The efficacy of melatonin against radiotoxicity of iodine-131 and its response to treatment in hyperthyroid patients: a randomized controlled trial
Abstract
Background: Since melatonin is a non-toxic compound with proven radioprotective effects, we aimed to investigate its efficacy in an in-vivo setting in hyperthyroid patients who are treated with iodine-131. This double-blind placebo-controlled study was conducted on hyperthyroid patients referred to nuclear medicine centers in Babol, Iran. We excluded patients suffering from hypertension treated with warfarin, autoimmune diseases, genetic diseases, cancers, smokers, chemical wounded, radiology and radiotherapy workers, and those who were treated with chemotherapy agents. Patients were randomly assigned to receive a capsule containing 300 mg of melatonin powder or a placebo. Just before receiving iodine-131, blood samples were taken from individuals. All 52 female patients received 10 to 20 mCi iodine-131 for treating hyperthyroidism. A second blood sample was taken one hour after the administration of iodine-131. Material and methods: To determine the chromosomal damages before and after receiving radioiodine, we performed the cytokinesis- block micronucleus assay. Also, at phase 2, 6 months follow-up was performed, in which patients’ positive responses to treatment were compared. Results: The findings of this study indicate that the difference in micronucleus formation between the placebo and melatonin groups is not significant. However, a significant difference in the 6 months follow-up revealed that 61.5% and 85.7% of patients had a positive response to treatment in the placebo and melatonin groups, respectively. Conclusions: As one of the first studies dealing with the human in-vivo assessment on the radioprotective effects of melatonin, it was concluded that melatonin has a non-significant positive impact on reducing the rate of chromosomal damages in hyperthyroid patients treated with iodine-131. Nevertheless, the outcome of treatment was significantly higher by melatonin compared to the placebo group.
Keywords: hyperthyroidismmelatoninradiation
References
- Streetman DD, Khanderia U. Diagnosis and treatment of Graves disease. Ann Pharmacother. 2003; 37(7-8): 1100–1109.
- Metso S, Auvinen A, Huhtala H, et al. Increased cancer incidence after radioiodine treatment for hyperthyroidism. Cancer. 2007; 109(10): 1972–1979.
- Ballardin M, Barsacchi R, Bodei L, et al. Oxidative and genotoxic damage after radio-iodine therapy of Graves' hyperthyroidism. Int J Radiat Biol. 2004; 80(3): 209–216.
- Mansour HH, Hafez HF, Fahmy NM, et al. Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Biochem Pharmacol. 2008; 75(3): 773–780.
- Sharma S, Haldar C. Melatonin prevents X-ray irradiation induced oxidative damagein peripheral blood and spleen of the seasonally breeding rodent, Funambulus pennanti during reproductively active phase. Int J Radiat Biol. 2006; 82(6): 411–419.
- Karbownik M, Reiter RJ. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Proc Soc Exp Biol Med. 2000; 225(1): 9–22.
- Reiter RJ, Tan DX, Herman TS, et al. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys. 2004; 59(3): 639–653.
- Brenner B, Wasserman L, Beery E, et al. Variable cytotoxicity of amifostine in malignant and non-malignant cell lines. Oncol Rep. 2003; 10(5): 1609–1613.
- Reiter RJ, Meltz ML, Herman TS. Melatonin: possible mechanisms involved in its 'radioprotective' effect. Mutat Res. 1998; 404(1-2): 187–189.
- Guerrero JM, Reiter RJ. A brief survey of pineal gland-immune system interrelationships. Endocr Res. 1992; 18(2): 91–113.
- Carrillo-Vico A, Lardone PJ, Alvarez-Sánchez N, et al. Melatonin: buffering the immune system. Int J Mol Sci. 2013; 14(4): 8638–8683.
- Reiter RJ, Tan DX, Osuna C, et al. Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci. 2000; 7(6): 444–458.
- Rodriguez C, Mayo JC, Sainz RM, et al. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res. 2004; 36(1): 1–9.
- Galano A, Tan DX, Reiter RJ. On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK. J Pineal Res. 2013; 54(3): 245–257.
- Reiter RJ, Tan DX, Cabrera J, et al. The oxidant/antioxidant network: role of melatonin. Biol Signals Recept. 1999; 8(1-2): 56–63.
- Fenech M, Morley AA. Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivo ageing and low dose X-irradiation. Mutat Res. 1986; 161(2): 193–198.
- Gutiérrez S, Carbonell E, Galofré P, et al. Micronuclei induction by 131I exposure: study in hyperthyroidism patients. Mutat Res. 1997; 373(1): 39–45.
- Baugnet-Mahieu L, Lemaire M, Léonard ED, et al. Chromosome aberrations after treatment with radioactive iodine for thyroid cancer. Radiat Res. 1994; 140(3): 429–431.
- Kacher R, Legal J, Schlumberger M, et al. Biological dosimetry in patients treated with iodine-131 for differentiated thyroid carcinoma. J Nucl Med. 1996; 37(11): 1860–1864.
- Watanabe N, Yokoyama K, Kinuya S, et al. Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus assay. J Nucl Med. 1998; 39(3): 436–440.
- Assayed ME, Abd El-Aty AM. Protection of rat chromosomes by melatonin against gamma radiation-induced damage. Mutat Res. 2009; 677(1-2): 14–20.
- Tahamtan R, Haddadi G, Tavassoli A. The evaluation of melatonin effect against the early effect of ionizing radiation induced lung injury. Journal of Fasa University of Medical Sciences. 2014; 4(1): 120–126.
- Yilmaz S, Yilmaz E. Effects of melatonin and vitamin E on oxidative-antioxidative status in rats exposed to irradiation. Toxicology. 2006; 222(1-2): 1–7.
- Shirazi A, Fardid R, Mihandoost E. Protective effect of low dose melatonin on radiation-induced damage to rat liver. J Biomed Phys Eng. 2012; 2(2): 66–71.
- El-Missiry MA, Fayed TA, El-Sawy MR, et al. Ameliorative effect of melatonin against gamma-irradiation-induced oxidative stress and tissue injury. Ecotoxicol Environ Saf. 2007; 66(2): 278–286.
- Reiter RJ, Meltz ML. Melatonin protects human blood lymphocytes from radiation-induced chromosome damage. Mutat Res. 1995; 346(1): 23–31.
- Vijayalaxmi , Reiter RJ, Sewerynek E, et al. Marked reduction of radiation-induced micronuclei in human blood lymphocytes pretreated with melatonin. Radiat Res. 1995; 143(1): 102–106.
- Vijayalaxmi , Reiter RJ, Herman TS, et al. Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with human volunteers. Mutat Res. 1996; 371(3-4): 221–228.
- Badr FM, El Habit OH, Harraz MM. Radioprotective effect of melatonin assessed by measuring chromosomal damage in mitotic and meiotic cells. Mutat Res. 1999; 444(2): 367–372.
- Bhatia AL, Manda K. Study on pre-treatment of melatonin against radiation-induced oxidative stress in mice. Environ Toxicol Pharmacol. 2004; 18(1): 13–20.
- Monteiro Gil O, Oliveira NG, Rodrigues AS, et al. Cytogenetic alterations and oxidative stress in thyroid cancer patients after iodine-131 therapy. Mutagenesis. 2000; 15(1): 69–75.
- Ballardin M, Gemignani F, Bodei L, et al. Formation of micronuclei and of clastogenic factor(s) in patients receiving therapeutic doses of iodine-131. Mutat Res. 2002; 514(1-2): 77–85.
- Gutiérrez S, Carbonell E, Galofré P, et al. Cytogenetic damage after 131-iodine treatment for hyperthyroidism and thyroid cancer. A study using the micronucleus test. Eur J Nucl Med. 1999; 26(12): 1589–1596.
- Dardano A, Ballardin M, Ferdeghini M, et al. Anticlastogenic effect of Ginkgo biloba extract in Graves' disease patients receiving radioiodine therapy. J Clin Endocrinol Metab. 2007; 92(11): 4286–4289.
- Metso S, Auvinen A, Huhtala H, et al. Increased cancer incidence after radioiodine treatment for hyperthyroidism. Cancer. 2007; 109(10): 1972–1979.
- Iyer NG, Morris LGT, Tuttle RM, et al. Rising incidence of second cancers in patients with low-risk (T1N0) thyroid cancer who receive radioactive iodine therapy. Cancer. 2011; 117(19): 4439–4446.
- Sawka AM, Thabane L, Parlea L, et al. Second primary malignancy risk after radioactive iodine treatment for thyroid cancer: a systematic review and meta-analysis. Thyroid. 2009; 19(5): 451–457.
- Rostami A, Moosavi SA, Dianat Moghadam H, et al. Micronuclei assessment of the radioprotective effects of melatonin and vitamin C in human lymphocytes. Cell J. 2016; 18(1): 46–51.
- Kopjar N, Miocić S, Ramić S, et al. Assessment of the radioprotective effects of amifostine and melatonin on human lymphocytes irradiated with gamma-rays in vitro. Arh Hig Rada Toksikol. 2006; 57(2): 155–163.
- Sewerynek E, Lewiński A. Melatonin inhibits mitotic activity of adrenocortical cells in vivo and in organ culture. J Pineal Res. 1989; 7(1): 1–12.
- Reiter RJ. Oxidative damage to nuclear DNA: amelioration by melatonin. NEL Review. Neuro Endocrinol Lett. 1999; 20(3-4): 145–150.
- Reiter RJ, Tan DX, Gitto E, et al. Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. Pol J Pharmacol. 2004; 56(2): 159–170.
- De Salvia R, Fiore M, Aglitti T, et al. Inhibitory action of melatonin on H2O2- and cyclophosphamide-induced DNA damage. Mutagenesis. 1999; 14(1): 107–112.
