Abstract
Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation risks to astronauts is critical. We investigated radiation-induced endothelial cell damage and its mitigation by LGM2605, a radioprotector with antioxidant and free radical scavenging properties. We used an in vitro model of lung vascular networks (flow-adapted endothelial cells; FAECs), exposed to gamma rays, low/higher linear energy transfer (LET) protons (3–4 or 8–10 keV/µm, respectively), and mixed field radiation sources (gamma and protons), given at mission-relevant doses (0.25 gray (Gy)–1 Gy). We evaluated endothelial inflammatory phenotype, NLRP3 inflammasome activation, and oxidative cell injury. LGM2605 (100 µM) was added 30 min post radiation exposure and gene expression changes evaluated 24 h later. Radiation induced a robust increase in mRNA levels of antioxidant enzymes post 0.25 Gy and 0.5 Gy gamma radiation, which was significantly decreased by LGM2605. Intercellular cell adhesion molecule-1 (ICAM-1) and NOD-like receptor protein 3 (NLRP3) induction by individual or mixed-field exposures were also significantly blunted by LGM2605. We conclude that LGM2605 is a likely candidate to reduce tissue damage from space-relevant radiation exposure.
Highlights
Updated measurements of charged particle fluxes during the transit from Earth to Mars conducted with the Radiation Assessment Detector inside the Mars Science Laboratory spacecraft [1], as well as on site measurements by Curiosity of Martian surface radiation fluxes [2,3], provided valuable knowledge for a better evaluation of potential health hazards associated with human space missions [4,5]
In further studies using space-relevant radiation, we have shown that LGM2605 acts as a mitigator of radiation-induced increases in inflammatory signals in human lung sections [22]
In order to determine whether LGM2605, given post radiation exposure, is an effective mitigator of space radiation-induced vascular damage, we evaluated the dampening of the endothelial inflammatory phenotype and its functional effects, and NOD-like receptor protein 3 (NLRP3) inflammasome activation
Summary
Updated measurements of charged particle fluxes during the transit from Earth to Mars conducted with the Radiation Assessment Detector inside the Mars Science Laboratory spacecraft [1], as well as on site measurements by Curiosity of Martian surface radiation fluxes [2,3], provided valuable knowledge for a better evaluation of potential health hazards associated with human space missions [4,5]. While space travel opens the door to numerous exciting and fascinating possibilities, it is associated with such risks that impact the crewmember’s health and performance, jeopardizing the success of future missions to distant destinations. Designing mitigation of risks to astronauts, such as those from exposure to space radiation during transit and after landing/colonization, is an unmet need. GCRs tend to be highly energetic; highly penetrating particles that are not stopped by the modest depths of shielding on a typical spacecraft
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