Skip to main content
SpringerLink
Log in

Ischemia–Reperfusion Injury: Molecular Mechanisms of Pathogenesis and Methods of Their Correction

  • REDOX REGULATION OF METABOLIC PROCESSES
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract—Ischemia–reperfusion is a cascade of complex and interrelated pathological processes underlying many human diseases, including such socially significant diseases as stroke, myocardial infarction, acute renal failure, etc. The present review considers modern ideas about the main biochemical and signal-regulatory processes in the cell under conditions of ischemia–reperfusion. Both generally accepted and newly developed ways of ischemia–reperfusion lesion correction aimed at different chains of this pathological process are considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. Hardev Ramandeep Singh Girn., Ahilathirunayagam S., Mavor A.I.D., Homer-Vanniasinkam S. 2007. Reperfusion syndrome: Cellular mechanisms of microvascular dysfunction and potential therapeutic strategies. Vasc. Endovasc. Surg. 41, 277–293.

    Article  Google Scholar 

  2. Soares R.O.S., Losada D.M., Jordani M.C., Évora P., Castro-E-Silva O. 2019. Ischemia/reperfusion injury revisited: An overview of the latest pharmacological strategies. Int. J. Mol. Sci. 20, 5034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dar W.A., Sullivan E., Bynon J.S., Eltzschig H., Ju C. 2019. Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms. Liver Int. 39, 788–801.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chen Z., Tian R., She Z., Cai J., Li H. 2020. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radical Biol. Med. 152, 116–141.

    Article  CAS  Google Scholar 

  5. Wu M.Y., Yiang G.T., Liao W.T., Tsai A.P.Y., Cheng Y.L., Cheng P.W., Li C.Y., Li C.J. 2018. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol. Biochem. 46, 1650–1667.

    Article  CAS  PubMed  Google Scholar 

  6. Eltzschig H.K., Eckle T. 2011. Ischemia and reperfusion—from mechanism to translation. Nat. Med. 17, 1391–1401.

    Article  CAS  PubMed  Google Scholar 

  7. Mishra P.K., Adameova A., Hill J.A., Baines C.P., Kang P.M., Downey J.M., Narula J., Takahashi M., Abbate A., Piristine H.C., Kar S., Su S., Higa J.K., Kawasaki N.K., Matsui T. 2019. Guidelines for evaluating myocardial cell death. Am. J. Physiol., Heart Circ. Physiol. 317, H891–H922.

    Article  CAS  PubMed  Google Scholar 

  8. Bauer T.M., Murphy E. 2020. Role of mitochondrial calcium and the permeability transition pore in regulating cell death. Circ. Res. 126, 280–293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. van Golen R.F., Reiniers M.J., Marsman G., Alles L.K., van Rooyen D.M., Petri B., Van der Mark V.A., van Beek A.A., Meijer B., Maas M.A., Zeerleder S., Verheij J., Farrell G.C., Luken B.M., Teoh N.C., van Gulik T.M., Murphy M.P., Heger M. 2019. The damage-associated molecular pattern HMGB1 is released early after clinical hepatic ischemia/reperfusion. Biochim. Biophys. Acta, Mol. Basis Dis. 1865, 1192–1200.

    Article  CAS  Google Scholar 

  10. Gong L., Pan Q., Yang N. 2020. Autophagy and inflammation regulation in acute kidney injury. Front. Physiol. 11, 576463.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vorobjeva N.V. 2020. Neutrophil extracellular traps: New aspects. Moscow Univ. Biol. Sci. Bull. 75, 173–188.

    Article  CAS  PubMed  Google Scholar 

  12. Kim S.W., Lee H., Lee H.K., Kim I.D., Lee J.K. 2019. Neutrophil extracellular trap induced by HMGB1 exacerbates damages in the ischemic brain. Acta Neuropathol. Commun. 7, 94.

    Article  PubMed  Google Scholar 

  13. Raedschelders K., Ansley D.M., Chen D.D.Y. 2012. The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion. Pharmacol. Ther. 133, 230–255.

    Article  CAS  PubMed  Google Scholar 

  14. Zhou T., Chuang C.C., Zuo L. 2015. Molecular characterization of reactive oxygen species in myocardial ischemia−reperfusion injury. Biomed. Res. Int. 2015, 864946.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bugger H., Pfeil K. 2020. Mitochondrial ROS in myocardial ischemia reperfusion and remodeling. Biochim. Biophys. Acta, Mol. Basis Dis. 1866, 165768.

    Article  CAS  Google Scholar 

  16. Matsushima S., Sadoshima J. 2022. Yin and Yang of NADPH oxidases in myocardial ischemia–reperfusion. Antioxidants. 11, 1069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lambeth J.D., Krause K.H., Clark R.A. 2008. NOX enzymes as novel targets for drug development. Semin. Immunopathol. 30, 339–363.

    Article  CAS  PubMed  Google Scholar 

  18. Loukogeorgakis S.P., Van Den Berg M.J., Sofat R., Nitsch D., Charakida M., Haiyee B., De Groot E., MacAllister R.J., Kuijpers T.W., Deanfield J.E. 2010. Role of NADPH oxidase in endothelial ischemia/reperfusion injury in humans. Circulation. 121, 2310–2316.

    Article  CAS  PubMed  Google Scholar 

  19. Nakagiri A., Sunamoto M., Murakami M. 2007. NA-DPH oxidase is involved in ischaemia/reperfusion-induced damage in rat gastric mucosa via ROS production—role of NADPH oxidase in rat stomachs. Inflammopharmacology. 15, 278–281.

    Article  CAS  PubMed  Google Scholar 

  20. Förstermann U., Sessa W.C. 2012. Nitric oxide synthases: Regulation and function. Eur. Heart J. 33, 829–837.

    Article  PubMed  Google Scholar 

  21. Xu F., Mack C.P., Quandt K.S., Shlafer M., Massey V., Hultquist D.E. 1993. Pyrroloquinoline quinone acts with flavin reductase to reduce ferryl myoglobin in vitro and protects isolated heart from reoxygenation injury. Biochem. Biophys. Res. Commun. 193, 434–439.

    Article  CAS  PubMed  Google Scholar 

  22. McLeod L.L., Alayash A.I. 1999. Detection of a ferrylhemoglobin intermediate in an endothelial cell model after hypoxia−reoxygenation. Am. J. Physiol., Heart Circ. Physiol. 277, H92–H99.

    Article  CAS  Google Scholar 

  23. Ruan Y., Zeng J., Jin Q., Chu M., Ji K., Wang Z., Li L. 2020. Endoplasmic reticulum stress serves an important role in cardiac ischemia/reperfusion injury (review). Exp. Ther. Med. 20, 260.

    Article  Google Scholar 

  24. Zhou H., Toan S. 2020. Pathological roles of mitochondrial oxidative stress and mitochondrial dynamics in cardiac microvascular ischemia/reperfusion injury. Biomolecules. 10, 85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lipskaia L., Keuylian Z., Blirando K., Mougenot N., Jacquet A., Rouxel C., Sghairi H., Elaib Z., Blaise R., Adnot S., Hajjar R.J., Chemaly E.R., Limon I., Bobe R. 2014. Expression of Sarco (Endo) plasmic reticulum calcium ATPase (SERCA) system in normal mouse cardiovascular tissues, heart failure and atherosclerosis. Biochim. Biophys. Acta. 1843, 2705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang R., Wang M., He S., Sun G., Sun X. 2020. Targeting calcium homeostasis in myocardial ischemia/reperfusion injury: An overview of regulatory mechanisms and therapeutic reagents. Front. Pharmacol. 11, 1–14.

    Google Scholar 

  27. Adams C.J., Kopp M.C., Larburu N., Nowak P.R., Ali M.M.U. 2019. Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1. Front. Mol. Biosci. 6, 1–12.

    Article  Google Scholar 

  28. Kaul S., Methner C., Cao Z., Mishra A. 2022. Mechanisms of the “No-Reflow” phenomenon after acute myocardial infarction. JACC Basic Transl. Sci. 8, 204–220.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Edwards N.J., Hwang C., Marini S., Pagani C.A., Spreadborough P.J., Rowe C.J., Yu P., Mei A., Visser N., Li S., Hespe G.E., Huber A.K., Strong A.L., Shelef M.A., Knight J.S., Davis T.A., Levi B. 2020. The role of neutrophil extracellular traps and TLR signaling in skeletal muscle ischemia reperfusion injury. FASEB J. 34, 15753–15770.

    Article  CAS  PubMed  Google Scholar 

  30. Arlati S. 2019. Pathophysiology of acute illness and injury. In Operative Techniques and Recent Advances in Acute Care and Emergency Surgery. Cham: Springer, 11–42.

    Google Scholar 

  31. Granger D.N., Kvietys P.R. 2015. Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol. 6, 524–551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tennant D., Howell N.J. 2014. The role of HIFs in ischemia−reperfusion injury. Hypoxia. 2, 107–115.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Silva-Islas C.A., Maldonado P.D. 2018. Canonical and non-canonical mechanisms of Nrf2 activation. Pharmacol. Res. 134, 92–99.

    Article  CAS  PubMed  Google Scholar 

  34. Toth R., Warfel N. 2017. Strange bedfellows: nuclear factor, erythroid 2-like 2 (Nrf2) and hypoxia-inducible factor 1 (HIF-1) in tumor hypoxia. Antioxidants. 6, 27.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gallagher B.M., Phelan S.A. 2007. Investigating transcriptional regulation of Prdx6 in mouse liver cells. Free Radical Biol. Med. 42, 1270–1277.

    Article  CAS  Google Scholar 

  36. Park Y.-H., Kim S.-U., Kwon T.-H., Kim J.-M., Song I.-S., Shin H.-J., Lee B.-K., Bang D.-H., Lee S.-J., Lee D.-S., Chang K.-T., Kim B.-Y., Yu D.-Y. 2016. Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway. Oncogene. 35, 3503–3513.

    Article  CAS  PubMed  Google Scholar 

  37. Guo Q.J., Mills J.N., Bandurraga S.G., Nogueira L.M., Mason N.J., Camp E.R., Larue A.C., Turner D.P., Findlay V.J. 2013. MicroRNA-510 promotes cell and tumor growth by targeting peroxiredoxin1 in breast cancer. Breast Cancer Res. 15, R70.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hopkins B.L., Nadler M., Skoko J.J., Bertomeu T., Pelosi A., Shafaei P.M., Levine K., Schempf A., Pennarun B., Yang B., Datta D., Bucur O., Ndebele K., Oesterreich S., Yang D., Rizzo M.G., Khosravi-Far R., Neumann C.A. 2018. A peroxidase peroxiredoxin 1‑specific redox regulation of the novel FOXO3 microRNA target let-7. Antioxid. Redox Signal. 28, 62–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Joris V., Gomez E.L., Menchi L., Lobysheva I., Di Mauro V., Esfahani H., Condorelli G., Balligand J.-L., Catalucci D., Dessy C. 2018. MicroRNA-199a-3p and microRNA-199a-5p take part to a redundant network of regulation of the NOS (NO synthase)/NO pathway in the endothelium. Arterioscler. Thromb. Vasc. Biol. 38, 2345–2357.

    Article  CAS  PubMed  Google Scholar 

  40. Zheng J., Chen P., Zhong J., Cheng Y., Chen H., He Y., Chen C. 2021. HIF‑1α in myocardial ischemia-reperfusion injury (review). Mol. Med. Rep. 23, 1–9.

    Article  Google Scholar 

  41. Schellinger I.N., Cordasic N., Panesar J., Buchholz B., Jacobi J., Hartner A., Klanke B., Jakubiczka-Smorag J., Burzlaff N., Heinze E., Warnecke C., Raaz U., Willam C., Tsao P.S., Eckardt K.U., Amann K., Hilgers K.F. 2017. Hypoxia inducible factor stabilization improves defective ischemia-induced angiogenesis in a rodent model of chronic kidney disease. Kidney Int. 91, 616–627.

    Article  CAS  PubMed  Google Scholar 

  42. Wigerup C., Påhlman S., Bexell D. 2016. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol. Ther. 164, 152–169.

    Article  CAS  PubMed  Google Scholar 

  43. Koyasu S., Kobayashi M., Goto Y., Hiraoka M., Harada H. 2018. Regulatory mechanisms of hypoxia-inducible factor 1 activity: Two decades of knowledge. Cancer Sci. 109, 560–571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. BelAiba R.S., Bonello S., Zahringer C., Schmidt S., Hess J., Kietzmann T., Gorlach A. 2007. Hypoxia up-regulates hypoxia-inducible factor-1 transcription by involving phosphatidylinositol 3-kinase and nuclear factor B in pulmonary artery smooth muscle cells. Mol. Biol. Cell. 18, 4691–4697.

    Article  PubMed  PubMed Central  Google Scholar 

  45. van Uden P., Kenneth N.S., Webster R., Müller H.A., Mudie S., Rocha S. 2011. Evolutionary conserved regulation of HIF-1β by NF-κB. PLoS Genet. 7, e1001285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhang C., Liu J., Wang J., Zhang T., Xu D., Hu W., Feng Z. 2021. The interplay between tumor suppressor p53 and hypoxia signaling pathways in cancer. Front. Cell Dev. Biol. 9, 648808.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Potteti H.R., Noone P.M., Tamatam C.R., Ankireddy A., Noel S., Rabb H., Reddy S.P. 2021. Nrf2 mediates hypoxia-inducible HIF1a activation in kidney tubular epithelial cells. Am. J. Physiol.: Heart Circ. Physiol., Renal Physiol. 320, F464–F474.

    Article  CAS  Google Scholar 

  48. Cai S.J., Liu Y., Han S., Yang C. 2019. Brusatol, an NRF2 inhibitor for future cancer therapeutic. Cell Biosci. 9, 9–11.

    Article  Google Scholar 

  49. Burgos R.A., Alarcón P., Quiroga J., Manosalva C., Hancke J. 2021. Andrographolide, an anti-inflammatory multitarget drug: All roads lead to cellular metabolism. Molecules. 26, 5.

    Article  CAS  Google Scholar 

  50. Lin J., Fan L., Han Y., Guo J., Hao Z., Cao L., Kang J., Wang X., He J., Li J. 2021. The mTORC1/eIF4E/HIF-1α pathway mediates glycolysis to support brain hypoxia resistance in the Gansu Zokor, Eospalax cansus. Front. Physiol. 12, 626240.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Zang H., Mathew R.O., Cui T. 2020. The dark side of Nrf2 in the heart. Front. Physiol. 11, 1–8.

    Article  Google Scholar 

  52. He F., Ru X., Wen T. 2020. NRF2, a transcription factor for stress response and beyond. Int. J. Mol. Sci. 21, 1–23.

    Article  Google Scholar 

  53. Calvert J.W., Jha S., Gundewar S., Elrod J.W., Ramachandran A., Pattillo C.B., Kevil C.G., Lefer D.J. 2009. Hydrogen sulfide mediates cardioprotection through Nrf2 signaling. Circ. Res. 105, 365–374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Howden R. 2013. Nrf2 and cardiovascular defense. Oxid. Med. Cell Longev. 2013, 1–10.

    Google Scholar 

  55. Chen Q.M. 2021. Nrf2 for cardiac protection: Pharmacological options against oxidative stress. Trends Pharmacol. Sci. 42, 729–744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bardallo G.R., Panisello-Roselló A., Sanchez-Nuno S., Alva N., Roselló-Catafau J., Carbonell T. 2022. Nrf2 and oxidative stress in liver ischemia/reperfusion injury. FEBS J. 289, 5463–5479.

    Article  Google Scholar 

  57. Arfin S., Jha N.K., Jha S.K., Kesari K.K., Ruokolainen J., Roychoudhury S., Rathi B., Kumar D. 2021. Oxidative stress in cancer cell metabolism. Antioxidants. 10, 167–197.

    Article  Google Scholar 

  58. Saha S., Buttari B., Panieri E., Profumo E., Saso L. 2020. An overview of Nrf2 signaling pathway and its role in inflammation. Molecules. 25, 1–31.

    Article  Google Scholar 

  59. Wu J., Sun X., Jiang Z., Jiang J., Xu L., Tian A., Sun X., Meng H., Li Y., Huang W., Jia Y., Wu H. 2020. Protective role of NRF2 in macrovascular complications of diabetes. J. Cell. Mol. Med. 24, 8903–8917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ganner A., Pfeiffer Z.C., Wingendorf L., Kreis S., Klein M., Walz G., Neumann-Haefelin E. 2020. The acetyltransferase p300 regulates NRF2 stability and localization. Biochem. Biophys. Res. Commun. 524, 895–902.

    Article  CAS  PubMed  Google Scholar 

  61. Kim M.J., Jeon J.H. 2022. Recent advances in understanding Nrf2 agonism and its potential clinical application to metabolic and inflammatory diseases. Int. J. Mol. Sci. 23, 2846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang J., Pan W., Zhang Y., Tan M., Yin Y., Li Y., Zhang L., Han L., Bai J., Jiang T., Li H. 2022. Comprehensive overview of Nrf2-related epigenetic regulations involved in ischemia−reperfusion injury. Theranostics. 12, 6626–6645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ngo K.A., Kishimoto K., Davis-Turak J., Pimplaskar A., Cheng Z., Spreafico R., Chen E.Y., Tam A., Ghosh G., Mitchell S., Hoffmann A. 2020. Dissecting the regulatory strategies of NF-κB RelA target genes in the inflammatory response reveals differential transactivation logics. Cell Rep. 30, 2758–2775. e6.

  64. Naguib S., Backstrom J.R., Gil M., Calkins D.J., Rex T.S. 2021. Retinal oxidative stress activates the NRF2/ARE pathway: An early endogenous protective response to ocular hypertension. Redox Biol. 42, 101883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lu J., Wu T., Zhang B., Liu S., Song W., Qiao J., Ruan H. 2021. Types of nuclear localization signals and mechanisms of protein import into the nucleus. Cell Commun. Signal. 19, 1–10.

    Article  Google Scholar 

  66. Mulero M.C., Wang V.Y., Huxford T., Ghosh G. 2019. Genome reading by the NF-kB transcription factors. Nucl. Acids Res. 47, 9967–9989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Albensi B.C. 2019. What is nuclear factor kappa B (NF-κB) Doing in and to the mitochondrion? Front. Cell. Dev. Biol. 7, 1–7.

    Article  Google Scholar 

  68. Oeckinghaus A., Hayden M.S., Ghosh S. 2011. Crosstalk in NF-κB signaling pathways. Nat. Immunol. 12, 695–708.

    Article  CAS  PubMed  Google Scholar 

  69. Jarvis R.M., Hughes S.M., Ledgerwood E.C. 2012. Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells. Free Radic. Biol. Med. 53, 1522–1530.

    Article  CAS  PubMed  Google Scholar 

  70. Howell J.A., Bidwell G.L. 2020. Targeting the NF-κB pathway for therapy of ischemic stroke. Ther. Delivery 11, 113–123.

    Article  CAS  Google Scholar 

  71. Hasan A.A., Kalinina E., Tatarskiy V., Shtil A. 2022. The thioredoxin system of mammalian cells and its modulators. Biomedicines. 10, 1757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ghosh R., Samanta P., Sarkar R., Biswas S., Saha P., Hajra S., Bhowmik A. 2022. Targeting HIF-1α by natural and synthetic compounds: A promising approach for anti-cancer therapeutics development. Molecules. 27, 1–37.

    Article  Google Scholar 

  73. Shi T., Dansen T.B. 2020. Reactive oxygen species induced p53 activation: DNA damage, redox signaling, or both? Antioxidants Redox Signal. 33, 839–859.

    Article  CAS  Google Scholar 

  74. Eriksson S.E., Ceder S., Bykov V.J.N., Wiman K.G. 2019. P53 as a hub in cellular redox regulation and therapeutic target in cancer. J. Mol. Cell. Biol. 11, 330–341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Konrath F., Mittermeier A., Cristiano E., Wolf J., Loewer A. 2020. A systematic approach to decipher crosstalk in the p53 signaling pathway using single cell dynamics. PLoS Comput. Biol. 16, 1–27.

    Article  Google Scholar 

  76. Pan M., Blattner C. 2021. Regulation of P53 by E3S. Cancers (Basel). 13, 1–43.

    Article  Google Scholar 

  77. Ghoneum A., Said N. 2019. PI3K-AKT-mTOR and NFkB pathways in ovarian cancer: Implications for targeted therapeutics. Cancers (Basel). 11, 1757.

    Article  Google Scholar 

  78. Xu F., Na L., Li Y., Chen L. 2020. Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci. 10, 1–12.

    Article  Google Scholar 

  79. Yoshioka K. 2021. Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking. Biochem. Soc. Trans. 49, 893–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Khan H., Singh A., Thapa K., Garg N., Grewal A.K., Singh T.G. 2021. Therapeutic modulation of the phosphatidylinositol 3-kinases (PI3K) pathway in cerebral ischemic injury. Brain Res. 1761, 147399.

    Article  CAS  Google Scholar 

  81. Walkowski B., Kleibert M., Majka M., Wojciechowska M. 2022. Insight into the role of the PI3K/Akt pathway in ischemic injury and post-infarct left ventricular remodeling in normal and diabetic heart. Cells. 11, 1553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tsai P.J., Lai Y.H., Manne R.K., Tsai Y.S., Sarbassov D., Lin H.K. 2022. Akt: A key transducer in cancer. J. Biomed. Sci. 29, 1–17.

    Article  Google Scholar 

  83. Li D., Qu Y., Mao M., Zhang X., Li J., Ferriero D., Mu D. 2009. Involvement of the PTEN–AKT–FOXO3a pathway in neuronal apoptosis in developing rat brain after hypoxia–ischemia. J. Cereb. Blood Flow Metab. 29, 1903–1913.

    Article  CAS  PubMed  Google Scholar 

  84. Yang S., Pang L., Dai W., Wu S., Ren T., Duan Y., Zheng Y., Bi S., Zhang X., Kong J. 2021. Role of forkhead box O proteins in hepatocellular carcinoma biology and progression (review). Front. Oncol. 11, 1–15.

    Google Scholar 

  85. Wu P., Du Y., Xu Z., Zhang S., Liu J., Aa N., Yang Z. 2019. Protective effects of sodium tanshinone IIA sulfonate on cardiac function after myocardial infarction in mice. Am. J. Transl. Res. 11, 351–360.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhang Z., Yao L., Yang J., Wang Z., Du G. 2018. PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia (review). Mol. Med. Rep. 18, 3547–3554.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Yang X.M., Wang Y.S., Zhang J., Li Y., Xu J.F., Zhu J., Zhao W., Chu D.K., Wiedemann P. 2009. Role of PI3K/Akt and MEK/ERK in mediating hypoxia-induced expression of HIF-1α and VEGF in laser-induced rat choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 50, 1873–1879.

    Article  PubMed  Google Scholar 

  88. Karar J., Cerniglia G.J., Lindsten T., Koumenis C., Maity A. 2012. Dual PI3K/mTOR inhibitor NVP-BEZ235 suppresses hypoxia-inducible factor (HIF)-1α expression by blocking protein translation and increases cell death under hypoxia. Cancer Biol. Ther. 13, 1102–1111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Deng H., Chen Y., Li P., Hang Q., Zhang P., Jin Y., Chen M. 2023. PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism: Potential targets to overcome radioresistance in small cell lung cancer. Cancer Pathog. Ther. 1, 56–66.

    Article  Google Scholar 

  90. Bouyahya A., El Allam A., Aboulaghras S., Bakrim S., El Menyiy N., Alshahrani M.M., Al Awadh A.A., Benali T., Lee L.-H., El Omari N., Goh K.W., Ming L.C., Mubarak M.S. 2022. Targeting mTOR as a cancer therapy: Recent advances in natural bioactive compounds and immunotherapy. Cancers (Basel). 14, 5520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kierans S.J., Taylor C.T. 2021. Regulation of glycolysis by the hypoxia-inducible factor (HIF): Implications for cellular physiology. J. Physiol. 599, 23–37.

    Article  CAS  PubMed  Google Scholar 

  92. Fu W., Hall M.N. 2020. Regulation of MTORC2 signaling. Genes (Basel). 11, 1–19.

    Article  Google Scholar 

  93. Huu T.N., Park J., Zhang Y., Park I., Yoon H.J., Woo H.A., Lee S.R. 2021. Redox regulation of PTEN by peroxiredoxins. Antioxidants. 10, 1–14.

    Google Scholar 

  94. Wang Y., Zhang X., ling B., He C., Xia Q., Chen F., Miyamori I., Yang Z., Fan C. 2013. Molecular detection of trisomy 21 by bicolor competitive fluorescent PCR. J. Clin. Lab. Anal. 27, 245–248.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Olthof P.B., Reiniers M.J., Dirkes M.C., Van Gulik T.M., Heger M., Van Golen R.F. 2015. Protective mechanisms of hypothermia in liver surgery and transplantation. Mol. Med. 21, 833–846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Jaeschke H., Woolbright B.L. 2012. Current strategies to minimize hepatic ischemia−reperfusion injury by targeting reactive oxygen species. Transplant. Rev. 26, 103–114.

    Article  Google Scholar 

  97. Deng H., Han H.S., Cheng D., Sun G.H., Yenari M.A. 2003. Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke. 34, 2495–2501.

    Article  PubMed  Google Scholar 

  98. Sangaletti R., Tamames I., Yahn S.L., Choi J.S., Lee J.K., King C., Rajguru S.M. 2023. Mild therapeutic hypothermia protects against inflammatory and proapoptotic processes in the rat model of cochlear implant trauma. Hear Res. 428, 108680.

    Article  PubMed  Google Scholar 

  99. Yanamoto H., Hong S.C., Soleau S., Kassell N.F., Lee K.S. 1996. Mild postischemic hypothermia limits cerebral injury following transient focal ischemia in rat neocortex. Brain Res. 718, 207–211.

    Article  CAS  PubMed  Google Scholar 

  100. Polderman K.H. 2008. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet. 371, 1955–1969.

    Article  PubMed  Google Scholar 

  101. Chen-Yoshikawa T.F. 2021. Ischemia–reperfusion injury in lung transplantation. Cells. 10, 1333.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Edelman J.J.B., Seco M., Dunne B., Matzelle S.J., Murphy M., Joshi P., Yan T.D., Wilson M.K., Bannon P.G., Vallely M.P., Passage J. 2013. Custodiol for myocardial protection and preservation: A systematic review. Ann. Cardiothorac. Surg. 2, 717–728.

    PubMed  PubMed Central  Google Scholar 

  103. Kurtz C.C., Lindell S.L., Mangino M.J., Carey H.V. 2006. Hibernation confers resistance to intestinal ischemia−reperfusion injury. Am. J. Physiol.: Gastrointest. Liver Physiol. 291, 895–901.

    Google Scholar 

  104. Dark J. 2005. Annual lipid cycles in hibernators: Integration of physiology and behavior. Annu. Rev. Nutr. 25, 469–497.

    Article  CAS  PubMed  Google Scholar 

  105. Andrews M.T. 2007. Advances in molecular biology of hibernation in mammals. BioEssays. 29, 431–440.

    Article  CAS  PubMed  Google Scholar 

  106. Zingarelli B., Hake P.W., O’Connor M., Burroughs T.J., Wong H.R., Solomkin J.S., Lentsch A.B. 2009. Lung injury after hemorrhage is age dependent: Role of peroxisome proliferator-activated receptor γ. Crit. Care Med. 37, 1978–1987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Plotnikov E.Y. 2021. Ischemic preconditioning of the kidney. Bull. Exp. Biol. Med. 171, 567–571.

    Article  CAS  PubMed  Google Scholar 

  108. Kloner R.A., Jennings R.B. 2001. Consequences of brief ischemia: Stunning, preconditioning, and their clinical implications. Part 1. Circulation. 104, 2981–2989.

    Article  CAS  PubMed  Google Scholar 

  109. Yoon Y.E., Lee K.S., Choi K.H., Kim K.H., Yang S.C., Han W.K. 2015. Preconditioning strategies for kidney ischemia reperfusion injury: Implications of the “time-window” in remote ischemic preconditioning. PLoS One. 10, e0124130.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Lang J.A., Kim J. 2022. Remote ischaemic preconditioning—translating cardiovascular benefits to humans. J. Physiol. 600, 3053–3067.

    Article  CAS  PubMed  Google Scholar 

  111. Zhao Z.Q., Corvera J.S., Halkos M.E., Kerendi F., Wang N.P., Guyton R.A., Vinten-Johansen J. 2003. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: Comparison with ischemic preconditioning. Am. J. Physiol.: Heart Circ. Physiol. 285, 579–588.

    Google Scholar 

  112. Sengul D. 2021. Connection of reactive oxygen species as an essential actor for the mechanism of phenomena; ischemic preconditioning and postconditioning: Come to age or ripening? North Clin. Istanbul. 8, 644–649.

    Google Scholar 

  113. Khan H., Kashyap A., Kaur A., Singh T.G. 2020. Pharmacological postconditioning: A molecular aspect in ischemic injury. J. Pharm. Pharmacol. 72, 1513–1527.

    Article  CAS  PubMed  Google Scholar 

  114. Terada L.S., Guidot D.M., Leff J.A., Willingham I.R., Hanley M.E., Piermattei D., Repine J.E. 1992. Hypoxia injures endothelial cells by increasing endogenous xanthine oxidase activity. Proc. Natl. Acad. Sci. U. S. A. 89, 3362–3366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Cantu-Medellin N., Kelley E.E. 2013. Xanthine oxidoreductase-catalyzed reactive species generation: a process in critical need of reevaluation. Redox Biol. 1, 353–358.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Bredemeier M., Lopes L.M., Eisenreich M.A., Hickmann S., Bongiorno G.K., D’Avila R., Morsch A.L.B., da Silva Stein F., Campos G.G.D. 2018. Xanthine oxidase inhibitors for prevention of cardiovascular events: A systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc. Disord. 18, 1–11.

    Article  CAS  Google Scholar 

  117. Rastogi R., Geng X., Li F., Ding Y. 2017. NOX activation by subunit interaction and underlying mechanisms in disease. Front. Cell Neurosci. 10, 1–13.

    Article  Google Scholar 

  118. Brandes R.P., Weissmann N., Schröder K. 2014. Nox family NADPH oxidases: Molecular mechanisms of activation. Free Radic. Biol. Med. 76, 208–226.

    Article  CAS  PubMed  Google Scholar 

  119. Waghela B.N., Vaidya F.U., Agrawal Y., Santra M.K., Mishra V., Pathak C. 2021. Molecular insights of NA-DPH oxidases and its pathological consequences. Cell Biochem. Funct. 39, 218–234.

    Article  CAS  PubMed  Google Scholar 

  120. Csányi G., Cifuentes-Pagano E., Al Ghouleh I., Ranayhossaini D.J., Egaña L., Lopes L.R., Jackson H.M., Kelley E.E., Pagano P.J. 2011. Nox2 B-loop peptide, Nox2ds, specifically inhibits Nox2 oxidase. Free Radical Biol. Med. 51, 1116–1125.

    Article  Google Scholar 

  121. Altenhöfer S., Radermacher K.A., Kleikers P.W.M., Wingler K., Schmidt H.H.H.W. 2015. Evolution of NADPH oxidase inhibitors: Selectivity and mechanisms for target engagement. Antioxid. Redox Signal. 23, 406–427.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Kaludercic N., Mialet-Perez J., Paolocci N., Parini A., Di Lisa F. 2014. Monoamine oxidases as sources of oxidants in the heart. J. Mol. Cell Cardiol. 73, 34–42.

    Article  CAS  PubMed  Google Scholar 

  123. Duicu O.M., Lighezan R., Sturza A., Ceausu R.A., Borza C., Vaduva A., Noveanu L., Gaspar M., Ionac A., Feier H., Muntean D.M., Mornos C. 2015. Monoamine oxidases as potential contributors to oxidative stress in diabetes: Time for a study in patients undergoing heart surgery. Biomed. Res. Int. 2015, 515437.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Duarte P., Cuadrado A., León R. 2021. Monoamine oxidase inhibitors: From classic to new clinical approaches. Handb Exp. Pharmacol. 264, 229–259.

    Article  CAS  PubMed  Google Scholar 

  125. Stein A., Bailey S.M. 2013. Redox biology of hydrogen sulfide: Implications for physiology, pathophysiology, and pharmacology. Redox Biol. 1, 32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Kamoun P., Belardinelli M.-C., Chabli A., Lallouchi K., Chadefaux-Vekemans B. 2003. Endogenous hydrogen sulfide overproduction in Down syndrome. Am. J. Med. Genet. A. 116A, 310–311.

    Article  PubMed  Google Scholar 

  127. Szabo C., Ransy C., Módis K., Andriamihaja M., Murghes B., Coletta C., Olah G., Yanagi K., Bouillaud F. 2014. Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part I. Biochemical and physiological mechanisms. Br. J. Pharmacol. 171, 2099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Wu D., Wang J., Li H., Xue M., Ji A., Li Y. 2015. Role of hydrogen sulfide in ischemia−reperfusion injury. Oxid. Med. Cell Longev. 2015, 1–16.

    CAS  Google Scholar 

  129. Szabo C., Papapetropoulos A. 2017. International union of basic and clinical pharmacology. CII: Pharmacological modulation of H2S levels: H2s donors and H2S biosynthesis inhibitors. Pharmacol. Rev. 69, 497–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Meng W., Pei Z., Feng Y., Zhao J., Chen Y., Shi W., Xu Q., Lin F., Sun M., Xiao K. 2017. Neglected role of hydrogen sulfide in sulfur mustard poisoning: Keap1 S-sulfhydration and subsequent Nrf2 pathway activation. Sci. Rep. 7, 9433.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Jiang B., Tang G., Cao K., Wu L., Wang R. 2010. Molecular mechanism for H(2)S-induced activation of K(ATP) channels. Antioxid. Redox Signal. 12, 1167–1178.

    Article  CAS  PubMed  Google Scholar 

  132. Ge S.N., Zhao M.M., Wu D.D., Chen Y., Wang Y., Zhu J.H., Cai W.J., Zhu Y.Z., Zhu Y.C. 2014. Hydrogen sulfide targets EGFR Cys797/Cys798 residues to induce Na(+)/K(+)-ATPase endocytosis and inhibition in renal tubular epithelial cells and increase sodium excretion in chronic salt-loaded rats. Antioxid. Redox Signal. 21, 2061–2082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Tao B.B., Liu S.Y., Zhang C.C., Fu W., Cai W.J., Wang Y., Shen Q., Wang M.J., Chen Y., Zhang L.J., Zhu Y.Z., Zhu Y.C. 2013. VEGFR2 functions as an H2S-targeting receptor protein kinase with its novel Cys1045-Cys1024 disulfide bond serving as a specific molecular switch for hydrogen sulfide actions in vascular endothelial cells. Antioxid. Redox Signal. 19, 448–464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kai S., Tanaka T., Daijo H., Harada H., Kishimoto S., Suzuki K., Takabuchi S., Takenaga K., Fukuda K., Hirota K. 2012. Hydrogen sulfide inhibits hypoxia-but not anoxia-induced hypoxia-inducible factor 1 activation in a von Hippel−Lindau- and mitochondria-dependent manner. Antioxid. Redox Signal. 16, 203–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wang D., Ma Y., Li Z., Kang K., Sun X., Pan S., Wang J., Pan H., Liu L., Liang D., Jiang H. 2012. The role of AKT1 and autophagy in the protective effect of hydrogen sulphide against hepatic ischemia/reperfusion injury in mice. Autophagy. 8, 954–962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Wolfschmitt E.M., Hogg M., Vogt J.A., Zink F., Wachter U., Hezel F., Zhang X., Hoffmann A., Gröger M., Hartmann C., Gässler H., Datzmann T., Merz T., Hellmann A., Kranz C., Calzia E., Radermacher P., Messerer D.A.C. 2023. The effect of sodium thiosulfate on immune cell metabolism during porcine hemorrhage and resuscitation. Front. Immunol. 14, 1–16.

    Article  Google Scholar 

  137. Zorov D.B., Juhaszova M., Sollott S.J. 2014. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 94, 909–950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Kent A.C., El Baradie K.B.Y., Hamrick M.W. 2021. Targeting the mitochondrial permeability transition pore to prevent age-associated cell damage and neurodegeneration. Oxid. Med. Cell. Longev. 2021, 6626484.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Belosludtsev K.N., Dubinin M.V., Belosludtseva N.V., Mironova G.D. 2019. Mitochondrial Ca2+ transport: Mechanisms, molecular structures, and role in cells. Biochemistry (Moscow). 84, 593–607.

    CAS  PubMed  Google Scholar 

  140. Briston T., Selwood D.L., Szabadkai G., Duchen M.R. 2019. Mitochondrial permeability transition: A molecular lesion with multiple drug targets. Trends Pharmacol. Sci. 40, 50–70.

    Article  CAS  PubMed  Google Scholar 

  141. Piot C., Croisille P., Staat P., Thibault H., Rioufol G., Mewton N., Elbelghiti R., Cung T.T., Bonnefoy E., Angoulvant D., Macia C., Raczka F., Sportouch C., Gahide G., Finet G., André-Fouët X., Revel D., Kirkorian G., Monassier J.-P., Derumeaux G., Ovize M. 2008. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N. Engl. J. Med. 359, 473–481.

    Article  CAS  PubMed  Google Scholar 

  142. Rottenberg H., Hoek J.B. 2021. The mitochondrial permeability transition: Nexus of aging, disease and longevity. Cells. 10, 1–23.

    Article  Google Scholar 

  143. Zweier J.L., Flaherty J.T., Weisfeldt M.L. 1987. Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc. Natl. Acad. Sci. U. S. A. 84, 1404–1407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Sharapov M.G., Gudkov S. V., Lankin V.Z. 2021. Hydroperoxide-reducing enzymes in the regulation of free-radical processes. Biochemistry (Moscow). 86, 1256–1274.

    CAS  PubMed  Google Scholar 

  145. Gudkov S.V., Popova N.R., Bruskov V.I. 2015. Radioprotective substances: History, trends and prospects. Biophysics (Moscow). 60, 659–667.

    Article  CAS  Google Scholar 

  146. Orhan G., Yapici N., Yuksel M., Sargin M., Şenay Ş., Yalçin A.S., Aykaç Z., Aka S.A. 2006. Effects of N-acetylcysteine on myocardial ischemia−reperfusion injury in bypass surgery. Heart Vessels. 21, 42–47.

    Article  PubMed  Google Scholar 

  147. Prabhu A., Sujatha D.I., Kanagarajan N., Vijayalakshmi M.A., Ninan B. 2009. Effect of N-acetylcysteine in attenuating ischemic reperfusion injury in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Ann. Vasc. Surg. 23, 645–651.

    Article  CAS  PubMed  Google Scholar 

  148. Karmanova E.E., Chernikov A.V., Popova N.R., Sharapov M.G., Ivanov V.E., Bruskov V.I. 2023. Metformin mitigates radiation toxicity exerting antioxidant and genoprotective properties. Naunyn Schmiedebergs Arch. Pharmacol. AOP, 1–12.

  149. Mohsin A.A., Chen Q., Quan N., Rousselle T., Maceyka M.W., Samidurai A., Thompson J., Hu Y., Li J., Lesnefsky E.J. 2019. Mitochondrial complex I inhibition by metformin limits reperfusion injury. J. Pharmacol. Exp. Ther. 369, 282–290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Bu Y., Peng M., Tang X., Xu X., Wu Y., Chen A.F., Yang X. 2022. Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms. J. Cell. Mol. Med. 26, 4886–4903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Liu W., Wang L., Liu C., Dai Z., Li T., Tang B. 2022. Edaravone ameliorates cerebral ischemia−reperfusion injury by downregulating ferroptosis via the Nrf2/FPN pathway in rats. Biol. Pharm. Bull. 45, 1269–1275.

    Article  CAS  PubMed  Google Scholar 

  152. Bailly C. 2019. Potential use of edaravone to reduce specific side effects of chemo-, radio- and immuno-therapy of cancers. Int. Immunopharmacol. 77, 105967.

    Article  CAS  PubMed  Google Scholar 

  153. Kassab A.A., Aboregela A.M., Shalaby A.M. 2020. Edaravone attenuates lung injury in a hind limb ischemia−reperfusion rat model: A histological, immunohistochemical and biochemical study. Ann. Anat. 228, 151433.

    Article  PubMed  Google Scholar 

  154. Chen C., Li M., Lin L., Chen S., Chen Y., Hong L. 2021. Clinical effects and safety of edaravone in treatment of acute ischaemic stroke: A meta-analysis of randomized controlled trials. J. Clin. Pharm. Ther. 46, 907–917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Fock E.M., Parnova R.G. 2021. Protective effect of mitochondria-targeted antioxidants against inflammatory response to lipopolysaccharide challenge: A review. Pharmaceutics. 13, 1–24.

    Article  Google Scholar 

  156. Skulachev V.P. 2013. Cationic antioxidants as a powerful tool against mitochondrial oxidative stress. Biochem. Biophys. Res. Commun. 441, 275–279.

    Article  CAS  PubMed  Google Scholar 

  157. Plotnikov E.Y., Chupyrkina A.A., Jankauskas S.S., Pevzner I.B., Silachev D.N., Skulachev V.P., Zorov D.B. 2011. Mechanisms of nephroprotective effect of mitochondria-targeted antioxidants under rhabdomyolysis and ischemia/reperfusion. Biochim. Biophys. Acta, Mol. Basis. Dis. 1812, 77–86.

    Article  CAS  Google Scholar 

  158. Silachev D.N., Isaev N.K., Pevzner I.B., Zorova L.D., Stelmashook E.V., Novikova S.V., Plotnikov E.Y., Skulachev V.P., Zorov D.B. 2012. The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk. PLoS One. 7, e51553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Plotnikov E.Y., Zorov D.B. 2019. Pros and cons of use of mitochondria-targeted antioxidants. Antioxidants. 8, 4–9.

    Article  Google Scholar 

  160. Venardos K., Kaye D. 2007. Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: A review. Curr. Med. Chem. 14, 1539–1549.

    Article  CAS  PubMed  Google Scholar 

  161. Turovsky E.A., Mal’tseva V.N., Sarimov R.M., Simakin A.V., Gudkov S.V., Plotnikov E.Y. 2022. Features of the cytoprotective effect of selenium nanoparticles on primary cortical neurons and astrocytes during oxygen-glucose deprivation and reoxygenation. Sci. Rep. 12, 1710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Schanne G., Zoumpoulaki M., Gazzah G., Vincent A., Preud’Homme H., Lobinski R., Demignot S., Seksik P., Delsuc N., Policar C. 2022. Inertness of superoxide dismutase mimics Mn(ii) complexes based on an open-chain ligand, bioactivity, and detection in intestinal epithelial cells. Oxid. Med. Cell Longevity 2022, 3858122.

    Article  Google Scholar 

  163. Batinic-Haberle I., Tovmasyan A., Spasojevic I. 2015. An educational overview of the chemistry, biochemistry and therapeutic aspects of Mn porphyrins—from superoxide dismutation to H2O2-driven pathways. Redox Biol. 5, 43–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Ching H.Y.V., Kenkel I., Delsuc N., Mathieu E., Ivanović-Burmazović I., Policar C. 2016. Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides. J. Inorg. Biochem. 160, 172–179.

    Article  CAS  PubMed  Google Scholar 

  165. Policar C., Bouvet J., Bertrand H.C., Delsuc N. 2022. SOD mimics: From the tool box of the chemists to cellular studies. Curr. Opin. Chem. Biol. 67, 102109.

    Article  CAS  PubMed  Google Scholar 

  166. Wang J., Wang P., Dong C., Zhao Y., Zhou J., Yuan C., Zou L. 2020. Mechanisms of ebselen as a therapeutic and its pharmacology applications. Future Med. Chem. 12, 2123–2142.

    Article  Google Scholar 

  167. Azad G.K., Tomar R.S. 2014. Ebselen, a promising antioxidant drug: mechanisms of action and targets of bi-ological pathways. Mol. Biol. Rep. 41, 4865–4879.

    Article  CAS  PubMed  Google Scholar 

  168. Santi C., Scimmi C., Sancineto L. 2021. Ebselen and analogues: Pharmacological properties and synthetic strategies for their preparation. Molecules. 26, 4230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Ge X., Cao Z., Chu L. 2022. The antioxidant effect of the metal and metal-oxide nanoparticles. Antioxidants. 11, 791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Friedel F.C., Lieb D., Ivanović-Burmazović I. 2012. Comparative studies on manganese-based SOD mimetics, including the phosphate effect, by using global spectral analysis. J. Inorg. Biochem. 109, 26–32.

    Article  CAS  PubMed  Google Scholar 

  171. Yoshikawa T., Naito Y., Ueda S., Oyamada H., Takemura T., Yoshida N., Sugino S., Kondo M. 1990. Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. J. Clin. Gastroenterol. 12 (Suppl. 1), S65–S71.

    Article  PubMed  Google Scholar 

  172. Ambrosio G., Flaherty J.T. 1992. Effects of the superoxide radical scavenger superoxide dismutase, and of the hydroxyl radical scavenger mannitol, on reperfusion injury in isolated rabbit hearts. Cardiovasc. Drugs Ther. 6, 623–632.

    Article  CAS  PubMed  Google Scholar 

  173. Morpurgo E., Cadrobbi R., Morpurgo M., Rigotti P., Schiavon F., Schiavon O., Caliceti P., Ancona E., Veronese F.M. 1996. Protective effect of superoxide dismutase and polyethylene glycol-linked superoxide dismutase against renal warm ischemia/reperfusion injury. Transplantation. 62, 1221–1223.

    Article  CAS  PubMed  Google Scholar 

  174. Kinouchi H., Epstein C.J., Mizui T., Carlson E., Chen S.F., Chan P.H. 1991. Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proc. Natl. Acad. Sci. U. S. A. 88, 11158–11162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Valdivia A., Pérez-Álvarez S., Aroca-Aguilar J.D., Ikuta I., Jordán J. 2009. Superoxide dismutases: A physiopharmacological update. J. Physiol. Biochem. 65, 195–208.

    Article  CAS  PubMed  Google Scholar 

  176. Giardino R., Giavaresi G., Fini M., Torricelli P., Guzzardella G.A. 2002. The role of different chemical modifications of superoxide dismutase in preventing a prolonged muscular ischemia/reperfusion injury. Artif. Cells Blood Substit. Immobil. Biotechnol. 30, 189–198.

    Article  CAS  PubMed  Google Scholar 

  177. Galinanes M., Qiu Y., Ezrin A., Hearse D.J. 1992. PEG-SOD and myocardial protection. Studies in the blood- and crystalloid-perfused rabbit and rat hearts. Circulation. 86, 672–682.

    Article  CAS  PubMed  Google Scholar 

  178. Muizelaar J.P. 1993. Cerebral ischemia−reperfusion injury after severe head injury and its possible treatment with polyethyleneglycol-superoxide dismutase. Ann. Emerg. Med. 22, 1014–1021.

    Article  CAS  PubMed  Google Scholar 

  179. Jiang Y., Arounleut P., Rheiner S., Bae Y., Kabanov A.V., Milligan C., Manickam D.S. 2016. SOD1 nanozyme with reduced toxicity and MPS accumulation. J. Controlled Release. 231, 38–49.

    Article  CAS  Google Scholar 

  180. Cosenza C., Wu G.H., Tuso P.J., Cramer D.V., Makowka L. 1993. Protective effect of polyethylene glycol-conjugated superoxide dismutase for cold ischemia−reperfusion damage in isolated pig livers. Transplant. Proc. 25, 1881–1882.

    CAS  PubMed  Google Scholar 

  181. Pisani A., Sabbatini M., Riccio E., Rossano R., Andreucci M., Capasso C., De Luca V., Carginale V., Bizzarri M., Borrelli A., Schiattarella A., Santangelo M., Mancini A. 2014. Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury. Clin. Exp. Nephrol. 18, 424–431.

    CAS  PubMed  Google Scholar 

  182. Bonetta R. 2018. Potential therapeutic applications of MnSODs and SOD-mimetics. Chemistry. 24, 5032–5041.

    Article  CAS  PubMed  Google Scholar 

  183. Ambrioso G., Weisfeldt M.L., Jacobus W.E., Flaherty J.T. 1987. Evidence for a reversible oxygen radical-mediated component of reperfusion injury: Reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation. 75, 282–291.

    Article  Google Scholar 

  184. Maksimenko A.V., Vavaev A.V. 2012. Antioxidant enzymes as potential targets in cardioprotection and treatment of cardiovascular diseases. enzyme antioxidants: the next stage of pharmacological counterwork to the oxidative stress. Heart Int. 7, hi.2012.e3.

  185. Shaparov M.G., Gudkov S.V., Lankin V.Z., Novoselov V.I. 2021. Role of glutathione peroxidases and peroxiredoxins in free radical-induced pathologies. Biochemistry (Moscow). 86, 1418–1433.

    CAS  Google Scholar 

  186. Sharapov M.G., Goncharov R.G., Parfenyuk S.B., Glushkova O.V., Novoselov V.I. 2022. The role of phospholipase activity of peroxiredoxin 6 in its transmembrane transport and protective properties. Int. J. Mol. Sci. 23, 15265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Sharapov M.G., Novoselov V.I., Ravin V.K. 2016. Construction of a fusion enzyme exhibiting superoxide dismutase and peroxidase activity. Biochemistry (Moscow). 81, 420–427.

    CAS  PubMed  Google Scholar 

  188. Karaduleva E.V., Mubarakshina E.K., Shara-pov M.G., Volkova A.E., Pimenov O.Y., Ravin V.K., Kokoz Y.M., Novoselov V.I. 2016. Cardioprotective effect of modified peroxiredoxins in retrograde perfusion of isolated rat heart under conditions of oxidative stress. Bull. Exp. Biol. Med. 160, 639–642.

    Article  CAS  PubMed  Google Scholar 

  189. Grudinin N. V., Bogdanov V.K., Sharapov M.G., Bunenkov N.S., Mozheiko N.P., Goncharov R.G., Fesenko E.E., Novoselov V.I. 2020. Use of peroxiredoxin for preconditioning of heterotopic heart transplantation in a rat. Vestn. Transplantologii Iskusst. Organov. 22, 132–136.

    Google Scholar 

  190. Palutina O.A., Sharapov M.G., Temnov A.A., Novoselov V.I. 2016. Nephroprotective effect exogenous antioxidant enzymes during ischemia/reperfusion-induced damage of renal tissue. Bull. Exp. Biol. Med. 160, 322–326.

    Article  CAS  PubMed  Google Scholar 

  191. Goncharov R.G., Rogov K.A., Temnov A.A., Novose-lov V.I., Sharapov M.G. 2019. Protective role of exogenous recombinant peroxiredoxin 6 under ischemia−reperfusion injury of kidney. Cell Tissue Res. 378, 319–332.

    Article  CAS  PubMed  Google Scholar 

  192. Sharapov M.G., Goncharov R.G., Filkov G.I., Trofimenko A.V., Boyarintsev V. V., Novoselov V.I. 2020. Comparative study of protective action of exogenous 2-Cys peroxiredoxins (Prx1 and Prx2) under renal ischemia−reperfusion injury. Antioxidants. 9, 1–23.

    Article  Google Scholar 

  193. Gordeeva A.E., Temnov A.A., Charnagalov A.A., Sharapov M.G., Fesenko E.E., Novoselov V.I. 2015. Protective effect of peroxiredoxin 6 in ischemia/reperfusion−induced damage of small intestine. Dig. Dis. Sci. 60, 3610–3619.

    Article  CAS  PubMed  Google Scholar 

  194. Sharapov M.G., Gordeeva A.E., Goncharov R.G., Tikhonova I.V., Ravin V.K., Temnov A.A., Fesenko E.E., Novoselov V.I. 2017. The effect of exogenous peroxiredoxin 6 on the state of mesenteric vessels and the small intestine in ischemia–reperfusion injury. Biophysics (Moscow). 62, 998–1008.

    Article  CAS  Google Scholar 

  195. Novoselov V.I., Ravin V.K., Sharapov M.G., Sofin A.D., Kukushkin N.I., Fesenko E.E. 2011. Modified peroxiredoxins as prototypes of drugs with powerful antioxidant action. Biophysics (Moscow). 56, 836–842.

    Article  Google Scholar 

  196. Simone E.A., Dziubla T.D., Arguiri E., Vardon V., Shuvaev V. V., Christofidou-Solomidou M., Muzykantov V.R. 2009. Loading PEG-catalase into filamentous and spherical polymer nanocarriers. Pharm. Res. 26, 250–260.

    Article  CAS  PubMed  Google Scholar 

  197. Li Z., Wang F., Roy S., Sen C.K., Guan J. 2009. Injectable, highly flexible, and thermosensitive hydrogels capable of delivering superoxide dismutase. Biomacromolecules. 10, 3306–3316.

    Article  CAS  PubMed  Google Scholar 

  198. Gil D., Rodriguez J., Ward B., Vertegel A., Ivanov V., Reukov V. 2017. Antioxidant activity of SOD and catalase conjugated with nanocrystalline ceria. Bioengineering. 4, 18.

    Article  PubMed  PubMed Central  Google Scholar 

  199. Lacramioara L., Diaconu A., Butnaru M., Verestiuc L. 2016. Biocompatible SPIONs with superoxid dismutase/catalase immobilized for cardiovascular applications. IFMBE Proc. 55, 323–326.

    Article  Google Scholar 

Download references

Funding

This work was supported by the Russian Science Foundation (project no. 22-15-00013).

Author information

Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow oblast, Russia

    R. G. Goncharov & M. G. Sharapov

Authors
  1. R. G. Goncharov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. G. Sharapov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. G. Sharapov.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving animals or human participants performed by any of the authors.

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Abbreviations. IR, ischemia–reperfusion; ROS, reactive oxygen species; MDA, malondialdehyde; ETC, electron transport chain; QH2, hydroquinone; XO, xanthine oxidase; XDH, xanthine dehydrogenase; LOOP, lipid hydroperoxides; NHE, Na+/H+ exchanger protein (Na+/H+ Exchanger); NCX, Na+/Ca2+ exchanger protein (Na+/Ca2+ Exchanger); Glut 1/4, glucose transporter type 1 or 4 (Glucose transporter type 1 or 4); EPR/SR, endoplasmic/sarcoplasmic reticulum; MCU, Mitochondrial Ca2+ Uniporter; mPTP, Ca2+-dependent mitochondrial pore (mitochondrial Permeability Transition Pore); DAMP, Damage Associated Molecular Pattern; CypD, cyclophilin D; NET, extracellular neutrophil traps (Neutrophils Eextracellular Traps); SERCA, Ca2+-activated sarco/endoplasmic reticulum ATPase (Sarco/Endoplasmic Reticulum Ca2+-ATPase); SIRS, Systemic Inflammatory Response Syndrome; CARS, Compensatory Anti-inflammatory Response Syndrome; PON, multiple organ failure; HIF, Hypoxia Inducible Factor; NRF2, transcription factor, the main regulator of the antioxidant response (nuclear factor (erythroid-derived 2)-like 2); ARE, Antioxidant Response Element; KEAP1, NRF2 inhibitor (Kelch-like ECH-associated protein); MAPK, mitogen-activated protein kinase; CBP, transcription coactivator protein (CREB-binding protein); HDAC, histone deacetylase (Histone DeACetylase); PI3K, phosphatidylinositol-3-kinase; mTOR, protein kinase, mammalian target of rapamycin; AKT, serine/threonine protein kinase B (RAC-alpha serine/threonine-protein kinase, protein kinase B alpha); NOX, NADPH oxidases; MAO, monoamine oxidase; COX, cytochrome c oxidase; FoxO, transcription factor, target of AKT kinase (forkhead bOX protein O); TLR, Toll-like receptors (Toll-Like Receptor); RTK, receptor with tyrosine kinase activity (Receptor Tyrosin Kinases); PDGF, Platelet-Derived Growth Factor; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; Trx, thioredoxin; Prdx (Prx), peroxiredoxin; RyR, ryanodine receptor; TNFα, tumor necrosis factor α; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goncharov, R.G., Sharapov, M.G. Ischemia–Reperfusion Injury: Molecular Mechanisms of Pathogenesis and Methods of Their Correction. Mol Biol 57, 1143–1164 (2023). https://doi.org/10.1134/S0026893323060067

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893323060067

Keywords:

Search

Navigation