Skip to main content
SpringerLink
Log in

Redox-Based Therapeutics for Prevention, Mitigation, and Treatment of Lung Injury Secondary to Radiation Exposure

  • Chapter
  • First Online:
Redox-Active Therapeutics

  • 881 Accesses

Abstract

The lungs are among the most radio-intolerant organs. Prevention, mitigation, and/or treatment of lung damage are crucial to reducing morbidity/mortality following radiation exposure in which the majority or all of the thorax has been exposed. Mechanisms of injury begin at the time of exposure and proceed through a clinically latent period that may last weeks, months, or even years before signs of functional injury that can impart a significant reduction in long-term quality of life. In cases of supratherapeutic exposures, lung injury may progress to fulminant organ failure and mortality. At the molecular and cellular levels, damage is manifested by oxidative stress and damage to DNA and key signaling molecules, as well as by continuous cell turnover (i.e., apoptosis and proliferation), leading to bioenergetic exhaustion, inflammation, and fibrosis. Although no treatment is currently approved by the U.S. Food and Drug Administration for radiation pneumonitis/fibrosis, redox-based therapeutics have proven to be an attractive strategy because of their ability to modify cell damage and restore redox balance, leading to improved outcomes. Innovative technologies, such as integrated “omics” approaches and spatial imaging with mass spectrometry, offer new avenues for understanding the mechanisms underlying radiation-induced lung injury and identifying novel therapeutic targets for intervention.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mahmood J, Jelveh S, Zaidi A, Doctrow SR, Hill RP. Mitigation of radiation-induced lung injury with EUK-207 and genistein: effects in adolescent rats. Radiat Res. 2013;179:125–34.

    Article  CAS  PubMed  Google Scholar 

  2. Baranov AE, Selidovkin GD, Butturini A, Gale RP. Hematopoietic recovery after 10-Gy acute total body radiation. Blood. 1994;83:596–9.

    CAS  PubMed  Google Scholar 

  3. Uozaki H, Fukayama M, Nakagawa K, et al. The pathology of multi-organ involvement: two autopsy cases from the Tokai-mura criticality accident. Br J Radiol Supp. 2005;27:13–6.

    Article  Google Scholar 

  4. Coggle JE, Lambert BE, Moores SR. Radiation effects in the lung. Environ Health Perspect. 1986;70:261–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gross NJ. Pulmonary effects of radiation therapy. Ann Intern Med. 1977;86:81–92.

    Article  CAS  PubMed  Google Scholar 

  6. Sharplin J, Franko AJ. A quantitative histological study of strain-dependent differences in the effects of irradiation on mouse lung during the intermediate and late phases. Radiat Res. 1989;119:15–31.

    Article  CAS  PubMed  Google Scholar 

  7. Sharplin J, Franko AJ. A quantitative histological study of strain-dependent differences in the effects of irradiation on mouse lung during the early phase. Radiat Res. 1989;119:1–14.

    Article  CAS  PubMed  Google Scholar 

  8. Travis EL, Down JD. Repair in mouse lung after split doses of X rays. Radiat Res. 1981;87:166–74.

    Article  CAS  PubMed  Google Scholar 

  9. Travis EL, Down JD, Holmes SJ, Hobson B. Radiation pneumonitis and fibrosis in mouse lung assayed by respiratory frequency and histology. Radiat Res. 1980;84:133–43.

    Article  CAS  PubMed  Google Scholar 

  10. Poulson JM, Vujaskovic Z, Gillette SM, Chaney EL, Gillette EL. Volume and dose-response effects for severe symptomatic pneumonitis after fractionated irradiation of canine lung. Int J Radiat Biol. 2000;76:463–8.

    Article  CAS  PubMed  Google Scholar 

  11. Garofalo M, Bennett A, Farese AM, et al. The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model. Health Phys. 2014;106:56–72.

    Article  CAS  PubMed  Google Scholar 

  12. Jackson IL, Xu PT, Nguyen G, et al. Characterization of the dose response relationship for lung injury following acute radiation exposure in three well-established murine strains: developing an interspecies bridge to link animal models with human lung. Health Phys. 2014;106:48–55.

    Article  CAS  PubMed  Google Scholar 

  13. Jackson IL, Goswami C, Katz BP, Vujaskovic Z. Gene expression profiling identifies differences in early tissue respones to radiation among murine strains with distinct phenotypic expression of lung injury. In: 58th Annual meeting of the Radiation Research Society. Rio Grande, Puerto Rico; 2012.

    Google Scholar 

  14. Jackson IL, Vujaskovic Z, Down JD. Revisiting strain-related differences in radiation sensitivity of the mouse lung: recognizing and avoiding the confounding effects of pleural effusions. Radiat Res. 2010;173:10–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jackson IL, Vujaskovic Z, Down JD. A further comparison of pathologies after thoracic irradiation among different mouse strains: finding the best preclinical model for evaluating therapies directed against radiation-induced lung damage. Radiat Res. 2011;175:510–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jackson IL, Xu P, Hadley C, et al. A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule. Health Phys. 2012;103:463–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. O’Neill P, Wardman P. Radiation chemistry comes before radiation biology. Int J Radiat Biol. 2009;85:9–25.

    Article  PubMed  CAS  Google Scholar 

  18. Klammer H, Mladenov E, Li F, Iliakis G. Bystander effects as manifestation of intercellular communication of DNA damage and of the cellular oxidative status. Cancer Lett. 2015;356:58–71.

    Article  CAS  PubMed  Google Scholar 

  19. Matzinger P. Essay 1: the Danger model in its historical context. Scand J Immunol. 2001;54:4–9.

    Article  CAS  PubMed  Google Scholar 

  20. Gallucci S, Matzinger P. Danger signals: SOS to the immune system. Curr Opin Immunol. 2001;13:114–9.

    Article  CAS  PubMed  Google Scholar 

  21. McBride WH, Chiang CS, Olson JL, et al. A sense of danger from radiation. Radiat Res. 2004;162:1–19.

    Article  CAS  PubMed  Google Scholar 

  22. Carter C, Jones J, Jackson I, et al. Using MALDI MSI to enabling biomarker identification and medical countermeasure development for radiation induced lung injury. In: Annual Meeting of the Radiation Research Society; 2014 September 21, 2014; Las Vegas; 2014

    Google Scholar 

  23. Catala A. Lipid peroxidation of membrane phospholipids generates hydroxy-alkenals and oxidized phospholipids active in physiological and/or pathological conditions. Chem Phys Lipids. 2009;157:1–11.

    Article  CAS  PubMed  Google Scholar 

  24. Reisz JA, Bansal N, Qian J, Zhao W, Furdui CM. Effects of ionizing radiation on biological molecules-mechanisms of damage and emerging methods of detection. Antioxid Redox Signal. 2014;21:260–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Schaue D, McBride WH. Links between innate immunity and normal tissue radiobiology. Radiat Res. 2010;173:406–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhou D, Shao L, Spitz DR. Reactive oxygen species in normal and tumor stem cells. Adv Cancer Res. 2014;122:1–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dayal D, Martin SM, Owens KM, et al. Mitochondrial complex II dysfunction can contribute significantly to genomic instability after exposure to ionizing radiation. Radiat Res. 2009;172:737–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kim HR, Won SJ, Fabian C, Kang MG, Szardenings M, Mitochondrial SMG, DNA. Aberrations and pathophysiological implications in hematopoietic diseases, chronic inflammatory diseases, and cancers. Ann Lab Med. 2015;35:1–14.

    Article  PubMed  CAS  Google Scholar 

  29. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94:909–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hei TK, Zhou H, Ivanov VN, et al. Mechanism of radiation-induced bystander effects: a unifying model. J Pharm Pharmacol. 2008;60:943–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chen S, Zhao Y, Han W, et al. Mitochondria-dependent signalling pathway are involved in the early process of radiation-induced bystander effects. Br J Cancer. 2008;98:1839–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sedelnikova OA, Nakamura A, Kovalchuk O, et al. DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Cancer Res. 2007;67:4295–302.

    Article  CAS  PubMed  Google Scholar 

  33. Belyakov OV, Mitchell SA, Parikh D, et al. Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away. Proc Natl Acad Sci U S A. 2005;102:14203–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Batinic-Haberle I, Rajic Z, Tovmasyan A, et al. Diverse functions of cationic Mn(III) N-substituted pyridylporphyrins, recognized as SOD mimics. Free Radic Biol Med. 2011;51:1035–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mothersill C, Seymour C. Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells. Int J Radiat Biol. 1997;71:421–7.

    Article  CAS  PubMed  Google Scholar 

  36. Yang G, Wu L, Chen S, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs radiation-induced bystander effect. Br J Cancer. 2009;100:1912–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rubin P, Johnston CJ, Williams JP, McDonald S, Finkelstein JN. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys. 1995;33:99–109.

    Article  CAS  PubMed  Google Scholar 

  38. Schaue D, Kachikwu EL, McBride WH. Cytokines in radiobiological responses: a review. Radiat Res. 2012;178:505–23.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Fleckenstein K, Zgonjanin L, Chen L, et al. Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Radiat Oncol Biol Phys. 2007;68:196–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Antonadou D, Coliarakis N, Synodinou M, et al. Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced-stage lung cancer. Int J Radiat Oncol Biol Phys. 2001;51:915–22.

    Article  CAS  PubMed  Google Scholar 

  41. Antonadou D, Petridis A, Synodinou M, et al. Amifostine reduces radiochemotherapy-induced toxicities in patients with locally advanced non-small cell lung cancer. Semin Oncol. 2003;30:2–9.

    Article  CAS  PubMed  Google Scholar 

  42. Komaki R, Lee JS, Milas L, et al. Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer: report of a randomized comparative trial. Int J Radiat Oncol Biol Phys. 2004;58:1369–77.

    Article  CAS  PubMed  Google Scholar 

  43. Vujaskovic Z, Feng QF, Rabbani ZN, Anscher MS, Samulski TV, Brizel DM. Radioprotection of lungs by amifostine is associated with reduction in profibrogenic cytokine activity. Radiat Res. 2002;157:656–60.

    Article  CAS  PubMed  Google Scholar 

  44. Vujaskovic Z, Thrasher BA, Jackson IL, Brizel MB, Brizel DM. Radioprotective effects of amifostine on acute and chronic esophageal injury in rodents. Int J Radiat Oncol Biol Phys. 2007;69:534–40.

    Article  CAS  PubMed  Google Scholar 

  45. Ozturk B, Egehan I, Atavci S, Kitapci M. Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: a double-blind randomized trial. Int J Radiat Oncol Biol Phys. 2004;58:213–9.

    Article  CAS  PubMed  Google Scholar 

  46. Kaya V, Yazkan R, Yildirim M, et al. The relation of radiation-induced pulmonary fibrosis with stress and the efficiency of antioxidant treatment: an experimental study. Med Sci Monit. 2014;20:290–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Rabbani ZN, Batinic-Haberle I, Anscher MS, et al. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury. Int J Radiat Oncol Biol Phys. 2007;67:573–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rabbani ZN, Salahuddin FK, Yarmolenko P, et al. Low molecular weight catalytic metalloporphyrin antioxidant AEOL 10150 protects lungs from fractionated radiation. Free Radic Res. 2007;41:1273–82.

    Article  CAS  PubMed  Google Scholar 

  49. Garofalo MC, Ward AA, Farese AM, et al. A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in mitigating radiation-induced lung damage. Health Phys. 2014;106:73–83.

    Article  CAS  PubMed  Google Scholar 

  50. Christofidou-Solomidou M, Tyagi S, Tan KS, et al. Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice. BMC Cancer. 2011;11:269.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Christofidou-Solomidou M, Tyagi S, Pietrofesa R, et al. Radioprotective role in lung of the flaxseed lignan complex enriched in the phenolic secoisolariciresinol diglucoside (SDG). Radiat Res. 2012;178:568–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Day RM, Barshishat-Kupper M, Mog SR, et al. Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation. J Radiat Res. 2008;49:361–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Calveley VL, Jelveh S, Langan A, et al. Genistein can mitigate the effect of radiation on rat lung tissue. Radiat Res. 2010;173:602–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mahmood J, Jelveh S, Calveley V, Zaidi A, Doctrow SR, Hill RP. Mitigation of radiation-induced lung injury by genistein and EUK-207. Int J Radiat Biol. 2011;87:889–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Medina J, Buck C, Pavlovic R, et al. Optimal dose and duration of BIO 300 for mitigating radiation induced lung injury in C57L/J mice. In: Annual Meeting of the Radiation Research Society; 2014 September 21, 2014; Las Vegas; 2014

    Google Scholar 

  56. Gao F, Fish BL, Szabo A, et al. Short-term treatment with a SOD/catalase mimetic, EUK-207, mitigates pneumonitis and fibrosis after single-dose total-body or whole-thoracic irradiation. Radiat Res. 2012;178:468–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, et al. A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury. Free Radic Biol Med. 2002;33:857–63.

    Article  CAS  PubMed  Google Scholar 

  58. Gauter-Fleckenstein B, Fleckenstein K, Owzar K, Jiang C, Batinic-Haberle I, Vujaskovic Z. Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection. Free Radic Biol Med. 2008;44:982–9.

    Article  CAS  PubMed  Google Scholar 

  59. Gauter-Fleckenstein B, Fleckenstein K, Owzar K, et al. Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage. Free Radic Biol Med. 2010;48:1034–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Gauter-Fleckenstein B, Reboucas JS, Fleckenstein K, et al. Robust rat pulmonary radioprotection by a lipophilic Mn N-alkylpyridylporphyrin, MnTnHex-2-PyP(5+). Redox Biol. 2014;2:400–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Patt HM, Tyree EB, Straube RL, Smith DE. Cysteine protection against X irradiation. Science. 1949;110:213–4.

    Article  CAS  PubMed  Google Scholar 

  62. Delanian S, Balla-Mekias S, Lefaix JL. Striking regression of chronic radiotherapy damage in a clinical trial of combined pentoxifylline and tocopherol. J Clin Oncol. 1999;17:3283–90.

    CAS  PubMed  Google Scholar 

  63. Lefaix JL, Delanian S, Vozenin MC, Leplat JJ, Tricaud Y, Martin M. Striking regression of subcutaneous fibrosis induced by high doses of gamma rays using a combination of pentoxifylline and alpha-tocopherol: an experimental study. Int J Radiat Oncol Biol Phys. 1999;43:839–47.

    Article  CAS  PubMed  Google Scholar 

  64. Baillet F, Housset M, Michelson AM, Puget K. Treatment of radiofibrosis with liposomal superoxide dismutase. Preliminary results of 50 cases. Free Radic Res Commun. 1986;1:387–94.

    Article  CAS  PubMed  Google Scholar 

  65. Delanian S, Baillet F, Huart J, Lefaix JL, Maulard C, Housset M. Successful treatment of radiation-induced fibrosis using liposomal Cu/Zn superoxide dismutase: clinical trial. Radiother Oncol. 1994;32:12–20.

    Article  CAS  PubMed  Google Scholar 

  66. Delanian S, Lefaix JL. Complete healing of severe osteoradionecrosis with treatment combining pentoxifylline, tocopherol and clodronate. Br J Radiol. 2002;75:467–9.

    Article  CAS  PubMed  Google Scholar 

  67. Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys. 2011;80:832–9.

    Article  PubMed  Google Scholar 

  68. Hille A, Christiansen H, Pradier O, et al. Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft [et al.] 2005;181:606-14.

    Google Scholar 

  69. Gothard L, Cornes P, Brooker S, et al. Phase II study of vitamin E and pentoxifylline in patients with late side effects of pelvic radiotherapy. Radiother Oncol. 2005;75:334–41.

    Article  CAS  PubMed  Google Scholar 

  70. Delanian S, Lefaix JL. Current management for late normal tissue injury: radiation-induced fibrosis and necrosis. Semin Radiat Oncol. 2007;17:99–107.

    Article  PubMed  Google Scholar 

  71. Sekine I, Sumi M, Ito Y, et al. Retrospective analysis of steroid therapy for radiation-induced lung injury in lung cancer patients. Radiother Oncol. 2006;80:93–7.

    Article  CAS  PubMed  Google Scholar 

  72. Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB. Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 2010;15:360–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969;244:6049–55.

    CAS  PubMed  Google Scholar 

  74. Petkau A. Radiation protection by superoxide dismutase. Photochem Photobiol. 1978;28:765–74.

    Article  CAS  PubMed  Google Scholar 

  75. Symonyan MA, Nalbandyan RM. The effect of x-rays on properties of superoxide dismutase. Biochem Biophys Res Commun. 1979;90:1207–13.

    Article  CAS  PubMed  Google Scholar 

  76. McCord JM, Fridovich I. The utility of superoxide dismutase in studying free radical reactions. I. Radicals generated by the interaction of sulfite, dimethyl sulfoxide, and oxygen. J Biol Chem. 1969;244:6056–63.

    CAS  PubMed  Google Scholar 

  77. Miriyala S, Spasojevic I, Tovmasyan A, et al. Manganese superoxide dismutase, MnSOD and its mimics. Biochim Biophys Acta. 1822;2012:794–814.

    Google Scholar 

  78. Batinic-Haberle I, Tovmasyan A, Roberts ER, Vujaskovic Z, Leong KW, Spasojevic I. SOD therapeutics: latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways. Antioxid Redox Signal. 2014;20:2372–415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Emerit J, Michelson AM, Robert HG, et al. [Superoxide dismutase treatment of 2 cases of radiation-induced sclerosis]. Sem Hop. 1983;59:277–81.

    CAS  PubMed  Google Scholar 

  80. Lefaix JL, Delanian S, Leplat JJ, et al. Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study. Int J Radiat Oncol Biol Phys. 1996;35:305–12.

    Article  CAS  PubMed  Google Scholar 

  81. Stickle RL, Epperly MW, Klein E, Bray JA, Greenberger JS. Prevention of irradiation-induced esophagitis by plasmid/liposome delivery of the human manganese superoxide dismutase transgene. Radiat Oncol Investig. 1999;7:204–17.

    Article  CAS  PubMed  Google Scholar 

  82. Epperly MW, Travis EL, Sikora C, Greenberger JS. Manganese [correction of Magnesium] superoxide dismutase (MnSOD) plasmid/liposome pulmonary radioprotective gene therapy: modulation of irradiation-induced mRNA for IL-I, TNF-alpha, and TGF-beta correlates with delay of organizing alveolitis/fibrosis. Biol Blood Marrow Transplant. 1999;5:204–14.

    Article  CAS  PubMed  Google Scholar 

  83. Day BJ. Catalytic antioxidants: a radical approach to new therapeutics. Drug Discov Today. 2004;9:557–66.

    Article  CAS  PubMed  Google Scholar 

  84. Jaramillo MC, Briehl MM, Batinic-Haberle I, Tome ME. Manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin acts as a pro-oxidant to inhibit electron transport chain proteins, modulate bioenergetics, and enhance the response to chemotherapy in lymphoma cells. Free Radic Biol Med. 2015.

    Google Scholar 

  85. Jackson IL, Zhang X, Hadley C, et al. Temporal expression of hypoxia-regulated genes is associated with early changes in redox status in irradiated lung. Free Radic Biol Med. 2012;53:337–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yakovlev VA, Rabender CS, Sankala H, et al. Proteomic analysis of radiation-induced changes in rat lung: Modulation by the superoxide dismutase mimetic MnTE-2-PyP(5+). Int J Radiat Oncol Biol Phys. 2010;78:547–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhang Y, Zhang X, Rabbani ZN, Jackson IL, Vujaskovic Z. Oxidative stress mediates radiation lung injury by inducing apoptosis. Int J Radiat Oncol Biol Phys. 2012;83:740–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Fu XL, Huang H, Bentel G, et al. Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V(30) and transforming growth factor beta. Int J Radiat Oncol Biol Phys. 2001;50:899–908.

    Article  CAS  PubMed  Google Scholar 

  89. Weitner T, Kos I, Sheng H, et al. Comprehensive pharmacokinetic studies and oral bioavailability of two Mn porphyrin-based SOD mimics, MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+). Free Radic Biol Med. 2013.

    Google Scholar 

  90. Jackson IL, Chen L, Batinic-Haberle I, Vujaskovic Z. Superoxide dismutase mimetic reduces hypoxia-induced O2*-, TGF-beta, and VEGF production by macrophages. Free Radic Res. 2007;41:8–14.

    Article  CAS  PubMed  Google Scholar 

  91. Murigi FN, Hung C, Salimi S, et al. Dose optimization study of AEOL 10150 in mitigation of radiation induced lung injury in CBA/J mice. In: Annual Meeting of the Radiation Research Society; 2014; Las Vegas; 2014.

    Google Scholar 

  92. Carter CL, Jones JW, Jackson IL, et al. MALDI-MSI Lipidomic Investigation into the Delayed Effect of Acute Radiation Exposure: The Lung Syndrome and the Efficacy of a Medical Countermeasure. In: American Society of Mass Spectrometry Annual Meeting; 2014; Baltimore; 2014.

    Google Scholar 

  93. Carter CL, MacVittie TJ, Kane MA. MALDI-MSI: Biomarker discovery for radiation exposures. In: Three encyclopedia, systems biology; 2014

    Google Scholar 

  94. Jones JW, Li F, Carter CL, et al. identification of lipid biomarkers from mouse lung tissue via the use of UPC2 tandem mass spectrometry. In: American Society of Mass Spectrometry Annual Meeting; 2014; Baltimore; 2014.

    Google Scholar 

  95. Jones JW, Li F, Carter CL, et al. Targeted and discovery-based mass spectrometry metabolomics for biomarker identification and validation in mouse and non-human primate radiation models. Las Vegas: Radiation Research Society; 2014.

    Google Scholar 

  96. Zwacka RM, Dudus L, Epperly MW, Greenberger JS, Engelhardt JF. Redox gene therapy protects human IB-3 lung epithelial cells against ionizing radiation-induced apoptosis. Hum Gene Ther. 1998;9:1381–6.

    Article  CAS  PubMed  Google Scholar 

  97. Epperly MW, Gretton JE, Sikora CA, et al. Mitochondrial localization of superoxide dismutase is required for decreasing radiation-induced cellular damage. Radiat Res. 2003;160:568–78.

    Article  CAS  PubMed  Google Scholar 

  98. Epperly M, Bray J, Kraeger S, et al. Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Ther. 1998;5:196–208.

    Article  CAS  PubMed  Google Scholar 

  99. Epperly MW, Epstein CJ, Travis EL, Greenberger JS. Decreased pulmonary radiation resistance of manganese superoxide dismutase (MnSOD)-deficient mice is corrected by human manganese superoxide dismutase-Plasmid/Liposome (SOD2-PL) intratracheal gene therapy. Radiat Res. 2000;154:365–74.

    Article  CAS  PubMed  Google Scholar 

  100. Epperly MW, Defilippi S, Sikora C, Gretton J, Kalend A, Greenberger JS. Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation. Gene Ther. 2000;7:1011–8.

    Article  CAS  PubMed  Google Scholar 

  101. Epperly MW, Tyurina YY, Nie S, et al. MnSOD-plasmid liposome gene therapy decreases ionizing irradiation-induced lipid peroxidation of the esophagus. In Vivo. 2005;19:997–1004.

    CAS  PubMed  Google Scholar 

  102. Niu Y, Shen H, Epperly M, et al. Protection of esophageal multi-lineage progenitors of squamous epithelium (stem cells) from ionizing irradiation by manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) gene therapy. In Vivo. 2005;19:965–74.

    CAS  PubMed  Google Scholar 

  103. Epperly MW, Gretton JA, DeFilippi SJ, et al. Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmid/liposome (SOD2-PL) gene therapy. Radiat Res. 2001;155:2–14.

    Article  CAS  PubMed  Google Scholar 

  104. Epperly MW, Kagan VE, Sikora CA, et al. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation. Int J Cancer. 2001;96:221–31.

    Article  CAS  PubMed  Google Scholar 

  105. Tarhini AA, Belani CP, Luketich JD, et al. A phase I study of concurrent chemotherapy (paclitaxel and carboplatin) and thoracic radiotherapy with swallowed manganese superoxide dismutase plasmid liposome protection in patients with locally advanced stage III non-small-cell lung cancer. Hum Gene Ther. 2011;22:336–42.

    Article  CAS  PubMed  Google Scholar 

  106. Ha CT, Li XH, Fu D, Xiao M, Landauer MR. Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation. Radiat Res. 2013;180:316–25.

    Article  CAS  PubMed  Google Scholar 

  107. McCord JM. Therapeutic control of free radicals. Drug Discov Today. 2004;9:781–2.

    Article  PubMed  Google Scholar 

  108. Travis EL, Rachakonda G, Zhou X, et al. NRF2 deficiency reduces life span of mice administered thoracic irradiation. Free Radic Biol Med. 2011;51:1175–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lee JC, Krochak R, Blouin A, et al. Dietary flaxseed prevents radiation-induced oxidative lung damage, inflammation and fibrosis in a mouse model of thoracic radiation injury. Cancer Biol Ther. 2009;8:47–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Pietrofesa R, Turowski J, Tyagi S, et al. Radiation mitigating properties of the lignan component in flaxseed. BMC Cancer. 2013;13:179.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bentzen SM. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer. 2006;6:702–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, 21202, USA

    Isabel L. Jackson & Zeljko Vujaskovic

Authors
  1. Isabel L. Jackson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zeljko Vujaskovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabel L. Jackson .

Editor information

Editors and Affiliations

  1. Duke University School of Medicine, Durham, North Carolina, USA

    Ines Batinić-Haberle

  2. Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil

    Júlio S. Rebouças

  3. Duke University School of Medicine, Durham, North Carolina, USA

    Ivan Spasojević

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Jackson, I.L., Vujaskovic, Z. (2016). Redox-Based Therapeutics for Prevention, Mitigation, and Treatment of Lung Injury Secondary to Radiation Exposure. In: Batinić-Haberle, I., Rebouças, J., Spasojević, I. (eds) Redox-Active Therapeutics. Oxidative Stress in Applied Basic Research and Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-30705-3_28

Download citation

Publish with us

Policies and ethics

Search

Navigation