Rationale for the use of melatonin as a protective agent against cosmic radiation and ischemia-reperfusion damage in long term spaceflight

Melatonin(N-acetyl-5-methoxytryptamine) besides acting as a neurohormone is a potent free radical scavenger and antioxidant,
especially effective against free radicals induced by ionizing radiation. This suggests its use for protecting astronauts
against cosmic radiation-induced genotoxicity and carcinogenesis. Melatonin might furthermore be indicated for protecting
astronauts after long-term spaceflights if they have been submitted to a hibernation-like state, since upon arousal after an
extended trip, they will likely suffer ischemia-reperfusion (I/R) injury. Damage from cold I/R is a serious drawback in organ
transplantation field. Several studies, including our own on the liver, have demonstrated that melatonin protected organs from
cold I/R damage. Inducing a hibernation-like state in astronauts is being evaluated as a strategy for surviving long-term
spaceflight. Curiously, hibernating animals endure cold I/R without serious damage; their survival strategies are being
investigated in the hope they might have an outcome in the transplantation field. In this presentation we first briefly review
issues related to damage induced by ionizing radiation upon biomolecules (especially on DNA) and to the protection that can
be afforded by melatonin. Hence we describe the issues regarding mammalian hibernation and organ transplantation that are likely to be transposed to Space Medicine and speculate that melatonin may be indicated in this field as well.