The melatonin immunomodulatory actions in radiotherapy

Abstract

Radiotherapy has a key role in cancer treatment in more than half of patients with cancer. The management of severe side effects of this treatment modality is a limiting factor to appropriate treatment. Immune system responses play a pivotal role in many of the early and late side effects of radiation. Moreover, immune cells have a significant role in tumor response to radiotherapy, such as angiogenesis and tumor growth. Melatonin as a potent antioxidant has shown appropriate immune regulatory properties that may ameliorate toxicity induced by radiation in various organs. These effects are mediated through various modulatory effects of melatonin in different levels of tissue reaction to ionizing radiation. The effects on the DNA repair system, antioxidant enzymes, immune cells, cytokines secretion, transcription factors, and protein kinases are most important. Moreover, anti-cancer properties of melatonin may increase the therapeutic ratio of radiotherapy. Clinical applications of this agent for the management of malignancies such as breast cancer have shown promising results. It seems anti-proliferative, anti-angiogenesis, and stimulation or suppression of some immune cell responses are the main anti-tumor effects of melatonin that may help to improve response of the tumor to radiotherapy. In this review, the effects of melatonin on the modulation of immune responses in both normal and tumor tissues will be discussed.

Oxidative Stress in Radiation-Induced Cardiotoxicity

“…Vitamin E Amygdala, peanut, and sunflower seeds [70] Reduce the activity of NADPH oxidase and inhibit lipid peroxidation and downregulate NF-κB [19] Antioxidation, anti-inflammation, and a decline of the risk of coronary heart diseases [75,76] Silymarin Milk thistle [77] Stimulate the expression of Nrf2 and downregulate NF-κB [14] Suppression of oxidative stress and inflammation and antiatherosclerosis [14,80] Resveratrol Grapes and red wine [81,82] Reduce the uncoupling of NADPH oxidase and eNOS and upregulate antioxidant defense enzymes [81,82] Antioxidative and anti-inflammatory properties against cardiovascular diseases [81,82,85] Lycopene Tomatoes, watermelons, pink grapefruit, apricots, pink guava, and papaya [29] Scavenge singlet oxygen, nitrogen dioxide, sulfur, and sulfonyl-free radicals [25] Prevention of the oxidation of DNA, lipid, and proteins [25,86] Melatonin Cereals, olives, walnuts, tomatoes, pineapples, ginger, and beans [63] Donate two electrons directly and stimulate the enzymatic antioxidant system indirectly [26,91] Suppression of oxidative stress and prevention of RIHD [90,91] Hesperidin Oranges, lemons, grapes, and olive oil [30] Passivate NADPH oxidase and inhibit TGF-β1 mRNA expression [95] Inhibition of oxidative stress, cardiac hypertrophy, and cardiac remodeling [95,96] 9 Oxidative Medicine and Cellular Longevity process of lipid peroxidation. Therefore, Vit E can reduce the risk of coronary heart disease [14].…”

“…Radiation can not only change the upstream source of ROS but also change the balance of endogenous antioxidant defense mechanisms, including glutathione, ascorbic acid, catalase, and superoxide dismutase (SOD) [25]. The inhibition of antioxidant enzymes is one of the important effects of ionizing radiation on irradiated organs and off-site organs, which leads to the production and accumulation of ROS [26]. ROS can react randomly with cellular lipids, proteins, and nucleic acids, and cause oxidative stress, thus damaging these macromolecules [25].…”

The emergence of melatonin in oncology: Focus on colorectal cancer

“…Having in mind this status quo, which characterizes melatonin as a natural alternative for the prevention and treatment of intestinal inflammatory traits, undoubtedly this indoleamine may have applications for the colon. Accordingly, being the colon one of most affected tissues by chronic immunoinflammatory responses after ionizing radiotherapy, melatonin is a promising natural agent for the amelioration of acute and late consequences of radiotherapy . Consequently, it seems reasonable to clarify the mechanism by which melatonin affects the inflammatory phenotype and the treatment conditions in which its effects are beneficial for patients with inflammatory bowel disorders, including CRC.…”

Pharmacoprophylactic and Pharmacotherapeutic Approaches to Mitigating the Damaging Effects of Ionizing Radiation: Review of Information Sources

“…Мелатонін (рисунок 19) є нейромедіатором (у гіпокампі), гормоном (блокує синтез і секрецію гіпофізом гонадотропінів), імуномодулятором (активізує імунну систему, знижує секрецію мелатоніну, викликає інволюцію тимусу), антиканцерогеном (гальмує проліферацію клітин), антиоксидантом, має рецептори на всіх клітинах (мембранні та ядерні), що в цілому гальмує старіння і підвищує адаптацію організму. Як антиоксидант мелатонін є ендогенним, виділяється переважно вночі, амфіфільний (водо-та жиророзчинний), активніший за токоферол та глутатіон [35,2,80,39].…”

“…перед опроміненням), який застосовується переважно при отруєннях «тіоловими отрутами»[72,3,41].Рисунок 13 -Цистаміну гідрохлорид (дигідрохлорид біс-(β-аміноетил)-дисульфіду)Найгетерогеннішою групою радіопротекторів з негіпоксичним механізмом дії виступають антиоксиданти(ФЗД=1,1-1,3). До РПантиоксидантів належать[80,39]:-ендогенні ферменти: СОД, каталаза, глутатіон-пероксидаза, трансферин, церулоплазмін, меланін та інші; -синтетичні антиоксиданти: дибунол (іонол) (рисунок 14), мексидол (етилметилгідроксипіридину сукцинат) (рисунок 15) та інші; -нітроксидвивільнюючі сполуки: темпол (рисунок 16), ізосорбіду мононітрат (рисунок 17), JP4-039 та інші; -поліфенольні сполуки рослинного походження: кверцетин (рисунок 18) та інші;…”