suggest that GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis.
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    Periodical cited type(55)

    1. Hou Y, Lv B, Du J, et al. Sulfide regulation and catabolism in health and disease. Signal Transduct Target Ther, 2025, 10(1): 174. DOI:10.1038/s41392-025-02231-w
    2. Hou Y, Lv B, Du J, et al. Sulfide regulation and catabolism in health and disease. Signal Transduct Target Ther, 2025, 10(1): 174. DOI:10.1038/s41392-025-02231-w
    3. Alotaibi K, Arulkumaran N, Dyson A, et al. Therapeutic strategies to ameliorate mitochondrial oxidative stress in ischaemia-reperfusion injury: A narrative review. Clin Sci (Lond), 2025, 139(3): 259-80. DOI:10.1042/CS20242074
    4. Pagliaro P, Weber NC, Femminò S, et al. Gasotransmitters and noble gases in cardioprotection: unraveling molecular pathways for future therapeutic strategies. Basic Res Cardiol, 2024, 119(4): 509-544. DOI:10.1007/s00395-024-01061-1
    5. Jin YQ, Yuan H, Liu YF, et al. Role of hydrogen sulfide in health and disease. MedComm (2020), 2024, 5(9): e661. DOI:10.1002/mco2.661
    6. Pan S, Yan H, Zhu J, et al. GYY4137, as a slow-releasing H2S donor, ameliorates sodium deoxycholate-induced chronic intestinal barrier injury and gut microbiota dysbiosis. Front Pharmacol, 2024, 15: 1476407. DOI:10.3389/fphar.2024.1476407
    7. Sun X, Wu S, Mao C, et al. Therapeutic Potential of Hydrogen Sulfide in Ischemia and Reperfusion Injury. Biomolecules, 2024, 14(7): 740. DOI:10.3390/biom14070740
    8. Farzaei MH, Ramezani-Aliakbari F, Ramezani-Aliakbari M, et al. Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury. Naunyn Schmiedebergs Arch Pharmacol, 2023, 396(8): 1633-1646. DOI:10.1007/s00210-023-02469-7
    9. Farzaei MH, Ramezani-Aliakbari F, Ramezani-Aliakbari M, et al. Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury. Naunyn Schmiedebergs Arch Pharmacol, 2023, 396(8): 1633-1646. DOI:10.1007/s00210-023-02469-7
    10. Hu Q, Lukesh JC 3rd. H2S Donors with Cytoprotective Effects in Models of MI/R Injury and Chemotherapy-Induced Cardiotoxicity. Antioxidants (Basel), 2023, 12(3): 650. DOI:10.3390/antiox12030650
    11. Zhou M, Chen JY, Chao ML, et al. S-nitrosylation of c-Jun N-terminal kinase mediates pressure overload-induced cardiac dysfunction and fibrosis. Acta Pharmacol Sin, 2022, 43(3): 602-612. DOI:10.1038/s41401-021-00674-9
    12. Khattak S, Rauf MA, Khan NH, et al. Hydrogen Sulfide Biology and Its Role in Cancer. Molecules, 2022, 27(11): 3389. DOI:10.3390/molecules27113389
    13. Zhou M, Chen JY, Chao ML, et al. S-nitrosylation of c-Jun N-terminal kinase mediates pressure overload-induced cardiac dysfunction and fibrosis. Acta Pharmacol Sin, 2022, 43(3): 602-612. DOI:10.1038/s41401-021-00674-9
    14. Khattak S, Rauf MA, Khan NH, et al. Hydrogen Sulfide Biology and Its Role in Cancer. Molecules, 2022, 27(11): 3389. DOI:10.3390/molecules27113389
    15. McCook O, Denoix N, Radermacher P, et al. H2S and Oxytocin Systems in Early Life Stress and Cardiovascular Disease. J Clin Med, 2021, 10(16): 3484. DOI:10.3390/jcm10163484
    16. McCook O, Denoix N, Radermacher P, et al. H2S and Oxytocin Systems in Early Life Stress and Cardiovascular Disease. J Clin Med, 2021, 10(16): 3484. DOI:10.3390/jcm10163484
    17. Zhang Y, Gong W, Xu M, et al. Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3. Int J Mol Sci, 2021, 22(21): 11893. DOI:10.3390/ijms222111893
    18. Testai L, Brancaleone V, Flori L, et al. Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis. Antioxidants (Basel), 2021, 10(6): 910. DOI:10.3390/antiox10060910
    19. Denoix N, McCook O, Ecker S, et al. The Interaction of the Endogenous Hydrogen Sulfide and Oxytocin Systems in Fluid Regulation and the Cardiovascular System. Antioxidants (Basel), 2020, 9(8): 748. DOI:10.3390/antiox9080748
    20. Pieretti JC, Junho CVC, Carneiro-Ramos MS, et al. H2S- and NO-releasing gasotransmitter platform: A crosstalk signaling pathway in the treatment of acute kidney injury. Pharmacol Res, 2020, 161: 105121. DOI:10.1016/j.phrs.2020.105121
    21. Soo E, Marsh C, Steiner R, et al. Optimizing organs for transplantation; advancements in perfusion and preservation methods. Transplant Rev (Orlando), 2020, 34(1): 100514. DOI:10.1016/j.trre.2019.100514
    22. Chen LJ, Ning JZ, Cheng F, et al. Comparison of Intraperitoneal and Intratesticular GYY4137 Therapy for the Treatment of Testicular Ischemia Reperfusion Injury in Rats. Curr Med Sci, 2020, 40(2): 332-338. DOI:10.1007/s11596-020-2180-6
    23. Yurinskaya MM, Krasnov GS, Kulikova DA, et al. H2S counteracts proinflammatory effects of LPS through modulation of multiple pathways in human cells. Inflamm Res, 2020, 69(5): 481-495. DOI:10.1007/s00011-020-01329-x
    24. Kang SC, Sohn EH, Lee SR. Hydrogen Sulfide as a Potential Alternative for the Treatment of Myocardial Fibrosis. Oxid Med Cell Longev, 2020, 2020: 4105382. DOI:10.1155/2020/4105382
    25. Newton TD, Pluth MD. Development of a hydrolysis-based small-molecule hydrogen selenide (H2Se) donor. Chem Sci, 2019, 10(46): 10723-10727. DOI:10.1039/c9sc04616j
    26. Zheng W, Liu C. The cystathionine γ-lyase/hydrogen sulfide pathway mediates the trimetazidine-induced protection of H9c2 cells against hypoxia/reoxygenation-induced apoptosis and oxidative stress. Anatol J Cardiol, 2019, 22(3): 102-111. DOI:10.14744/AnatolJCardiol.2019.83648
    27. Wang W, Liu H, Lu Y, et al. Controlled-releasing hydrogen sulfide donor based on dual-modal iron oxide nanoparticles protects myocardial tissue from ischemia-reperfusion injury. Int J Nanomedicine, 2019, 14: 875-888. DOI:10.2147/IJN.S186225
    28. Cao X, Ding L, Xie ZZ, et al. A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?. Antioxid Redox Signal, 2019, 31(1): 1-38. DOI:10.1089/ars.2017.7058
    29. Zheng Q, Pan L, Ji Y. H 2S protects against diabetes-accelerated atherosclerosis by preventing the activation of NLRP3 inflammasome. J Biomed Res, 2019, 34(2): 94-102. DOI:10.7555/JBR.33.20190071
    30. Maassen H, Hendriks KDW, Venema LH, et al. Hydrogen sulphide-induced hypometabolism in human-sized porcine kidneys. PLoS One, 2019, 14(11): e0225152. DOI:10.1371/journal.pone.0225152
    31. Wang W, Liu H, Lu Y, et al. Controlled-releasing hydrogen sulfide donor based on dual-modal iron oxide nanoparticles protects myocardial tissue from ischemia-reperfusion injury. Int J Nanomedicine, 2019, 14: 875-888. DOI:10.2147/IJN.S186225
    32. Cao X, Ding L, Xie ZZ, et al. A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?. Antioxid Redox Signal, 2019, 31(1): 1-38. DOI:10.1089/ars.2017.7058
    33. Zheng W, Liu C. The cystathionine γ-lyase/hydrogen sulfide pathway mediates the trimetazidine-induced protection of H9c2 cells against hypoxia/reoxygenation-induced apoptosis and oxidative stress. Anatol J Cardiol, 2019, 22(3): 102-111. DOI:10.14744/AnatolJCardiol.2019.83648
    34. Luo H, Song S, Chen Y, et al. Inhibitor 1 of Protein Phosphatase 1 Regulates Ca2+/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes. Oxid Med Cell Longev, 2019, 2019: 2193019. DOI:10.1155/2019/2193019
    35. Cao X, Zhang W, Moore PK, et al. Protective Smell of Hydrogen Sulfide and Polysulfide in Cisplatin-Induced Nephrotoxicity. Int J Mol Sci, 2019, 20(2): 313. DOI:10.3390/ijms20020313
    36. Van Dingenen J, Pieters L, Vral A, et al. The H2S-Releasing Naproxen Derivative ATB-346 and the Slow-Release H2S Donor GYY4137 Reduce Intestinal Inflammation and Restore Transit in Postoperative Ileus. Front Pharmacol, 2019, 10: 116. DOI:10.3389/fphar.2019.00116
    37. Zhang Y, Liu X, Zhang L, et al. Metformin Protects against H2O2-Induced Cardiomyocyte Injury by Inhibiting the miR-1a-3p/GRP94 Pathway. Mol Ther Nucleic Acids, 2018, 13: 189-197. DOI:10.1016/j.omtn.2018.09.001
    38. Ning JZ, Li W, Cheng F, et al. The protective effects of GYY4137 on ipsilateral testicular injury in experimentally varicocele-induced rats. Exp Ther Med, 2018, 15(1): 433-439. DOI:10.3892/etm.2017.5417
    39. Zeng C, Jiang W, Zheng R, et al. Cardioprotection of tilianin ameliorates myocardial ischemia-reperfusion injury: Role of the apoptotic signaling pathway. PLoS One, 2018, 13(3): e0193845. DOI:10.1371/journal.pone.0193845
    40. Zhou X, Tang S, Hu K, et al. DL-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress. Sleep Breath, 2018, 22(3): 853-863. DOI:10.1007/s11325-018-1656-0
    41. Sun X, Wang W, Dai J, et al. A Long-Term and Slow-Releasing Hydrogen Sulfide Donor Protects against Myocardial Ischemia/Reperfusion Injury. Sci Rep, 2017, 7(1): 3541. DOI:10.1038/s41598-017-03941-0
    42. Szabo C, Papapetropoulos A. International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors. Pharmacol Rev, 2017, 69(4): 497-564. DOI:10.1124/pr.117.014050
    43. Sun Y, Huang Y, Yu W, et al. Sulfhydration-associated phosphodiesterase 5A dimerization mediates vasorelaxant effect of hydrogen sulfide. Oncotarget, 2017, 8(19): 31888-31900. DOI:10.18632/oncotarget.16649
    44. Pang Z, Zhao W, Yao Z. Cardioprotective Effects of Nicorandil on Coronary Heart Disease Patients Undergoing Elective Percutaneous Coronary Intervention. Med Sci Monit, 2017, 23: 2924-2930. DOI:10.12659/msm.902324
    45. Bazhanov N, Escaffre O, Freiberg AN, et al. Broad-Range Antiviral Activity of Hydrogen Sulfide Against Highly Pathogenic RNA Viruses. Sci Rep, 2017, 7: 41029. DOI:10.1038/srep41029
    46. Sun Y, Huang Y, Yu W, et al. Sulfhydration-associated phosphodiesterase 5A dimerization mediates vasorelaxant effect of hydrogen sulfide. Oncotarget, 2017, 8(19): 31888-31900. DOI:10.18632/oncotarget.16649
    47. Cao X, Bian JS. The Role of Hydrogen Sulfide in Renal System. Front Pharmacol, 2016, 7: 385. DOI:10.3389/fphar.2016.00385
    48. Tian XH, Liu CL, Jiang HL, et al. Cardioprotection provided by Echinatin against ischemia/reperfusion in isolated rat hearts. BMC Cardiovasc Disord, 2016, 16: 119. DOI:10.1186/s12872-016-0294-3
    49. Xu J, Tang Y, Bei Y, et al. miR-19b attenuates H2O2-induced apoptosis in rat H9C2 cardiomyocytes via targeting PTEN. Oncotarget, 2016, 7(10): 10870-8. DOI:10.18632/oncotarget.7678
    50. Haase T, Börnigen D, Müller C, et al. Systems Medicine as an Emerging Tool for Cardiovascular Genetics. Front Cardiovasc Med, 2016, 3: 27. DOI:10.3389/fcvm.2016.00027
    51. Cao X, Bian JS. The Role of Hydrogen Sulfide in Renal System. Front Pharmacol, 2016, 7: 385. DOI:10.3389/fphar.2016.00385
    52. Tian XH, Liu CL, Jiang HL, et al. Cardioprotection provided by Echinatin against ischemia/reperfusion in isolated rat hearts. BMC Cardiovasc Disord, 2016, 16: 119. DOI:10.1186/s12872-016-0294-3
    53. Xu J, Tang Y, Bei Y, et al. miR-19b attenuates H2O2-induced apoptosis in rat H9C2 cardiomyocytes via targeting PTEN. Oncotarget, 2016, 7(10): 10870-8. DOI:10.18632/oncotarget.7678
    54. Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms, 2015, 3(4): 866-89. DOI:10.3390/microorganisms3040866
    55. Singh SB, Lin HC. Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract. Microorganisms, 2015, 3(4): 866-89. DOI:10.3390/microorganisms3040866

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    Yong Ji
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      The Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine,Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China

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