Radioprotectors: Biological & Clinical Perspectives- Review on the Properties of Melatonin

Background
Ionizing radiation (IR) is regarded as one of the most commonly used methods for diagnostic and treating diseases including cancers; which may lead to various complications despite its many medical uses. Radiation therapy, as one of the most effective modality, plays an important role in treatment and prevention of cancer recurrence or metastasis. Due to different radiosensitivity of healthy tissues around the tumor, variable responses to IR could be obtained; which may terminate in several detrimental effects. Therefore, the acute and late toxicity of radiation therapy in healthy tissues can be expressed as a major limitation for radiation dose delivery to tumors.
Protection against the biological effects of IR could be implemented by both physical and chemical approaches. The basis of physical protection is illustrated as the use of appropriate radiation field and lead protectors or shields, radiation dose proportional to the target, reduction in duration of irradiation, and increase in the distance from the radiation
source. Chemical protection is elucidated as reducing the detrimental effects of IR by natural and synthetic compounds of chemical or plant origin; which can be used orally, injectably or topically. Presence of these compounds at the moment of irradiation and free radical’s production, can reduce or prevent the adverse effects of IR by distinct mechanisms. In addition to protecting patients in medical applications, radioprotectors are utilized to protect workers during occupational exposure and public members via accidental exposure. Peculiarities of an ideal radioprotector could be categorized as; 1) selective differentiation of healthy cells from tumoral 2) protecting healthy tissues, while not protecting tumoral ones, 3) optimal stability, 4) administration suitable method (preferably oral), 5) lack of drug interactions, 6) easily penetration into the cells, 7) minimum degree of toxicity and 8) accessibility and reasonable price. However, despite huge bulk of studies, non-toxic and effective radioprotector for human use has not yet been officially ascertained. One of the known radioprotector agents is melatonin, which is a fat-soluble compound derived from the amino acid tryptophan. Melatonin (N-acetyl-5-methoxytryptamine) by molecular formula C13H16N2O2, is a hormone that is secreted at night in the absence of light by the pineal gland behind the third ventricle of the brain of all mammals, including humans. Accumulating evidence demonstrated that melatonin is a strong antioxidant, indicating its properties both in a direct (scavenging free radicals) and indirect strategies (stimulating the activation of antioxidant enzymes). The investigations exhibited by researchers reported that melatonin could alleviate the deleterious complications caused by IR in different tissues of animals such as lung, colon, eye, spleen and spinal cord. Moreover, enough published papers have manifested the radio sensitivity effect of melatonin on cancer cells through increasing cell apoptosis.
Results & Conclusion
Melatonin with several features including stimulation the activity of antioxidant enzymes (e.g. glutathione) and free radicals scavengering, inhibition of the activity of pro- oxidant enzymes, increasing the expression of anti-apoptotic genes and decreasing the expression of pro-apoptotic genes in healthy tissue, easily penetration, accumulation with the highest concentration in different parts of the cell, low toxicity, no proof of adverse effects, suitable administration method (oral), availability and cheap price could be considered as a promising radioprotector. Noteworthy to mention that the presence of two properties of radioprotection and radiosensitization simultaneously can confirm the role of melatonin as a strong unique compound. More confirming research and clinical trials could clarify the ambiguity and uncertainty of clinical use of this compound.