Radiation-Resistant Bacteria Deinococcus radiodurans-Derived Extracellular Vesicles as Potential Radioprotectors

The increasing use of radiation presents a risk of radiation exposure, making the development of radioprotectors necessary. In the previous study, it is investigated that Deinococcus radiodurans (R1-EVs) exert the antioxidative properties. However, the radioprotective activity of R1-EVs remains unclear. In the present study, the protective effects of R1-EVs against total body irradiation (TBI)-induced acute radiation syndrome (ARS) are investigated. To assess R1-EVs' radioprotective efficacy, ARS is induced in mice with 8 Gy of TBI, and protection against hematopoietic (H)- and gastrointestinal (GI)-ARS is evaluated. The survival rate of irradiated mice group decreases substantially after irradiation. In contrast, pretreatment with R1-EVs increases the survival rates of the mice. The administration of R1-EVs provides effective protection against radiation-induced death of bone marrow cells and splenocytes by scavenging reactive oxygen species (ROS). Additionally, R1-EVs protect both intestinal stem and epithelial cells from radiation-induced apoptosis. R1-EVs stimulate the production of short-chain fatty acids in the gastrointestinal tract, suppress proinflammatory cytokines, and increase regulatory T cells in pretreated mice versus the irradiation-only group. Proteomic analysis shows that the R1-EV proteome is significantly enriched with proteins involved in oxidative stress response. These findings highlight R1-EVs as potent radioprotectors with applications against radiation damage and ROS-mediated diseases.