Irradiation Causes Alterations of Polyamine, Purine, and Sulfur Metabolism in Red Blood Cells and Multiple Organs

Investigating the metabolic effects of radiation is critical to understand the impact of radiotherapy, space travel, and exposure to environmental radiation. In patients undergoing hemopoietic stem cell transplantation, iron overload is a common risk factor for poor outcomes. However, no studies have interrogated the multiorgan effects of these treatments concurrently. Herein, we use a model that recapitulates transfusional iron overload, a condition often observed in chronically transfused patients. We applied an omics approach to investigate the impact of both the iron load and irradiation on the host metabolome. The results revealed dose-dependent effects of irradiation in the red blood cells, plasma, spleen, and liver energy and redox metabolism. Increases in polyamines and purine salvage metabolites were observed in organs with high oxygen consumption including the heart, kidneys, and brain. Irradiation also impacted the metabolism of the duodenum, colon, and stool, suggesting a potential effect on the microbiome. Iron infusion affected the response to radiation in the organs and blood, especially in erythrocyte polyamines and spleen antioxidant metabolism, and affected glucose, methionine, and glutathione systems and tryptophan metabolism in the liver, stool, and the brain. Together, the results suggest that radiation impacts metabolism on a multiorgan level with a significant interaction of the host iron status.

探究辐射的代谢效应，对于理解放射治疗、太空旅行以及环境辐射暴露所产生的影响至关重要。在接受造血干细胞移植的患者中，铁过载是导致不良预后的常见风险因素。然而，目前尚无研究同时探究这两类干预措施的多器官效应。本研究采用可模拟输血相关性铁过载的动物模型——该病症常见于长期接受输血治疗的患者。我们运用组学（omics）手段，探究铁负荷与辐射照射二者对宿主代谢组（metabolome）的影响。研究结果显示，辐射照射对红细胞、血浆、脾脏及肝脏的能量代谢与氧化还原代谢均呈现剂量依赖性影响。在心脏、肾脏与大脑等高氧耗器官中，观测到多胺与嘌呤补救代谢产物的水平升高。辐射照射还会影响十二指肠、结肠与粪便的代谢特征，提示其可能对肠道微生物组产生作用。铁输注会改变机体器官与血液对辐射照射的应答反应，尤其会影响红细胞多胺代谢与脾脏抗氧化代谢；同时还会改变肝脏、粪便及大脑中的葡萄糖、甲硫氨酸、谷胱甘肽系统以及色氨酸代谢通路。综合来看，上述结果表明，辐射照射可在多器官层面影响机体代谢，且宿主的铁负荷状态会与辐射产生显著的交互作用。