Skip to main content
Log in

Radiomodulators as Agents of Biological Protection against Oxidative Stress under the Influence of Ionizing Radiation

  • Published:
Biology Bulletin Reviews Aims and scope Submit manuscript

Abstract

The potential mechanisms of radioprotective effect of radiomodulators as agents of “biological” protection against oxidative stress in conditions of acute and chronic irradiation at high- and low-dose-rate ionizing radiation are considered. Radiomodulators, as natural antioxidants, prevent lipid peroxidation of cell membranes and reduce radiation toxemia. The radioprotective and radiomitigative properties of natural antioxidants are limited in terms of a dose reduction factor of 1.15–1.2. The dose–effect interrelation of antioxidants has a dome-shaped character; they can be prooxidants under certain conditions. With this mechanism they are also able to reduce acute toxicity of medicines and poisons. Long, low-intensive radiation at more than 100 mSv/year causes the development of oxidative stress with activation of the mechanisms of antioxidant defense upon its further exhaustion with a decrease in the ascorbic acid content in tissues and endogenous reduced thiols. In this case, the use of natural antioxidants allows a reduction in manifestations of oxidative stress via substrate therapy, thereby compensating for vitamin deficiency under the conditions of their intense consumption. At the same time, the delivery of exogenous purine nucleoside favors the synthesis of DNA and RNA in the course of their postradiation repair. In the condition of oxidative stress, the basis of adaptation shifts in the antioxidant system eventually consists of activation of the nuclear factor Nrf2 and NAD-dependent histone deacetylases sirtuins. Via hormesis, plant polyphenols, coumarins, purine nucleosides, and melatonin can modulate the Nrf2 nuclear factor and sirtuin activity and reduce the remote consequences of chronic radiation exposure, such as a reduction of the human lifespan, by a delay of the development of atherosclerosis, cardiovascular, and neurodegenerative diseases, metabolic syndrome, diabetes mellitus, and the risk of carcinogenesis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Abbas, K., Riquier, S., and Drapier, J.C., Peroxiredoxins and sulfiredoxin at the crossroads of the NO and H2O2 signaling pathways, Methods Enzymol., 2013, vol. 527, pp. 113–128.

    CAS  PubMed  Google Scholar 

  2. Abotaleb, M., Samuel, S.M., and Varghese, E., Flavonoids in cancer and apoptosis, Cancers, 2019, vol. 11, no. 1, p. 28.

    CAS  Google Scholar 

  3. Ahmed, S.M.U., Luo, L., Namani, A., et al., Nrf2 signaling pathway: pivotal roles in inflammation, Biochim. Biophys. Acta,Mol. Basis Dis., 2017, vol. 1863, no. 2, pp. 585–597.

    CAS  Google Scholar 

  4. Allard, J.S., Perez, E., Zou, S., and de Cabo, R., Dietary activators of Sirt1, Mol. Cell Endocrinol., 2009, vol. 299, no. 1, pp. 58–63.

    CAS  PubMed  Google Scholar 

  5. Arora, R., Kumar, R., Sharma, A., and Tripathi, R.P., Herbal Radiomodulators: Applications in Medicine, Homeland Defence and Space, Arora, R., Ed., Cambridge, MA: CAB Int., 2008, pp. 1–24.

    Google Scholar 

  6. Baldwin, J. and Grantham, V., Radiation hormesis: historical and current perspectives, J. Nucl. Med. Technol., 2015, vol. 43, no. 4, pp. 242–246.

    PubMed  Google Scholar 

  7. Barjaktarovic, Z., Merl-Pham, J., Azimzadeh, O., et al., Low-dose radiation differentially regulates protein acetylation and histone deacetylase expression in human coronary artery endothelial cells, Int. J. Radiat. Biol., 2017, vol. 93, no. 2, pp. 156–164.

    CAS  PubMed  Google Scholar 

  8. Begum, N., Prasad, N.R., Kanimozhi, G., and Hasan, A.O., Apigenin ameliorates gamma radiation-induced cytogenetic alterations in cultured human blood lymphocytes, Mutat. Res., 2012, vol. 747, no. 1, pp. 71–76.

    CAS  PubMed  Google Scholar 

  9. Bonkowski, M.S. and Sinclair, D.A., Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds, Nat. Rev. Mol. Cell Biol., 2016, vol. 17, no. 11, pp. 679–690.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Bouayed, J. and Bohn, T., Exogenous antioxidants—double-edged swords in cellular redox state. Health beneficial effects at physiologic doses versus deleterious effects at high doses, Oxid. Med. Cell. Longevity, 2010, vol. 3, no. 4, pp. 228–237.

    Google Scholar 

  11. Breitzig, M., Bhimineni, C., Lockey, R., and Kolliputi, N., 4-hydroxy-2-nonenal: a critical target in oxidative stress? Am. J. Physiol.: Cell Physiol., 2016, vol. 311, no. 4, pp. C537–C543.

    Google Scholar 

  12. Brown, S.L., Kolozsvary, A., Liu, J., et al., Antioxidant diet supplementation starting 24 hours after exposure reduces radiation lethality, Radiat. Res., 2010, vol. 173, pp. 462–468.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Calabrese, V., Cornelius, C., Dinkova-Kostova, A.T., et al., Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders, Antioxid. Redox Signaling, 2010, vol. 13, no. 11, pp. 1763–1811.

  14. Campbell, N.K., Fitzgerald, H.K., Fletcher, J.M., and Dunne, A., Plant-derived polyphenols modulate human dendritic cell metabolism and immune function via AMPK-dependent induction of heme oxygenase-1, Front. Immunol., 2019, vol. 10, p. 345.

  15. Carr, A.C. and Cook, J., Intravenous vitamin C for cancer therapy—identifying the current gaps in our knowledge, Front. Physiol., 2018, vol. 9, p. 1182.

    PubMed  PubMed Central  Google Scholar 

  16. Castillo, J., Benavente-Garcia, O., Lorente, J., et al., Antioxidant activity and radioprotective effects against chromosomal damage induced in vivo by x-rays of flavan-3-ols (procyanidins) from grape seeds (Vitis vinifera): comparative study versus other phenolic and organic compounds, J. Agric. Food Chem., 2001, vol. 46, no. 5, pp. 738–1745.

    Google Scholar 

  17. Chang, K.M., Chen, H.H., Wang, T.C., et al., Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model, Eur. J. Med. Chem., 2015, vol. 106, pp. 60–74.

    CAS  PubMed  Google Scholar 

  18. Chatterjee, A., Reduced glutathione: a radioprotector or a modulator of DNA-repair activity? Nutrients, 2013, vol. 5, no. 2, pp. 525–542.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Chen, Q.M. and Maltagliati, A.J., Nrf2 at the heart of oxidative stress and cardiac protection, Physiol. Genomics, 2018, vol. 50, no. 2, pp. 77–97.

    CAS  PubMed  Google Scholar 

  20. Chertkov, K.S. and Petrov, V.M., Pharmacochemical protection and substitutive treatment as components of the radiation safety system of astronauts during an expedition to Mars, Aviakosm. Ekol. Med., 1993, vol. 27, nos. 5–6, pp. 27–32.

    Google Scholar 

  21. Chwee, J.Y., Khatoo, M., Tan, N.Y.J., and Gasser, S., Apoptotic cells release IL1 receptor antagonist in response to genotoxic stress, Cancer Immunol. Res., 2016, vol. 4, no. 4, pp. 294–302.

    CAS  PubMed  Google Scholar 

  22. Corbi, G., Conti, V., and Russomanno, G., Adrenergic signaling and oxidative stress: a role for sirtuins? Front. Physiol., 2013, vol. 4, p. 324.

    PubMed  PubMed Central  Google Scholar 

  23. Costa, L.G., Garrick, J.M., Roque, P.J., and Pellacani, C., Mechanisms of neuroprotection by quercetin: counteracting oxidative stress and more, Oxid. Med. Cell. Longevity, 2016, vol. 7, pp. 1–10.

    Google Scholar 

  24. Dinkova-Kostova, A.T. and Abramov, A.Y., The emerging role of Nrf2 in mitochondrial function, Free Radicals Biol. Med., 2015, vol. 88, part B, pp. 179–188.

  25. Epperly, M.W., Wang, H., Jones, J.A., et al., Antioxidant-chemoprevention diet ameliorates late effects of total-body irradiation and supplements radioprotection by MnSOD-plasmid liposome administration, Radiat. Res., 2011, vol. 175, no. 6, pp. 759–765.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Espada, S., Ortega, F., Molina-Jijon, E., et al., The purinergic P2Y13 receptor activates the Nrf2/HO-1 axis and protects against oxidative stress-induced neuronal death, Free Radicals Biol. Med., 2010, vol. 49, no. 3, pp. 416–442.

    CAS  Google Scholar 

  27. Fabre, G., Bayach, I., Berka, K., et al., Synergism of antioxidant action of vitamins E, C and quercetin is related to formation of molecular associations in biomembranes, Chem. Commun., 2015, vol. 51, no. 36, pp. 7713–7716.

    CAS  Google Scholar 

  28. Fan, Z.L., Wang, Z.Y., Zuo, L.L., and Tian, S.Q., Protective effect of anthocyanins from lingonberry on radiation-induced damages, Int. J. Environ. Res. Publ. Health, 2012, vol. 9, no. 12, pp. 4732–4743.

    Google Scholar 

  29. Ferdows, K., Hatami, H., and Dehghan, G., Investigation the protective effect of vitamin C on anxiety and oxidative stress modulation in male rats treated with progesterone, Trakia J. Sci., 2016, no. 2, pp. 115–125.

  30. Francescato, H.D., Coimbra, T.M., Costa, R.S., and de Bianchi, M.L., Protective effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis, Kidney Blood Pressure Res., 2004, vol. 27, pp. 148–158.

    CAS  Google Scholar 

  31. Fujii, M. and Hou, D., Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin, Free Radicals Biol. Med., 2007, vol. 42, pp. 1690–1703.

    Google Scholar 

  32. Fukushima, R. and Yamazaki, E., Vitamin C requirement in surgical patients, Curr. Opin. Clin. Nutr. Metab. Care, 2010, vol. 13, no. 6, pp. 669–676.

    CAS  PubMed  Google Scholar 

  33. Garkavi, L.Kh., Kvakina, E.B., and Ukolova, M.A., Adaptatsionnye reaktsii i rezistentnost’ organizma (Adaptive Reactions and Resistance of an Organism), Rostov-on-Don: Rostov. Gos. Univ., 1990.

  34. Go, Y.-M. and Jones, D.P., Thiol/disulfide redox states in signaling and sensing, Crit. Rev. Biochem. Mol. Biol., 2013, vol. 48, no. 2, pp. 173–181.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Grabowska, W., Sikora, E., and Bielak-Zmijewska, A., Sirtuins, a promising target in slowing down the ageing process, Biogerontology, 2017, vol. 18, no. 4, pp. 447–476.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Gudkov, S.V., Shtarkman, I.N., Smirnova, V.S., et al., Guanosine and inosine display antioxidant activity, protect DNA in vitro from oxidative damage induced by reactive oxygen species, and serve as radioprotectors in mice, Radiat. Res., 2006, vol. 165, no. 5, pp. 538–545.

    CAS  PubMed  Google Scholar 

  37. Gudkov, S.V., Gudkova, O.Y., Chernikov, V.A., and Bruskov, V.I., Protection of mice against X-ray injuries by the post-radiation administration of guanosine and inosine, Int. J. Radiat. Biol., 2009, vol. 85, no. 2, pp. 116–125.

    CAS  PubMed  Google Scholar 

  38. Gushcha, N.A., Perkovskaya, G.Yu., Dmitriev, A.P., and Grodzinskii, D.M., The effect of chronic radiation on the adaptive potential of the plants, Radiats. Biol., Radioekol., 2002, vol. 42, no. 2, pp. 155–158.

    CAS  Google Scholar 

  39. Haskins, A.H., Buglewicz, D.J., and Hirakawa, H., Palmitoyl ascorbic acid 2-glucoside has the potential to protect mammalian cells from high-LET carbon-ion radiation, Sci. Rep., 2018, vol. 8, pp. 13822.

    PubMed  PubMed Central  Google Scholar 

  40. Hung, C.H., Chan, S.H., Chu, P.M., and Tsai, K.L., Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation, Mol. Nutr. Food Res., 2015, vol. 59, no. 10, pp. 1905–1917.

    CAS  PubMed  Google Scholar 

  41. Ito, Y., Kinoshita, M., Yamamoto, T., et al., A combination of pre- and post-exposure ascorbic acid rescues mice from radiation-induced lethal gastrointestinal damage, Int. J. Mol. Sci., 2013, vol. 14, no. 10, pp. 19618–19635.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Ivanenko, G.F. and Burlakova, E.B., The effect of low dose ionizing radiation on the thiol disulfide system and lipid antioxidants in blood plasma, Radiats.Risk, 2017, vol. 26, no. 4, pp. 111–123.

    Google Scholar 

  43. Izzi, V., Masuelli, L., Tresoldi, I., et al., The effects of dietary flavonoids on the regulation of redox inflammatory networks, Front. Biosci., 2012, vol. 17, no. 7, pp. 2396–2418.

    Google Scholar 

  44. Jandaz, K.H., Saeed, S.A., and Gilani, A.H., Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents, Phytomedicine, 2004, vol. 11, pp. 424–430.

    Google Scholar 

  45. Janjua, N.K., Siddiqa, A., Yaqub, A., et al., Spectrophotometric analysis of flavonoid-DNA binding interactions at physiological conditions, Spectrochim. Acta, Part A, 2009, vol. 74, no. 5, pp. 1135–1137.

    Google Scholar 

  46. Jeong, Y.J., Choi, Y.J., and Kwon, H.M., Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids, Br. J. Nutr., 2005, vol. 93, no. 5, pp. 581–591.

    CAS  PubMed  Google Scholar 

  47. Jing, H. and Lin, H., Sirtuins in epigenetic regulation, Chem. Rev., 2015, vol. 115, no. 6, pp. 2350–2375.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kane, A.E. and Sinclair, D.A., Sirtuins and NAD+ in the development and treatment of metabolic and cardiovascular diseases, Circ. Res., 2018, vol. 123, pp. 868–885.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Kawabata, K., Kawai, Y., and Terao, J., Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats, J. Nutr. Biochem., 2010, vol. 21, no. 5, pp. 374–380.

    CAS  PubMed  Google Scholar 

  50. Kensler, T.W., Wakabayashi, N., and Biswal, S., Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway, Annu. Rev. Pharmacol. Toxicol., 2007, vol. 47, pp. 89–116.

    CAS  PubMed  Google Scholar 

  51. Kerimi, A. and Williamson, G., Differential impact of flavonoids on redox modulation, bioenergetics, and cell signaling in normal and tumor cells: a comprehensive review, Antioxid. Redox Signaling, 2018, vol. 29, no. 16, pp. 1633–1659.

    CAS  Google Scholar 

  52. Khor, T.O., Huang, Y., Wu, T.-Y., et al., Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation, Biochem. Pharmacol., 2011, vol. 82, pp. 1073–1078.

    CAS  PubMed  Google Scholar 

  53. Kobashigawa, S., Kashino, G., Mori, H., and Watanabe, M., Relief of delayed oxidative stress by ascorbic acid can suppress radiation-induced cellular senescence in mammalian fibroblast cells, Mech. Ageing Dev., 2015, vol. 146, pp. 65–71.

    PubMed  Google Scholar 

  54. Kumar, R.S., Narayanan, S.N., and Nayak, S., Ascorbic acid protects against restraint stress-induced memory deficits in Wistar rats, Clinics, 2009, vol. 64, no. 12, pp. 1211–1217.

    PubMed  PubMed Central  Google Scholar 

  55. Legeza, V.I., Abdul’, Yu.A., Antushevich, A.E., et al., The effect of riboxin on the resistance of mice to prolonged non-lethal gamma irradiation, Radiobiologiya, 1993, vol. 33, no. 5, pp. 658–664.

    CAS  Google Scholar 

  56. Lim, J.C., Choi, H.I., Park, Y.S., et al., Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity, J. Biol. Chem., 2008, vol. 283, no. 43, pp. 28873–28880.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Linard, C., Marquette, C., Mathieu, J., et al., Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: effect of an NF-κ B inhibitor, Int. J. Radiat. Oncol. Biol. Phys., 2004, vol. 58, no. 2, pp. 427–434.

    CAS  PubMed  Google Scholar 

  58. Ma, Q., Role of Nrf2 in oxidative stress and toxicity, Annu. Rev. Pharmacol. Toxicol., 2013, vol. 53, pp. 401–426.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Makarova, M.N., Makarov, V.G., and Zenkevich, I.G., Antiradical activity of flavonoids and their combinations with other antioxidants, Farmatsiya, 2004, no. 2, pp. 30–32.

  60. Mansuri, M.L., Parihar, P., Solanki, I., and Parihar, M.S., Flavonoids in modulation of cell survival signalling pathways, Genes Nutr., 2014, vol. 9, no. 3, p. 400.

    PubMed  PubMed Central  Google Scholar 

  61. Marina, R., Gonzalez, P., Ferreras, C., et al., Hepatic Nrf2 expression is altered by quercetin supplementation in x-irradiated rats, Mol. Med. Rep., 2015, vol. 11, pp. 539–546.

    CAS  PubMed  Google Scholar 

  62. Mathew, D., Nair, C.K., Jacob, J.A., et al., Ascorbic acid monoglucoside as antioxidant and radioprotector, J. Radiat. Res., 2007, vol. 48, no. 5, pp. 369–376.

    CAS  PubMed  Google Scholar 

  63. Mattson, M.P., Hormesis defined, Ageing Res. Rev., 2008, vol. 7, no. 1, pp. 1–7.

    CAS  PubMed  Google Scholar 

  64. Mattson, M.P., Duan, W., Chan, S.L., et al., Neuroprotective and neurorestorative signal transduction mechanisms in brain aging: modification by genes, diet and behavior, Neurobiol. Aging, 2002, vol. 23, pp. 695–705.

    CAS  PubMed  Google Scholar 

  65. Matzinger, M., Fischhuger, K., and Heiss, E.H., Activation of Nrf2 signaling by natural products-can it alleviate diabetes? Biotechnol. Adv., 2018, vol. 36, no. 6, pp. 1738–1767.

    CAS  PubMed  Google Scholar 

  66. Maurice, D., Lightsey, S.F., Toler, J.E., and Canty, S., Effect of chronic oxidative/corticosterone-induced stress on ascorbic acid metabolism and total antioxidant capacity in chickens (Gallus gallus domesticus), J. Anim. Physiol. Anim. Nutr., 2007, vol. 91, nos. 7–8, pp. 355–360.

    CAS  Google Scholar 

  67. Mayo, J.C., Sainz, R.M., González Menéndez, P., et al., Melatonin and sirtuins: a “not-so unexpected” relationship, J. Pineal Res., 2017, vol. 62, no. 2, pp. 1–17.

    Google Scholar 

  68. McDonald, J.T., Kim, K., Norris, A.J., et al., Ionizing radiation activates the Nrf2 antioxidant response, Cancer Res., 2010, vol. 70, no. 21, pp. 8886–8895.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Menendez, J.A., Joven, J., Aragones, G., et al., Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil: a new family of gerosuppressant agents, Cell Cycle, 2013, vol. 12, no. 4, pp. 555–578.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Meyers, K.J., Rudolf, J.L., and Mitchell, A.E., Influence of dietary quercetin on glutathione redox status in mice, J. Agric. Food Chem., 2008, vol. 56, no. 3, pp. 830–836.

    CAS  PubMed  Google Scholar 

  71. Montecinos, V., Guzmán, P., Barra, V., et al., Vitamin C is an essential antioxidant that enhances survival of oxidatively stressed human vascular endothelial cells in the presence of a vast molar excess of glutathione, J. Biol. Chem., 2007, vol. 282, pp. 15506–15515.

    CAS  PubMed  Google Scholar 

  72. Mortazavi, S.M.J., Rahimi, S., Mosleh-Shirazi, M.A., et al., A comparative study on the life-saving radioprotective effects of vitamins A, E, C and over-the-counter multivitamins, J. Biomed. Phys. Eng., 2015a, vol. 5, no. 2, pp. 59–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Mortazavi, S.M.J., Foadi, M., Mozdaran, H., et al., Future role of vitamin C in radiation mitigation and its possible applications in manned deep space missions: survival study and the measurement of cell viability, Int. J. Radiat. Res., 2015b, vol. 13, no. 1, pp. 55–60.

    Google Scholar 

  74. Najafi, M., Shirazi, A., Motevaseli, E., et al., The melatonin immunomodulatory actions in radiotherapy, Biophys. Rev., 2017, vol. 9, no. 2, pp. 139–148.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Nam, S., Smith, D.M., and Dou, Q.P., Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo, J. Biol. Chem., 2001, vol. 276, pp. 13322–13330.

    CAS  PubMed  Google Scholar 

  76. O’Callaghan, C. and Vassilopoulos, A., Sirtuins at the crossroads of stemness, aging, and cancer, Aging Cell, 2017, vol. 16, no. 6, pp. 1208–1218.

    PubMed  PubMed Central  Google Scholar 

  77. Orbeli, L.A., Adaptation-trophic role of the sympathetic nervous system and cerebellum, and higher nervous activity, Fiziol. Zh. SSSR im. I.M. Sechenova, 1949, vol. 35, no. 5, pp. 594–605.

    CAS  PubMed  Google Scholar 

  78. Paidi, M.D., Schjoldager, J.G., Lykkesfeldt, J., and Tveden, P., Chronic vitamin C deficiency promotes redox imbalance in the brain but does not alter sodium-dependent vitamin C transporter 2 expression, Nutrients, 2014, vol. 6, pp. 1809–1822.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Paital, B., Panda, S.K., Hati, A.K., et al., Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming, World J. Biol. Chem., 2016, vol. 7, no. 1, pp. 110–127.

    PubMed  PubMed Central  Google Scholar 

  80. Paraswani, N., Thoh, M., Bhilwade, H.N., and Ghosh, A., Early antioxidant responses via the concerted activation of NF-κB and Nrf2 characterize the gamma-radiation-induced adaptive response in quiescent human peripheral blood mononuclear cells, Mutat. Res., 2018, vol. 831, pp. 50–61.

    CAS  Google Scholar 

  81. Patak, P., Willenberg, H.S., and Bornstein, S.R., Vitamin C is an important cofactor for both adrenal cortex and adrenal medulla, Endocrinol. Res., 2004, vol. 30, no. 4, pp. 871–875.

    CAS  Google Scholar 

  82. Patil, S.L., Somashekarappa, H., and Rajashekhar, K., Radiomodulatory role of rutin and quercetin in Swiss albino mice exposed to the whole body gamma radiation, Indian J. Nucl. Med., 2012, vol. 27, no. 4, pp. 237–242.

    PubMed  PubMed Central  Google Scholar 

  83. Patil, S.L., Mallaiah, S.H., and Patil, R.K., Antioxidative and radioprotective potential of rutin and quercetin in Swiss albino mice exposed to gamma radiation, J. Phys. Med., 2013, vol. 38, no. 2, pp. 87–92.

    Google Scholar 

  84. Price, N.L., Gomes, A.P., Ling, A.J., et al., SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function, Cell Metab., 2012, vol. 15, no. 5, pp. 675–690.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Qiu, P., Dong, Y., Li, B., et al., Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap1/Nrf2 pathway to alleviate ethanol-induced hepatic injury, Toxicol. Lett., 2017, vol. 274, pp. 31–41.

    CAS  PubMed  Google Scholar 

  86. Qureshi, A.A., Guan, X.Q., Reis, J.C., et al., Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor, Lipids Health Dis., 2012, vol. 11, p. 76.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Rahnasto-Rilla, M., Tyni, J., Huovinen, M., et al., Natural polyphenols as sirtuin 6 modulators, Sci. Rep., 2018, vol. 8, p. 4163.

    PubMed  PubMed Central  Google Scholar 

  88. Redondo-Castro, E., Cunningham, C., Miller, J., et al., Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory and pro-trophic phenotype in vitro, Stem Cell Res. Ther., 2017, vol. 8, no. 1, pp. 79.

    PubMed  PubMed Central  Google Scholar 

  89. Rogozkin, V.D., Application of a vitamin–amino acid complex under proton irradiation at nonlethal doses, in Biologicheskoe deistvie protonov vysokikh energii (Biological Effects of High-Energy Protons), Moscow: Atomizdat, 1967, pp. 417–433.

  90. Rogozkin, V.D., Gvozdeva, N.I., Sbitneva, M.F., et al., The effect of aminotetravit and ATP on hematopoiesis in dogs after repeated exposure to chronic gamma radiation, Kosm. Biol. Med., 1971, vol. 5, no. 2, pp. 42–46.

    Google Scholar 

  91. Ruderman, N.B., Xu, X.J., Nelson, L., et al., AMPK and SIRT1: a long-standing partnership? Am. J. Physiol.: Endocrinol. Metab., 2010, vol. 298, no. 4, pp. e751–e760.

    CAS  Google Scholar 

  92. Saksonov, P.P., Protection against radiation (biological, pharmacological, chemical, and physical), in Foundation of Space Biology and Medicine, Saksonov, P.P., Ed., Washington, DC: Natl. Aeronaut. Space Admin., 1975, vol. 3, pp. 316–347.

    Google Scholar 

  93. Saksonov, P.P., Shashkov, V.S., and Sergeev, P.V., Radiatsionnaya farmakologiya (Radiation Pharmacology), Moscow: Meditsina, 1976.

  94. Salminen, A., Kaarniranta, K., and Kauppinen, A., Crosstalk between oxidative stress and SIRT1: impact on the aging process, Int. J. Mol. Sci., 2013, vol. 14, no. 2, pp. 3834–3859.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. SanPin 2.6.1.2523-09. Normy radiatsionnoi bezopasnosti NRB-99/2009 (SanPin 2.6.1.2523-09. Norms of Radiation Safety NRB-99/2009), Moscow, 2009.

  96. Santos, L., Escande, C., and Denicola, A., Potential modulation of sirtuins by oxidative stress, Oxid. Med. Cell. Longevity, 2016, vol. 12, pp. 1–12.

    Google Scholar 

  97. Sato, T., Kinoshita, M., Yamamoto, T., et al., Treatment of irradiated mice with high-dose ascorbic acid reduced lethality, PLoS One, 2015, vol. 10, no. 2, p. e0117020.

    PubMed  PubMed Central  Google Scholar 

  98. Satoh, A., Stein, L., and Imai, S., The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity, Handb. Exp. Pharmacol., 2011, vol. 206, pp. 125–162.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Schuitemaker, G.E., Vitamin C as protection against radiation exposure, J. Orthomol. Med., 2011, vol. 26, no. 3, pp. 141–145.

    Google Scholar 

  100. Sekhar, K.R. and Freeman, M.L., NRF2 promotes survival following exposure to ionizing radiation, Free Radicals Biol. Med., 2015, vol. 88, part B, pp. 268–274.

  101. Sharapov, M.G., Novoselov, V.I., and Gudkov, S.V., Radioprotective role of peroxiredoxin 6, Antioxidants, 2019, vol. 8, no. 1, p. e15.

    PubMed  Google Scholar 

  102. Shibamoto, Y. and Nakamura, H., Overview of biological, epidemiological, and clinical evidence of radiation hormesis, Int. J. Mol. Sci., 2018, vol. 19, no. 8, pp. 2387.

    PubMed Central  Google Scholar 

  103. Singh, V.K., Fatanmi, O.O., Singh, P.K., and Whitnall, M.H., Role of radiation-induced granulocyte colony-stimulating factor in recovery from whole body gamma-irradiation, Cytokine, 2012, vol. 58, no. 3, pp. 406–4014.

    CAS  PubMed  Google Scholar 

  104. Singh, C.K., Chhabra, G., Ndiaye, M.A., et al., The role of sirtuins in antioxidant and redox signaling, Antioxid. Redox Signaling, 2018, vol. 28, no. 8, pp. 643–661.

    CAS  Google Scholar 

  105. Smaaland, R., Svardal, A.M., Lote, K., et al., Glutathione content in human bone marrow and circadian stage relation to DNA synthesis, J. Natl. Cancer Inst., 1991, vol. 83, no. 15, pp. 1092–1098.

    CAS  PubMed  Google Scholar 

  106. Spadari, R.C., Cavadas, C., de Carvalho, A.E.T.S., et al., Role of beta-adrenergic receptors and sirtuin signaling in the heart during aging, heart failure, and adaptation to stress, Cell Mol. Neurobiol., 2018, vol. 38, no. 1, pp. 109–120.

    CAS  PubMed  Google Scholar 

  107. Stoecklein, V.M., Osuka, A., Ishikawa, S., et al., Radiation exposure induces inflammasome pathway activation in immune cells, J. Immunol., 2015, vol. 194, no. 3, pp. 178–1189.

    Google Scholar 

  108. Sun, Y., Yang, T., Leak, R.K., et al., Preventive and protective roles of dietary Nrf2 activators against central nervous system diseases, CNS Neurol. Disord.: Drug Targets, 2017, vol. 16, no. 3, pp. 326–338.

    CAS  Google Scholar 

  109. Tamari, Y., Nawata, H., Inoue, E., et al., Protective roles of ascorbic acid in oxidative stress induced by depletion of superoxide dismutase in vertebrate cells, Free Radicals Res., 2013, vol. 47, no. 1, pp. 1–7.

    CAS  Google Scholar 

  110. Tipton, C.M., Determinants of VO2 max: insights gained from non-human species, Acta Physiol. Scand. Suppl., 1986, vol. 556, pp. 33–43.

    CAS  PubMed  Google Scholar 

  111. Treviño-Saldaña, N. and García-Rivas, G., Regulation of sirtuin-mediated protein deacetylation by cardioprotective phytochemicals, Oxid. Med. Cell. Longevity, 2017, vol. 2017, art. ID 1750306.

    Google Scholar 

  112. Ullmann, K., Wiencierz, A.M., Müller, C., et al., A high-through-put reporter gene assay to prove the ability of natural compounds to modulate glutathione peroxidase, superoxide dismutase and catalase gene promoters in V79 cells, Free Radicals Res., 2008, vol. 42, no. 8, pp. 746–753.

    CAS  Google Scholar 

  113. Uma Devi, P., Ganasoundari, A., Vrinda, B., et al., Radiation protection by the Ocimum flavonoids orientin and vicenin: mechanisms of action, Radiat. Res., 2000, vol. 154, no. 4, pp. 455–460.

    CAS  PubMed  Google Scholar 

  114. Umegaki, K., Aoki, S., and Esashi, T., Whole body x-ray irradiation to mice decreases ascorbic acid concentration in bone marrow: comparison between ascorbic acid and vitamin E, Free Radicals Biol. Med., 1995, vol. 19, no. 4, pp. 493–197.

    CAS  Google Scholar 

  115. Ushakov, I.B. and Vasin, M.V., Radiation protective agents in the radiation safety system for long-term exploration missions, Hum. Physiol., 2014, vol. 40, no. 7, pp. 1–9.

    Google Scholar 

  116. Ushakov, I.B. and Vasin, M.V., Drugs and natural antioxidants as components of anti-radiation countermeasures in space flights, Med. Radiol. Radiats. Bezop., 2017, vol. 62, no. 4, pp. 66–78.

    Google Scholar 

  117. Ushakov, I.B. and Vasin, M.V., Pharmacological protection in distant space: modern view, Radiats. Biol., Radioekol., 2019, vol. 59, no. 2, pp. 150–160.

    Google Scholar 

  118. Vaiserman, A.M., Radiation hormesis: historical perspective and implications for low-dose cancer risk assessment, Dose-Response, 2010, vol. 8, no. 2, pp. 172–191.

    PubMed  PubMed Central  Google Scholar 

  119. van de Ven, R.A.H., Santos, D., and Haigis, M.C., Mitochondrial sirtuins and molecular mechanisms of aging, Trends Mol. Med., 2017, vol. 23, no. 4, pp. 320–331.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. van der Knaap, J.A. and Verrijzer, C.P., Undercover: gene control by metabolites and metabolic enzymes, Genes Dev., 2016, vol. 30, pp. 2345–2369.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Vasin, M.V., Protivoluchevye lekarstvennye sredstva (Antiradiation Medical Drugs), Moscow: Ross. Med. Akad. Poslediplomnogo Obraz., 2010.

  122. Vasin, M.V., Classification of antiradiation preparations as a reflection of modern state and development of radiation pharmacology, Radiats. Biol., Radioekol., 2013, vol. 53, no. 5, pp. 459–467.

    CAS  Google Scholar 

  123. Vasin, M.V. and Ushakov, I.B., The influence of ascorbic acid on acute toxicity and radioprotective properties of cystamine in experiments on small and large animals, Eksp. Klin. Farmakol., 2018, vol. 81, no. 8, pp. 23–25.

    CAS  Google Scholar 

  124. Vasin, M.V. and Ushakov, I.B., Potential ways to increase body resistance to damaging action of ionizing radiation with radiomitigators, Biol. Bull. Rev., 2019, vol. 9, no. 6, pp. 503–519.

    Google Scholar 

  125. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Comparative efficiency of antioxidant melatonin and radioprotectors indralin and phenylephrine in local radiation injuries, Radiats. Biol., Radioekol., 2004a, vol. 44, no. 1, pp. 68–71.

    CAS  Google Scholar 

  126. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Effect of melatonin, ascorbic acid, and succinic acid on the cumulative toxic effect of repeated treatment with gammafos (amifostine), Bull. Exp. Biol. Med., 2004b, vol. 137, no. 5, pp. 450–452.

    CAS  PubMed  Google Scholar 

  127. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., The effect of the combined use of quercetin and indralin on post-radiation recovery of the hematopoiesis system in acute radiation sickness, Radiats. Biol., Radioekol., 2011, vol. 51, no. 2, pp. 247–251.

    CAS  Google Scholar 

  128. Vasin, M.V., Kovtun, V.Yu., Komarova, S.N., et al., Combined effect of quercetin and indralin (B-190) in alleviating carboplatin hematologic toxicity, Vopr. Onkol., 2012, vol. 58, no. 1, pp. 77–80.

    CAS  PubMed  Google Scholar 

  129. Vasin, M.V., Ushakov, I.B., Kovtun, V.Yu., et al., Therapeutic effect of long-term melatonin treatment on the course and fatal outcome of modeled acute radiation sickness, Bull. Exp. Biol. Med., 2014, vol. 156, no. 6, pp. 776–777.

    CAS  PubMed  Google Scholar 

  130. Vasin, M.V., Solov’ev, V.Yu., Mal’tsev, V.N., et al., Primary radiation stress, inflammatory reaction and the mechanism of early postradiation reparative processes in irradiated tissues, Med. Radiol. Radiats. Bezop., 2018, vol. 63, no. 6, pp. 71–81.

    Google Scholar 

  131. Vazquez, B.N., Thackray, J.K., and Serrano, L., Sirtuins and DNA damage repair: SIRT7 comes to play, Nucleus, 2017, vol. 8, no. 2, pp. 107–115.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Venereau, E., Ceriotti, C., and Bianchi, M.E., DAMPs from cell death to new life, Front. Immunol., 2015, vol. 6, p. 422.

    PubMed  PubMed Central  Google Scholar 

  133. Vernarelli, J.A. and Lambert, J.D., Flavonoid intake is inversely associated with obesity and C-reactive protein, a marker for inflammation, in US adults, Nutr. Diabetes, 2017, vol. 7, no. 5, p. e276.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Vidhya, A. and Indira, M., Protective effect of quercitin in the regression of ethanol-incuced hepatotoxicity, Indian J. Pharm. Sci., 2009, vol. 71, pp. 527–532.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Vijayarghavan, R., Gautam, A., and Sharma, M., Comparative evaluation of some flavonoids and tocopherol acetate against the systemic toxicity induced by sulphur mustard, Indian J. Pharmacol., 2008, vol. 40, pp. 114–120.

    Google Scholar 

  136. Vriend, J. and Reiter, R.J., The Keap1-Nrf2-antioxidant response element pathway: a review of its regulation by melatonin and the proteasome, Mol. Cell Endocrinol., 2015, vol. 401, pp. 213–220.

    CAS  PubMed  Google Scholar 

  137. Wambi, C., Sanzari, J., Wan, X.S., et al., Dietary oxidants protect hematopoietic cells and improve animal survival after total-body irradiation, Radiat. Res., 2008, vol. 169, no. 4, pp. 384–396.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Weiss, J.F. and Landauer, M.R., Protection against ionizing radiation by antioxidant nutrients and phytochemicals, Toxicology, 2003, vol. 189, nos. 1–2, pp. 1–20.

    CAS  PubMed  Google Scholar 

  139. Woods, L.T., Ajit, D., Camden, J.M., et al., Purinergic receptors as potential therapeutic targets in Alzheimer’s disease, Neuropharmacology, 2016, vol. 104, pp. 169–179.

    CAS  PubMed  Google Scholar 

  140. Yamamoto, T., Kinoshita, M., Shinomiya, N., et al., Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation, J. Radiat. Res., 2010, vol. 51, no. 2, pp. 145–156.

    CAS  PubMed  Google Scholar 

  141. Yanagisawa, A., Iwata, M., and Akiyama, S., Effect of Vitamin C and Antioxidative Nutrition on Radiation-Induced Gene Expression in Fukushima Nuclear Plant Workers—A Pilot Study, Minato: Jpn. Coll. Intravenous Ther., 2012.

  142. Zendedel, E., Butler, A.E., Atkin, S.L., and Sahebkar, A., Impact of curcumin on sirtuins: a review, J. Cell Biochem., 2018, vol. 119, no. 12, pp. 10291–10300.

    CAS  PubMed  Google Scholar 

  143. Zhao, Y., Chen, B., Shen, J., et al., The beneficial effects of quercetin, curcumin, and resveratrol in obesity, Oxid. Med. Cell. Longevity, 2017, vol. 2017, art. ID 1459497.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. V. Vasin.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving animals and humans as subjects. All procedures performed in studies involving animals and humans were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Additional information

Translated by M. Batrukova

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vasin, M.V., Ushakov, I.B. Radiomodulators as Agents of Biological Protection against Oxidative Stress under the Influence of Ionizing Radiation. Biol Bull Rev 10, 251–265 (2020). https://doi.org/10.1134/S2079086420040106

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079086420040106

Keywords:

Navigation