Molecular mechanisms of melatonin’s protection against high-LET radiation: implications for space travel

Abstract

During a deep space mission, the central nervous system (CNS) and other organs are exposed to galactic cosmic rays and solar particle events. Health risks associated with various organs and systems are important issues in a long-term spaceflight. Potential CNS damage during a space mission could alter cognitive functions which might impact performance and individual’s health. The neuronal injury originating from exposure to 56Fe particle irradiation involves the elevated oxidative stress which can be inhibited by melatonin pretreatment. Melatonin exerts potent neuroprotective effects against carbon ion-induced mitochondrial dysfunction and apoptosis in the mouse brain. A significant increase in the count of immature neurons and proliferating cells was detected in the mice under 56Fe particle irradiation cotreated with the melatonin metabolite, AFMK. Melatonin treatment also significantly reduced the carbon ion-induced apoptotic cells and elevated oxidative stress in the mouse testis. The results suggest that melatonin treatment is a potential strategy to protect against space radiation hazards. Spaceflight-induced molecular, cellular, and physiologic changes lead to alterations across many organs and systems. Epigenetic, gene expression, inflammatory, and metabolic responses to spaceflight should be examined and means to safe-guard against these changes in upcoming missions. Precision medicine will be crucial for assessing and augmenting efficacy of melatonin or other medications in astronauts. In addition, enhancing radio-resistance of humans is a novel strategy for a long-term space mission. Further investigations with a combination of melatonin and other novel technologies are warranted to better alleviate HZE particle irradiation-induced damage to astronauts on long-term space exploration missions.

Melatonin: A Promising Drug to Ameliorate Main Human Space Exploration Risks

“…Melatonin treatment also significantly prevented carbon ion irradiation induced mitochondrial dysfunction and apoptosis in mouse brain, and alleviated the carbon induced increase in the percentage of apoptotic cells and elevated oxidative stress in mouse testis. 34 Melatonin has also shown radioprotective effects in erythrocytes, ovary, thyroid and liver of irradiated rodents, as well as in human lymphocites. 30 In humans, a double-blind placebo-controlled study in patients with rectum cancer undergoing radiotherapy examined the radioprotective effects of melatonin (20 mg/day, 5 days a week, during 28 days) on blood cell counts.…”

Cancer Studies under Space Conditions: Finding Answers Abroad

“…FYN upregulation reduces ROS, diminishing the indirect damage of ionising radiation [ 92 ]. Furthermore, Liu and Reiter [ 93 ] found that exposure of neurons to iron ion particle radiation leads to increased ROS levels that can be counteracted by melatonin treatment. This treatment also increased the number of immature neurons and proliferating cells in mice, which is a sign of an enhanced regenerative capacity of the neurons [ 93 ].…”

“…Ionising radiation produces ROS in cells and the extracellular environment, and several authors have discovered an upregulation of ROS scavengers and an increase in intercellular signalling of inflammation following irradiation. However, these changes can be counteracted by administering redox scavengers or antioxidants, effectively reducing the amount of ROS in the extracellular environment and possibly reducing intercellular inflammatory signalling, hinting at the possibility of using pharmaceutical protection against radiation-induced damage [ 89 , 90 , 91 , 92 , 93 ].…”