The melatonin immunomodulatory actions in radiotherapy

Biophysical Reviews

Volumn 9, Issue 2, 2017, Pages 139-148

  Najafi, M ^a   Shirazi, A ^a   Motevaseli, E ^a   Geraily, Gh ^a   Norouzi, F ^b   Heidari, M ^a   Rezapoor, S ^a  

^a TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b ISLAMIC AZAD UNIVERSITY   (Iran)

Author keywords

Cancer; Immune system; Melatonin; Radiation; Radiotherapy

Indexed keywords

CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYTOKINE; GAMMA INTERFERON; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; GLUTATHIONE TRANSFERASE; HIGH MOBILITY GROUP B1 PROTEIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 2; INTERLEUKIN 6; MELATONIN; PROTEIN KINASE; REACTIVE OXYGEN METABOLITE; RETINOID RELATED ORPHAN RECEPTOR ALPHA; TRANSCRIPTION FACTOR; TUMOR NECROSIS FACTOR; VASCULOTROPIN;

ANGIOGENESIS; APOPTOSIS; ATROPHY; BLOOD VESSEL INJURY; CELL DIFFERENTIATION; CELL GROWTH; DNA REPAIR; FIBROSIS; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOMODULATION; IONIZING RADIATION; NATURAL KILLER CELL; OXIDATIVE STRESS; PRIORITY JOURNAL; RADIOTHERAPY; REGULATORY T LYMPHOCYTE; REVIEW; TUMOR GROWTH;

EID: 85016935344     PISSN: 18672450     EISSN: 18672469     Source Type: Journal    
DOI: 10.1007/s12551-017-0256-8     Document Type: Review

References (130)

1. Amundson SA (2008) Functional genomics and a new era in radiation biology and oncology. Bioscience 58(6):491–500
2. Aydogan S, Yerer MB, Goktas A (2006) Melatonin and nitric oxide. J Endocrinol Investig 29(3):281–287
3. Behr TM, Sgouros G, Stabin MG, Béhé M, Angerstein C, Blumenthal RD et al (1999) Studies on the red marrow dosimetry in radioimmunotherapy: an experimental investigation of factors influencing the radiation-induced myelotoxicity in therapy with β-, Auger/conversion electron-, or α-emitters. Clin Cancer Res 5(10):3031s–3043s
4. Bentzen SM (2006) Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer 6(9):702–713
5. Bondy SC, Lahiri DK, Perreau VM, Sharman KZ, Campbell A, Zhou J et al (2004) Retardation of brain aging by chronic treatment with melatonin. Ann N Y Acad Sci 1035(1):197–215
6. Bower JE, Ganz PA, Aziz N, Fahey JL (2002) Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 64(4):604–611
7. Bower JE, Ganz PA, Tao ML, Hu W, Belin TR, Sepah S et al (2009) Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin Cancer Res 15(17):5534–5540
8. Brush J, Lipnick SL, Phillips T, Sitko J, McDonald JT, McBride WH (eds) (2007) Molecular mechanisms of late normal tissue injury. Seminars in radiation oncology. Elsevier
9. Caballero B, Vega‐Naredo I, Sierra V, Huidobro‐Fernández C, Soria‐Valles C, Gonzalo‐Calvo D et al (2009) Melatonin alters cell death processes in response to age‐related oxidative stress in the brain of senescence‐accelerated mice. J Pineal Res 46(1):106–114
10. Cagnoli CM, Atabay C, Kharlamova E, Manev H (1995) Melatonin protects neurons from singlet oxygen-induced apoptosis. J Pineal Res 18(4):222–226
11. Cakmak Karaer I, Simsek G, Yildiz A, Vardi N, Polat A, Tanbek K et al (2016) Melatonin’s protective effect on the salivary gland against ionized radiation damage in rats. J Oral Pathol Med 45(6):444–449
12. Calveley VL, Khan MA, Yeung IW, Vandyk J, Hill RP (2005) Partial volume rat lung irradiation: temporal fluctuations of in-field and out-of-field DNA damage and inflammatory cytokines following irradiation. Int J Radiat Biol 81(12):887–899
13. Canyilmaz E, Uslu GH, Bahat Z, Kandaz M, Mungan S, Haciislamoglu E et al (2016) Comparison of the effects of melatonin and genistein on radiation-induced nephrotoxicity: Results of an experimental study. Biomed Rep 4(1):45–50
14. Carrillo-Vico A, Reiter RJ, Lardone PJ, Herrera JL, Fernández-Montesinos R, Guerrero JM et al (2006) The modulatory role of melatonin on immune responsiveness. Curr Opin Investig Drugs 7(5):423
15. Chávez E, Reyes‐Gordillo K, Segovia J, Shibayama M, Tsutsumi V, Vergara P et al (2008) Resveratrol prevents fibrosis, NF‐κB activation and TGF‐β increases induced by chronic CCl4 treatment in rats. J Appl Toxicol 28(1):35–43
16. Chetsawang B, Putthaprasart C, Phansuwan-Pujito P, Govitrapong P (2006) Melatonin protects against hydrogen peroxide-induced cell death signaling in SH-SY5Y cultured cells: involvement of nuclear factor kappa B, Bax and Bcl-2. J Pineal Res 41(2):116–123
17. Cho SY, Lee HJ, Jeong SJ, Lee HJ, Kim HS, Chen CY et al (2011) Sphingosine kinase 1 pathway is involved in melatonin‐induced HIF‐1α inactivation in hypoxic PC‐3 prostate cancer cells. J Pineal Res 51(1):87–93
18. Choi YW, Munden RF, Erasmus JJ, Joo Park K, Chung WK, Jeon SC et al (2004) Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis 1. Radiographics 24(4):985–997
19. Choi EY, Jin JY, Lee JY, Choi JI, Choi IS, Kim SJ (2011) Melatonin inhibits Prevotella intermedia lipopolysaccharide‐induced production of nitric oxide and interleukin‐6 in murine macrophages by suppressing NF‐κB and STAT1 activity. J Pineal Res 50(2):197–206
20. Christopher FL, Dussault I, Miller SC (1991) Population dynamics of natural killer cells in the spleen and bone marrow of normal and leukemic mice during in vivo exposure to interleukin-2. Immunobiology 184(1):37–52
21. Cos S, Blask DE (1994) Melatonin modulates growth factor activity in MCF‐7 human breast cancer cells. J Pineal Res 17(1):25–32
22. Cucina A, Proietti S, D’Anselmi F, Coluccia P, Dinicola S, Frati L et al (2009) Evidence for a biphasic apoptotic pathway induced by melatonin in MCF‐7 breast cancer cells. J Pineal Res 46(2):172–180
23. Currier NL, Miller SC (2001) Echinacea purpurea and melatonin augment natural-killer cells in leukemic mice and prolong life span. J Altern Complement Med (New York, NY) 7(3):241–251
24. Currier NL, Sun L-Y, Miller SC (2000) Exogenous melatonin: quantitative enhancement in vivo of cells mediating non-specific immunity. J Neuroimmunol 104(2):101–108
25. Cuzzocrea S, Zingarelli B, Gilad E, Hake P, Salzman AL, Szabo C (1997) Protective effect of melatonin in carrageenan‐induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity. J Pineal Res 23(2):106–116
26. Cuzzocrea S, Costantino G, Mazzon E, Caputi AP (1999) Regulation of prostaglandin production in carrageenan‐induced pleurisy melatonin. J Pineal Res 27(1):9–14
27. Deng W-G, Tang S-T, Tseng H-P, Wu KK (2006) Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding. Blood 108(2):518–524
28. Di Bella G, Mascia F, Gualano L, Di Bella L (2013) Melatonin anticancer effects: review. Int J Mol Sci 14(2):2410–2430
29. Di Maggio FM, Minafra L, Forte GI, Cammarata FP, Lio D, Messa C et al (2015) Portrait of inflammatory response to ionizing radiation treatment. J Inflamm 12(1):14
30. Dragicevic N, Copes N, O’Neal‐Moffitt G, Jin J, Buzzeo R, Mamcarz M et al (2011) Melatonin treatment restores mitochondrial function in Alzheimer’s mice: a mitochondrial protective role of melatonin membrane receptor signaling. J Pineal Res 51(1):75–86
31. Emerit I, Oganesian N, Sarkisian T, Arutyunyan R, Pogosian A, Asrian K et al (1995) Clastogenic factors in the plasma of Chernobyl accident recovery workers: anticlastogenic effect of Ginkgo biloba extract. Radiat Res 144(2):198–205
32. Fardid R, Salajegheh A, Mosleh-Shirazi MA, Sharifzadeh S, Okhovat MA, Najafi M, Rezaeyan A, Abaszadeh A (2017) Melatonin ameliorates the production of COX-2, iNOS, and the formation of 8-OHdG in non-targeted lung tissue after pelvic irradiation. Cell J 19(2):324-331. doi:10.22074/cellj.2016.3857
33. García JA, Volt H, Venegas C, Doerrier C, Escames G, López LC et al (2015) Disruption of the NF-κB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-α and blocks the septic response in mice. FASEB J 29(9):3863–3875
34. Garcia-Maurino S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R et al (1997) Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol 159(2):574–581
35. García‐Mauriño S, Pozo D, Calvo JR, Guerrero JM (2000) Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines. J Pineal Res 29(3):129–137
36. Garcı́a-Pergañeda A, Guerrero JM, Rafii-El-Idrissi M, Romero MP, Pozo D, Calvo JR (1999) Characterization of membrane melatonin receptor in mouse peritoneal macrophages: inhibition of adenylyl cyclase by a pertussis toxin-sensitive G protein. J Neuroimmunol 95(1):85–94
37. Golden EB, Apetoh L (eds) (2015) Radiotherapy and immunogenic cell death. Seminars in radiation oncology. Elsevier
38. Golden E, Pellicciotta I, Demaria S, Barcellos-Hoff MH, Formenti SC (2012) The convergence of radiation and immunogenic cell death signaling pathways. Front Oncol 2:88
39. Green DR, Ferguson T, Zitvogel L, Kroemer G (2009) Immunogenic and tolerogenic cell death. Nat Rev Immunol 9(5):353–363
40. Gürses İ, Özeren M, Serin M, Yücel N, Erkal HŞ (2014) Histopathological evaluation of melatonin as a protective agent in heart injury induced by radiation in a rat model. Pathol Res Pract 210(12):863–871
41. Haddadi GH, Shirazi AR, Sepehrizadeh Z, Mahdavi SR, Haddadi M (2013) Radioprotective effect of melatonin on the cervical spinal cord in irradiated rats. Cell J 14(4):246–253
42. Harris JW, Phillips TL (1971) Radiobiological and biochemical studies of thiophosphate radioprotective compounds related to cysteamine. Radiat Res 46(2):362–379
43. Hashimoto S, Shirato H, Hosokawa M, Nishioka T, Kuramitsu Y, Matushita K et al (1999) The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats. Radiat Res 151(6):717–724
44. Hayashi T, Morishita Y, Kubo Y, Kusunoki Y, Hayashi I, Kasagi F et al (2005) Long-term effects of radiation dose on inflammatory markers in atomic bomb survivors. Am J Med 118(1):83–86
45. Haddadi GH, Rezaeyan A, Mosleh-Shirazi MA, Hosseinzadeh M, Fardid R, Najafi M, et al (2017) Hesperidin as radioprotector against radiation-induced lung damage in rat: A histopathological study. J Med Phys 42:25–32
46. Heylmann D, Rödel F, Kindler T, Kaina B (2014) Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells. Biochim Biophys Acta Rev Cancer 1846(1):121–129
47. Hong Y, Won J, Lee Y, Lee S, Park K, Chang KT et al (2014) Melatonin treatment induces interplay of apoptosis, autophagy, and senescence in human colorectal cancer cells. J Pineal Res 56(3):264–274
48. Jang SS, Kim HG, Lee JS, Han JM, Park HJ, Huh GJ et al (2013) Melatonin reduces X-ray radiation-induced lung injury in mice by modulating oxidative stress and cytokine expression. Int J Radiat Biol 89(2):97–105
49. Jardim BV, Ferreira LC, Borin TF, Moschetta MG, Gelaleti GB, Lopes JR et al (eds) (2013) Evaluation of the anti-angiogenic action of melatonin in breast cancer. BMC Proceedings, BioMed Central
50. Jardim-Perassi BV, Arbab AS, Ferreira LC, Borin TF, Varma NR, Iskander AS et al (2014) Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer. PLoS One 9(1):e85311
51. Joo SS, Yoo YM (2009) Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: therapeutic implications for prostate cancer. J Pineal Res 47(1):8–14
52. Kang JW, Lee SM (2012) Melatonin inhibits type 1 interferon signaling of toll‐like receptor 4 via heme oxygenase‐1 induction in hepatic ischemia/reperfusion. J Pineal Res 53(1):67–76
53. Karslioğlu I, Ertekin MV, Taysi S, Koçer I, Sezen O, Gepdiremen A et al (2005) Radioprotective effects of melatonin on radiation-induced cataract. J Radiat Res 46(2):277–282
54. Kaur C, Ling EA (1999) Effects of melatonin on macrophages/microglia in postnatal rat brain. J Pineal Res 26(3):158–168
55. Kiefer W, Dannhardt G (2002) COX-2 inhibition and the control of pain. Curr Opin Investig Drugs (London, England: 2000) 3(9):1348–1358
56. Kireev RA, Tresguerres AC, Castillo C, Salazar V, Ariznavarreta C, Vara E et al (2007) Effect of exogenous administration of melatonin and growth hormone on pro‐antioxidant functions of the liver in aging male rats. J Pineal Res 42(1):64–70
57. Kleszczyński K, Zillikens D, Fischer TW (2016) Melatonin enhances mitochondrial ATP synthesis, reduces reactive oxygen species formation, and mediates translocation of the nuclear erythroid 2‐related factor 2 resulting in activation of phase‐2 antioxidant enzymes (γ‐GCS, HO‐1, NQO1) in ultraviolet radiation‐treated normal human epidermal keratinocytes (NHEK). J Pineal Res 61(2):187–197
58. Kohchi C, Inagawa H, Nishizawa T, Soma G-I (2009) ROS and innate immunity. Anticancer Res 29(3):817–821
59. Korkmaz A, Reiter RJ, Topal T, Manchester LC, Oter S, Tan D-X (2009) Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med 15(1–2):43–50
60. Kotler M, Rodríguez C, Sáinz RM, Antolin I, Menéndez‐Peláez A (1998) Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J Pineal Res 24(2):83–89
61. Kusunoki Y, Hayashi T (2008) Long-lasting alterations of the immune system by ionizing radiation exposure: implications for disease development among atomic bomb survivors. Int J Radiat Biol 84(1):1–14
62. Kusunoki Y, Yamaoka M, Kubo Y, Hayashi T, Kasagi F, Douple EB et al (2010) T-cell immunosenescence and inflammatory response in atomic bomb survivors. Radiat Res 174(6b):870–876
63. Leach JK, Van Tuyle G, Lin P-S, Schmidt-Ullrich R, Mikkelsen RB (2001) Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res 61(10):3894–3901
64. León J, Casado J, Jiménez Ruiz SM, Zurita MS, González‐Puga C, Rejón JD et al (2014) Melatonin reduces endothelin‐1 expression and secretion in colon cancer cells through the inactivation of FoxO‐1 and NF‐κβ. J Pineal Res 56(4):415–426
65. Lezoualc’h F, Sparapani M, Behl C (1998) N‐acetyl‐serotonin (normelatonin) and melatonin protect neurons against oxidative challenges and suppress the activity of the transcription factor NF‐κB. J Pineal Res 24(3):168–178
66. Li W, Fan M, Chen Y, Zhao Q, Song C, Yan Y et al (2015) Melatonin induces cell apoptosis in AGS cells through the activation of JNK and P38 MAPK and the suppression of nuclear factor-kappa B: a novel therapeutic implication for gastric cancer. Cell Physiol Biochem 37(6):2323–2338
67. Linard C, Marquette C, Mathieu J, Pennequin A, Clarençon D, Mathé D (2004) Acute induction of inflammatory cytokine expression after γ-irradiation in the rat: effect of an NF-κB inhibitor. Int J Radiat Oncol Biol Phys 58(2):427–434
68. Lissoni P, Rovelli F, Malugani F, Bucovec R, Conti A, Maestroni GJ (2001) Anti-angiogenic activity of melatonin in advanced cancer patients. Neuroendocrinol Lett 22(1):45–48
69. Liu H, Xu L, Wei JE, Xie MR, Wang SE, Zhou RX (2011) Role of CD4+ CD25+ regulatory T cells in melatonin‐mediated inhibition of murine gastric cancer cell growth in vivo and in vitro. Anat Rec 294(5):781–788
70. Lorimore SA, Coates PJ, Scobie GE, Milne G, Wright EG (2001) Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects? Oncogene 20(48):7085–7095
71. Luchetti F, Betti M, Canonico B, Arcangeletti M, Ferri P, Galli F et al (2009) ERK MAPK activation mediates the antiapoptotic signaling of melatonin in UVB-stressed U937 cells. Free Radic Biol Med 46(3):339–351
72. Maestroni GJ (1995) T‐Helper‐2 lymphocytes as a peripheral target of melatonin. J Pineal Res 18(2):84–89
73. Manchester LC, Coto‐Montes A, Boga JA, Andersen LPH, Zhou Z, Galano A et al (2015) Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J Pineal Res 59(4):403–419
74. Mayo JC, Sainz RM, Tan D-X, Hardeland R, Leon J, Rodriguez C et al (2005) Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J Neuroimmunol 165(1):139–149
75. Meltz ML, Reiter RJ, Herman TS (1999) Melatonin and protection from genetic damage in blood and bone marrow: Whole‐body irradiation studies in mice. J Pineal Res 27(4):221–225
76. Michaeloudes C, Sukkar MB, Khorasani NM, Bhavsar PK, Chung KF (2011) TGF-β regulates Nox4, MnSOD and catalase expression, and IL-6 release in airway smooth muscle cells. Am J Phys Lung Cell Mol Phys 300(2):L295–L304
77. Mihandoust E, Shirazi A (2010) Application of radioprotective agents in cancer treatment. Iran J Nucl Med 18(1):107–107
78. Mohan N, Sadeghi K, Reiter RJ, Meltz ML (1995) The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B. Biochem Mol Biol Int 37(6):1063–1070
79. Muralidharan S, Mandrekar P (2013) Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol 94(6):1167–1184
80. Najafi M, Fardid R, Hadadi Gh, Fardid M (2014) The Mechanisms of Radiation-Induced Bystander Effect. J Biomed Phys Eng 4(4):163-172.
81. Najafi M, Fardid R, Takhshid MA, Mosleh-Shirazi MA, Rezaeyan AH, Salajegheh A (2016) Radiation-induced oxidative stress at out-of-field lung tissues after pelvis irradiation in rats. Cell J 18(3):340–345
82. Najafi M, Salajegheh A, Rezaeyan A (2017a) Bystander effect and second primary cancers following radiotherapy: What are its significances?. J Med Phys 42:55–56
83. Najafi M, Shirazi A, Motevaseli E, Rezaeyan AH, Salajegheh A, Rezapoor S (2017b) Melatonin as an anti-inflammatory agent in radiotherapy. Inflammopharmacology. doi:10.1007/s10787-017-0332-5
84. Ortiz F, Acuña‐Castroviejo D, Doerrier C, Dayoub JC, López LC, Venegas C et al (2015) Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation‐induced oral mucositis. J Pineal Res 58(1):34–49
85. Park SY, Jang WJ, Yi EY, Jang JY, Jung Y, Jeong JW et al (2010) Melatonin suppresses tumor angiogenesis by inhibiting HIF‐1α stabilization under hypoxia. J Pineal Res 48(2):178–184
86. Perrone G, Ruffini PA, Catalano V, Spino C, Santini D, Muretto P et al (2008) Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer. Eur J Cancer (Oxford, England: 1990) 44(13):1875–1882
87. Persson HL, Kurz T, Eaton JW, Brunk UT (2005) Radiation-induced cell death: importance of lysosomal destabilization. Biochem J 389(3):877–884
88. Pockley AG (2012) Radiation-induced effects and the immune system in cancer. Radiat Induc Eff Immune Syst. 121
89. Poon AM, Liu ZM, Pang CS, Brown GM, Pang SF (1994) Evidence for a direct action of melatonin on the immune system. Biol Signals 3(2):107–117
90. Pozo D, Reiter RJ, Calvo JR, Guerrero JM (1994) Physiological concentrations of melatonin inhibit nitric oxide synthase in rat cerebellum. Life Sci 55(24):PL455–PL460
91. Pozo DA, Delgado M, Fernandez-Santos JM, Calvo JR, Gomariz RP, Martin-Lacave I et al (1997) Expression of the Mel1a-melatonin receptor mRNA in T and B subsets of lymphocytes from rat thymus and spleen. FASEB J 11(6):466–473
92. Prise KM, O’Sullivan JM (2009) Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer 9(5):351–360
93. Raghavendra V, Singh V, Kulkarni SK, Agrewala JN (2001) Melatonin enhances Th2 cell mediated immune responses: lack of sensitivity to reversal by naltrexone or benzodiazepine receptor antagonists. Mol Cell Biochem 221(1–2):57–62
94. Rayet B, Gelinas C (1999) Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18(49):6938–6947
95. Reiter RJ, Meltz ML (1995) Melatonin protects human blood lymphocytes from radiation-induced chromosome damage. Mutat Res Lett 346(1):23–31
96. Reiter RJ, Tan D-X, Qi W-B (1998) Suppression of oxygen toxicity by melatonin. Acta Pharmacol Sin 19(6):575–581
97. Reiter RJ, Tan D-X, Burkhardt S (2002) Reactive oxygen and nitrogen species and cellular and organismal decline: amelioration with melatonin. Mech Ageing Dev 123(8):1007–1019
98. Reiter RJ, Rosales-Corral SA, Manchester LC, Tan D-X (2013a) Peripheral reproductive organ health and melatonin: ready for prime time. Int J Mol Sci 14(4):7231–7272
99. Reiter RJ, Tan D-X, Galano A (2013b) Melatonin reduces lipid peroxidation and membrane viscosity. Front Physiol 5:377
100. Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre‐Jimenez M, Qin L (2016) Melatonin as an antioxidant: under promises but over delivers. J Pineal Res 61(3):253–278
101. Rezaeyan A, Fardid R, Haddadi GH, Takhshid MA, Hosseinzadeh M, Najafi M, Salajegheh A (2016a) Evaluating radioprotective effect of hesperidin on acute radiation damage in the lung tissue of rats. J Biomed Phys Eng 6(3):165–174
102. Rezaeyan A, Haddadi GH, Hosseinzadeh M, Moradi M, Najafi M (2016b) Radioprotective effects of hesperidin on oxidative damages and histopathological changes induced by X-irradiation in rats heart tissue. J Med Phys 41(3):182–191
103. Rock KL, Lai JJ, Kono H (2011) Innate and adaptive immune responses to cell death. Immunol Rev 243(1):191–205
104. Rodel F, Frey B, Gaipl U, Keilholz L, Fournier C, Manda K et al (2012) Modulation of inflammatory immune reactions by low-dose ionizing radiation: molecular mechanisms and clinical application. Curr Med Chem 19(12):1741–1750
105. Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V et al (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36(1):1–9
106. Sainz RM, Reiter RJ, Tan DX, Roldan F, Natarajan M, Quiros I et al (2008) Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation‐induced apoptosis in prostate cancer cells in vitro. J Pineal Res 45(3):258–270
107. Sánchez‐Hidalgo M, Lee M, de la Lastra CA, Guerrero JM, Packham G (2012) Melatonin inhibits cell proliferation and induces caspase activation and apoptosis in human malignant lymphoid cell lines. J Pineal Res 53(4):366–373
108. Sangiuliano B, Pérez NM, Moreira DF, Belizário JE (2014) Cell death-associated molecular-pattern molecules: inflammatory signaling and control. Mediat Inflamm 2014:821043
109. Schmuth M, Wimmer MA, Hofer S, Sztankay A, Weinlich G, Linder D et al (2002) Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double‐blind study. Br J Dermatol 146(6):983–991
110. Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJ et al (2011) Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integr Cancer Ther. 1534735411425484
111. Şener G, Atasoy BM, Ersoy Y, Arbak S, Şengöz M, Yeğen BÇ (2004) Melatonin protects against ionizing radiation‐induced oxidative damage in corpus cavernosum and urinary bladder in rats. J Pineal Res 37(4):241–246
112. Serin M, Gülbaş H, Gürses İ, Erkal HŞ, Yücel N (2007) The histopathological evaluation of the effectiveness of melatonin as a protectant against acute lung injury induced by radiation therapy in a rat model. Int J Radiat Biol 83(3):187–193
113. Shi D, Xiao X, Wang J, Liu L, Chen W, Fu L et al (2012) Melatonin suppresses proinflammatory mediators in lipopolysaccharide‐stimulated CRL1999 cells via targeting MAPK, NF‐κB, c/EBPβ, and p300 signaling. J Pineal Res 53(2):154–165
114. Shirazi A, Ghobadi G, Ghazi-Khansari M (2007) A radiobiological review on melatonin: a novel radioprotector. J Radiat Res 48(4):263–272
115. Shirazi A, Mihandoost E, Mohseni M, Ghazi-Khansari M, Rabie Mahdavi S (2013) Radio-protective effects of melatonin against irradiation-induced oxidative damage in rat peripheral blood. Physica Medica 29(1):65–74
116. Somosy Z (2000) Radiation response of cell organelles. Micron 31(2):165–181
117. Szumiel I (2015) Ionizing radiation-induced oxidative stress, epigenetic changes and genomic instability: the pivotal role of mitochondria. Int J Radiat Biol 91(1):1–12
118. Tahamtan R, Monfared AS, Tahamtani Y, Tavassoli A, Akmali M, Mosleh-Shirazi MA et al (2015) Radioprotective effect of melatonin on radiation-induced lung injury and lipid peroxidation in rats. Cell J 17(1):111–120
119. Tain Y-L, Chen C-C, Lee C-T, Kao Y-H, Sheen J-M, Yu H-R et al (2013) Melatonin regulates L-arginine transport and NADPH oxidase in young rats with bile duct ligation: role of protein kinase C. Pediatr Res 73(4–1):395–401
120. Tan D-X, Manchester LC, Reiter RJ, Qi W-B, Karbownik M, Calvo JR (2000) Significance of melatonin in antioxidative defense system: reactions and products. Neurosignals 9(3–4):137–159
121. Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ (2007) One molecule, many derivatives: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res 42(1):28–42
122. Venegas C, García JA, Escames G, Ortiz F, López A, Doerrier C et al (2012) Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J Pineal Res 52(2):217–227
123. Wu ZH, Miyamoto S (2007) Many faces of NF-kappaB signaling induced by genotoxic stress. J Mol Med (Berlin, Germany) 85(11):1187–1202
124. Wu CC, Lu KC, Lin GJ, Hsieh HY, Chu P, Lin SH et al (2012) Melatonin enhances endogenous heme oxygenase‐1 and represses immune responses to ameliorate experimental murine membranous nephropathy. J Pineal Res 52(4):460–469
125. Wu KK, Cheng H-H, Chang T-C (2014) 5-methoxyindole metabolites of L-tryptophan: control of COX-2 expression, inflammation and tumorigenesis. J Biomed Sci 21(1):17
126. Yu Q, Miller SC, Osmond DG (2000) Melatonin inhibits apoptosis during early B‐cell development in mouse bone marrow. J Pineal Res 29(2):86–93
127. Zhang HM, Zhang Y, Zhang BX (2011) The role of mitochondrial complex III in melatonin‐induced ROS production in cultured mesangial cells. J Pineal Res 50(1):78–82
128. Zhao W, Robbins ME (2009) Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: therapeutic implications. Curr Med Chem 16(2):130–143
129. Zhou D, Yu T, Chen G, Brown SA, Yu Z, Mattson M et al (2001) Effects of NF-κB1 (p50) targeted gene disruption on ionizing radiation-induced NF-κB activation and TNFα, IL-1α, IL-1β and IL-6 mRNA expression in vivo. Int J Radiat Biol 77(7):763–772
130. Zhou R, Wang R, Song J, Zhang H, Luo J, Liu H (2015) Melatonin inhibit the angiogenesis of gastric cancer by nuclear receptor. FASEB J 29(1 Supplement):639.5