Abstract

Radiotherapy, in addition to chemotherapy, is currently the primary method of cancer treatment based on destruction of malignant cells by ionizing radiation. Unfortunately, it also affects normal cells, which is associated with negative consequences for a patient. Radioprotectors are compounds used to prevent/protect the non-tumor cells from the harmful effects of radiation. To play their role these compounds should meet several criteria; among others, they should significantly protect normal cells from radiation without changing the tumor cell radiosensitivity. In general, agents used to alter normal tissue toxicity from radiation can be broadly divided into three categories based on timing of delivery in relation to radiation: chemical radioprotectors, mitigators, and treatment. These groups include a diverse range of synthetic compounds in terms of their structure and protective mechanisms. The aminoradiothiol amifostine is the only radioprotectant approved in clinical application. However, its use is limited due to toxicity concerns (it may cause hypotension). Natural compounds, derived from plants, meet all criteria of the ideal radioprotector. They exert their protective actions against adverse effects of ionizing radiation by several mechanisms. Plant compounds that show radioprotective activity include flavonoids and phenolic acids, stilbenes, lycopene, alkaloids, peptides, polysaccharides, and phytohormones. Garlic, green tea, apples, citrus, and ginger are examples of constituents of the human diet that contain radioprotective substances.

References

• 1. Akpolat M., Kanter M., Uzal M.C.: Protective effects of curcuminagainst g radiation-induced ileal mucosal damage. Arch. Toxicol.,2009; 83: 609-617
  Google Scholar
• 2. Ameri A., Heydarirad G., Rezaeizadeh H., Choopani R., GhobadiA., Gachkar L.: Evaluation of efficacy of an herbal compound on drymouth in patients with head and neck cancers: a randomized clinicaltrial. J. Evid. Based Complementary Altern. Med., 2016; 21: 30-33
  Google Scholar
• 3. Araujo M.C., Dias F.L., Takahashi C.S.: Potentiation by turmericand curcumin of g-radiation-induced chromosome aberrations inChinese hamster ovary cells. Teratog. Carcinog. Mutagen., 1999;19: 9-18
  Google Scholar
• 4. Arora R., Gupta D., Chawla R., Sagar R., Sharma A., Kumar R.,Prasad J., Singh S., Samanta N., Sharma R.K.: Radioprotection byplant products: present status and future prospects. Phytother. Res.,2005; 19: 1-22
  Google Scholar
• 5. Baliga M.S., Haniadka R., Pereira M.M., Thilakchand K.R., Rao S.,Arora R.: Radioprotective effects of Zingiber officinale Roscoe (ginger):past, present and future. Food Funct., 2012; 3: 714-723
  Google Scholar
• 6. Beskow C., Agren-Cronqvist A.K., Lewensohn R., Toma-Dasu I.:Biological effective dose evaluation and assessment of rectal andbladder complications for cervical cancer treated with radiotherapyand surgery. J. Contemp. Brachytherapy, 2012; 4: 205-212
  Google Scholar
• 7. Billen D.: Spontaneous DNA damage and its significance for the„negligible dose” controversy in radiation protection. Radiat. Res.,1990; 124: 242-245
  Google Scholar
• 8. Carsten R.E., Bachand A.M., Bailey S.M., Ullrich R.L.: Resveratrolreduces radiation-induced chromosome aberration frequencies inmouse bone marrow cells. Radiat. Res., 2008; 169: 633-638
  Google Scholar
• 9. Castillo J., Benavente-Garcia O., Lorente J., Alcaraz M., RedondoA., Ortuno A., Del Rio J.A.: Antioxidant activity and radioprotectivePismiennictwoeffects against chromosomal damage induced in vivo by X-rays offlavan-3-ols (Procyanidins) from grape seeds (Vitis vinifera): comparativestudy versus other phenolic and organic compounds. J. Agric.Food Chem., 2000; 48: 1738-1745
  Google Scholar
• 10. Citrin D., Cotrim A.P., Hyodo F., Baum B.J., Krishna M.C., MitchellJ.B.: Radioprotectors and mitigators of radiation-induced normaltissue injury. Oncologist, 2010; 15: 360-371
  Google Scholar
• 11. Das D., Sinha M., Khan A., Das K., Manna K., Dey S.: Radiationprotection by major tea polyphenol, epicatechin. Int. J. Hum. Genet.,2013; 13: 59-64
  Google Scholar
• 12. Davies M.J., Fu S., Wang H., Dean R.T.: Stable markers of oxidantdamage to proteins and their application in the study of human disease.Free Radic. Biol. Med., 1999; 27: 1151-1163
  Google Scholar
• 13. Ding J., Wang H., Wu Z.B., Zhao J., Zhang S., Li W.: Protectionof murine spermatogenesis against ionizing radiation-induced testicularinjury by a green tea polyphenol. Biol. Reprod., 2015; 92: 1-13
  Google Scholar
• 14. Dittmann K., Toulany M., Classen J., Heinrich V., Milas L., RodemannH.P.: Selective radioprotection of normal tissues by BowmanBirkproteinase inhibitor (BBI) in mice. Strahlenther. Onkol,, 2005;181: 191-196
  Google Scholar
• 15. Dobrzyński L.: Biologiczne skutki promieniowania jonizującego,Postępy Techniki Jądrowej, 2001; 44: 14-29
  Google Scholar
• 16. Finch P.W., Rubin J.S.: Keratinocyte growth factor/fibroblastgrowth factor 7, a homeostatic factor with therapeutic potential forepithelial protection and repair. Adv. Cancer Res., 2004; 91: 69-136
  Google Scholar
• 17. Giardi M.T., Touloupakis E., Bertolotto D., Mascetti G.: Preventiveor potential therapeutic value of nutraceuticals against ionizingradiation-induced oxidative stress in exposed subjects and frequentfliers. Int. J. Mol. Sci., 2013; 14: 17168-17192
  Google Scholar
• 18. Gloc E., Błasiak J.: Charakterystyka farmakologiczna i molekularnaamifostyny. J. Oncol., 2004; 54: 273-280
  Google Scholar
• 19. Guadagni F., Ferroni P., Palmirotta R., Del Monte G., Formica V.,Roselli M.: Non-steroidal anti-inflammatory drugs in cancer preventionand therapy. Anticancer. Res., 2007; 27: 3147-3162
  Google Scholar
• 20. Hakkim F.L., Miura M., Matsuda N., Alharassi A.S., Guillemin G.,Yamauchi M., Arivazhagan G., Song H.: An in vitro evidence for caffeicacid, rosmarinic acid and trans cinnamic acid as a skin protectantagainst γ-radiation. Int. J. Low Radiation, 2014; 9: 305-316
  Google Scholar
• 21. Haydont V., Bourgier C., Pocard M., Lusinchi A., Aigueperse J.,Mathé D., Bourhis J., Vozenin-Brotons M.C.: Pravastatin inhibits theRho/CCN2/extracellular matrix cascade in human fibrosis explantsand improves radiation-induced intestinal fibrosis in rats. Clin. CancerRes., 2007; 13: 5331-5340
  Google Scholar
• 22. Hayes J.D.; Kelleher M.O.; Eggelston I.M.: The cancer chemoprotectiveactions of phytochemicals derived from glucosinolates. Eur.J. Nutr., 2008; 47, Suppl. 2: 73-88
  Google Scholar
• 23. Headlam H.A., Davies M.J.: β-scission of side-chain alkoxyl radicalson peptides and proteins results in the loss of side-chains asaldehydes and ketones. Free Radic. Biol. Med., 2002; 32: 1171-1184
  Google Scholar
• 24. Hensley M.L., Hagerty K.L., Kewalramani T., Green D.M., MeropolN.J., Wasserman T.H., Cohen G.I., Emami B., Gradishar W.J., MitchellR.B., Thigpen J.T., Trotti A. 3rd, von Hoff D., Schuchter L.M.: AmericanSociety of Clinical Oncology 2008 clinical practice guidelineupdate: use of chemotherapy and radiation therapy protectants. J.Clin. Oncol., 2009; 27: 127-145
  Google Scholar
• 25. Hosseinimehr S.J.: Flavonoids and genomic instability inducedby ionizing radiation. Drug Discov. Today, 2010; 15: 907-918
  Google Scholar
• 26. Hosseinimehr S.J., Tavakoli H., Pourheidari G., Sobhani A.,Shafiee A.: Radioprotective effects of citrus extract against g-irradiationin mouse bone marrow cells. J. Radiat. Res, 2003; 44: 237-241
  Google Scholar
• 27. Jagetia G.C.: Radioprotective potential of plants and herbsagainst the effects of ionizing radiation. J.Clin. Biochem. Nutr.,2007; 40: 74-81
  Google Scholar
• 28. Jaiswal S.K., Bordia A.: Radio-protective effect of garlic Alliumsativum Linn. in albino rats. Indian J. Med. Sci., 1996; 50: 231-233
  Google Scholar
• 29. Karbownik M., Reiter R.J.: Antioxidative effects of melatoninin protection against cellular damage caused by ionizing radiation.Proc. Soc. Exp. Biol. Med., 2000; 225: 9-22
  Google Scholar
• 30. Kempner E.S.: Effects of high-energy electrons and g rays directlyon protein molecules. J. Pharm. Sci., 2001; 90: 1637-1646
  Google Scholar
• 31. Kim S.G., Nam S.Y., Kim C.W.: In vivo radioprotective effects ofoltipraz in g-irradiated mice. Biochem. Pharmacol., 1998; 55: 1585-1590
  Google Scholar
• 32. Knasmuller S., de Martin R., Domjan G., Szakmary A.: Studieson the antimutagenic activities of garlic extract. Environ. Mol. Mutagen.,1989, 13: 357-365
  Google Scholar
• 33. Konopacka M.: Niestabilność genetyczna i efekt sąsiedztwa indukowaneprzez promieniowanie jonizujące. J. Oncol., 2007; 57: 313-318
  Google Scholar
• 34. Koukourakis M.I.: Radiation damage and radioprotectants: newconcepts in the era of molecular medicine. Br. J. Radiol., 2012; 85:313-330
  Google Scholar
• 35. Krześlak A.: Kinaza Akt: kluczowy regulator metabolizmu i progresjinowotworów. Postępy Hig. Med. Dośw., 2010; 64: 490-503
  Google Scholar
• 36. Kumar S.S., Devasagayam T.P., Jayashree B., Kesavan P.C.: Mechanismof protection against radiation-induced DNA damage in plasmidpBR322 by caffeine. Int. J. Radiat. Biol., 2001; 77: 617-623
  Google Scholar
• 37. Kunnumakkara A.B., Diagaradjane P., Guha S., Deorukhkar A.,Shentu S., Aggarwal B.B., Krishnan S.: Curcumin sensitizes humancolorectal cancer xenografts in nude mice to g-radiation by targetingnuclear factor-κB-regulated gene products. Clin. Cancer Res.,2008; 14: 2128-2136
  Google Scholar
• 38. Landauer M.R., Srinivasan V., Seed T.M.: Genistein treatmentprotects mice from ionizing radiation injury. J. Appl. Toxicol., 2003;23: 379-385
  Google Scholar
• 39. Li J., Feng L., Xing Y., Wang Y., Du L., Xu C., Cao J., Wang Q., Fan S.,Liu Q., Fan F.: Radioprotective and antioxidant effect of resveratrol inhippocampus by activating sirt1. Int. J. Mol. Sci., 2014; 15: 5928-5939
  Google Scholar
• 40. Lombaert I.M., Brunsting J.F., Wierenga P.K., Kampinga H.H., deHaan G., Coppes R.P.: Keratinocyte growth factor prevents radiationdamage to salivary glands by expansion of the stem/progenitor pool.Stem Cells, 2008; 26: 2595-2601
  Google Scholar
• 41. Maurya D.K., Devasagayam T.P., Nair C.K.: Some novel approachesfor radioprotection and the beneficial effect of natural products.Indian J. Exp. Biol., 2006; 44: 93-114
  Google Scholar
• 42. Meyn R.E., Milas L., Ang K.K.: The role of apoptosis in radiationoncology. Int. J. Radiat. Biol., 2009; 85: 107-115
  Google Scholar
• 43. Moulder J.E., Cohen E.P.: Future strategies for mitigation andtreatment of chronic radiation-induced normal tissue injury. Semin.Radiat. Oncol., 2007; 17: 141-148
  Google Scholar
• 44. Moulder J.E., Fish B.L., Cohen E.P., Bonsib S.M.: Angiotensin IIreceptor antagonists in the prevention of radiation nephropathy.Radiat. Res., 1996; 146: 106-110
  Google Scholar
• 45. Nair C.K., Parida D.K., Nomura T.: Radioprotectors in radiotherapy.J. Radiat. Res., 2001; 42: 21-37
  Google Scholar
• 46. Nair G.G., Nair C.K.: Radioprotective effects of gallic acid in mice.Biomed Res. Int., 2013, 2013: 953079
  Google Scholar
• 47. O’Neill P., Wardman P.: Radiation chemistry comes before radiationbiology. Int. J. Radiat. Biol., 2009; 85: 9-25
  Google Scholar
• 48. Ostadhadi S., Rahmatollahi M., Dehpour A.R., Rahimian R.: Therapeuticpotential of cannabinoids in counteracting chemotherapy-inducedadverse effects: an exploratory review. Phytother. Res.,2015; 29: 332-338
  Google Scholar
• 49. Oszmiański J., Lamer-Zarawska E.: Substancje naturalne w profilaktycechorób nowotworowych. Wiad. Ziel., 1996; 38: 9-11
  Google Scholar
• 50. Palatty P.L., Azmidah A., Rao S., Jayachander D., ThilakchandK.R., Rai M.P., Haniadka R., Simon P., Ravi R., Jimmy R., D’souza P.F.,Fayad R., Baliga M.S.: Topical application of a sandal wood oil andturmeric based cream prevents radiodermatitis in head and neckcancer patients undergoing external beam radiotherapy: a pilotstudy. Br. J. Radiol., 2014; 87: 20130490
  Google Scholar
• 51. Parshad R., Sanford K.K., Price F.M., Steele V.E., Tarone R.E.,Kelloff G.J., Boone C.W.: Protective action of plant polyphenols onradiation-induced chromatid breaks in cultured human cells. AnticancerRes., 1998; 18: 3263-3266
  Google Scholar
• 52. Raviraj J., Bokkasam V.K., Kumar V.S., Reddy U.S., Suman V.:Radiosensitizers, radioprotectros, and radiation mitigators. IndianJ. Dent. Res., 2014; 25: 83-90
  Google Scholar
• 53. Reagan-Shaw S., Mukhtar H., Ahmad N.: Resveratrol impartsphotoprotection of normal cells and enhances the efficacy of radiationtherapy in cancer cells. Photochem. Photobiol., 2008; 84: 415-421
  Google Scholar
• 54. Reiter R.J., Tan D.X.: Melatonin: an antioxidant in edible plants.Ann. N.Y. Acad. Sci., 2002; 957: 341-344
  Google Scholar
• 55. Roszkowski K., Błaszczyk P.: Oksydacyjne uszkodzenia DNA jakopotencjalne markery skuteczności radioterapii. Wspolczesna Onkol.,2009; 13: 125-128
  Google Scholar
• 56. Roszkowski K., Foksiński M.: Wpływ promieniowaniajonizującego na DNA komórki. Wspolczesna Onkol., 2005; 9: 284-286
  Google Scholar
• 57. Ryan J.L.: Ionizing radiation: the good, the bad, and the ugly. J.Invest. Dermatol., 2012; 132: 985-993
  Google Scholar
• 58. Sauvaget C., Kasagi F., Waldren C.A.: Dietary factors and cancermortality among atomic bomb survivors. Mutat. Res., 2004; 551:145-152
  Google Scholar
• 59. Shimoi, K., Masuda S., Furugori M., Esaki S., Kinae N.: Radioprotectiveeffect of antioxidative flavonoids in g-ray irradiated mice.Carcinogenesis, 1994; 15: 2669-2672
  Google Scholar
• 60. Singh S.P., Abraham S.K., Kesavan P.C.: In vivo radioprotectionwith garlic extract. Mutat. Res.,1995; 345: 147-153
  Google Scholar
• 61. Sminia P., Kuipers G., Geldof A., Lafleur V., Slotman B.: COX-2inhibitors act as radiosensitizer in tumor treatment. Biomed. Pharmacother.,2005; 59: S272-S275
  Google Scholar
• 62. Spitz D.R., Azzam E.I., Li J.J., Gius D.: Metabolic oxidation/reductionreactions and cellular responses to ionizing radiation: A unifyingconcept in stress response biology. Cancer Metastasis Rev.,2004; 23: 311-322
  Google Scholar
• 63. Stalińska L., Ferenc T.: Rola TGF-β w regulacji cyklu komórkowego.Postępy Hig. Med. Dośw., 2005; 59: 441-449
  Google Scholar
• 64. Stefanelli A., Forte L., Medoro S., Sgualdo A., Lombardo D., ZiniG., Maronta D., Rainieri E., Pascale G., Bagnolatti P., Colella M., PrincivalleS., Fiorica F.: Topical use of phytotherapic cream (Capilen®cream) to prevent radiodermatitis in breast cancer: a prospectivehistorically controlled clinical study. G. Ital. Dermatol. Venereol.,2014; 149: 107-113
  Google Scholar
• 65. Swanson G.P., Jones W.E., Ha C.S., Jenkins C.A., Kumar A.P., BaslerJ:. Tolerance of Phellodendron amurense bark extract (Nexrutine®) inpatients with human prostate cancer. Phytother. Res., 2015; 29: 40-42
  Google Scholar
• 66. Tawfik S.S., Abouelella A.M., Shahein Y.E.: Curcumin protectionactivities against γ-Rays-induced molecular and biochemical lesions.B.M.C. Res. Notes, 2013; 6: 375
  Google Scholar
• 67. Uma Devi P., Agrawala Paban K.: Normal tissue protectorsagainst radiation injury. Defence Sci. J., 2011; 61:105-112
  Google Scholar
• 68. Uma Devi P., Ganasoundari A., Rao B.S., Srinivasan K.K.: In vivoradioprotection by ocimum flavonoids: survival of mice. Radiat.Res., 1999; 151: 74-78
  Google Scholar
• 69. Venkatachalam S.R., Chattopadhyay S.: Natural radioprotectiveagents: an overview. Curr. Org. Chem., 2005; 9: 389-404
  Google Scholar
• 70. Vijayalaxmi M., Meltz L., Reiter R.J., Herman T.S., Kumar K.S.:Melatonin and protection from whole-body irradiation: survivalstudies in mice. Mutat. Res., 1999; 425: 21-27
  Google Scholar
• 71. Wang J., Boerma M., Fu Q., Kulkarni A., Fink L.M., Hauer-JensenM.: Simvastatin ameliorates radiation enteropathy developmentafter localized, fractionated irradiation by a protein C-independentmechanism. Int. J. Radiat. Oncol. Biol. Phys., 2007; 68: 1483-1490
  Google Scholar
• 72. Williams J.P., Hernady E., Johnston C.J., Reed C.M., Fenton B.,Okunieff P., Finkelstein J.N.: Effect of administration of lovastatin onthe development of late pulmonary effects after whole-lung irradiationin a murine model. Radiat. Res., 2004; 161: 560-567
  Google Scholar
• 73. Wolski T., Baj T., Ludwiczuk A., Sałata M., Głowniak K.: Surowceroślinne o działaniu adaptogennym oraz ocena zawartości adaptogenóww ekstraktach i preparatach otrzymanych z rodzaju Panax.Post. Fitoter., 2009; 2: 77-97
  Google Scholar
• 74. Yeoh A., Gibson R., Yeoh E., Bowen J., Stringer A., Giam K., LoganR., Keefe D.: Radiation therapy-induced mucositis: Relationshipsbetween fractionated radiation, NF-κB, COX-1, and COX-2. CancerTreat. Rev., 2006; 32: 645-651
  Google Scholar
• 75. Zhu W., Xu J., Ge Y., Cao H., Ge X., Luo J., Xue J., Yang H., ZhangS., Cao J.: Epigallocatechin-3-gallate (EGCG) protects skin cells fromionizing radiation via heme oxygenase-1 (HO-1) overexpression. J.Radiat. Res., 2014; 55: 1056-1065
  Google Scholar

Full text