Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells

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Abstract
Accidental radiation exposure that is due to a nuclear accident or terrorism using radioactive materials has severe detrimental effects on human health, and it can manifest as acute radiation syndrome depending on the dose and distribution of the radiation. Therefore, the development of radiation countermeasure agents is urgently needed to protect humans against radiation injury. Besides nuclear DNA, the mitochondria are important targets of ionizing radiation (IR) because these organelles generate reactive oxygen species (ROS). Recently, we revealed that mitochondrial ROS‐activated cell signaling is associated with IR‐induced tumor formation. Here, we investigated the effectiveness of ascorbic acid and epicatechin (EC) in scavenging ROS as radiation countermeasure agents by using human cells and mouse. Preradiation and postradiation treatments with EC mitigate ROS‐mediated mitochondrial damage, IR‐induced oxidative stress responses including reduction of superoxide dismutase activity, and elevated nuclear factor erythroid 2–related factor 2 expression, and they improve human fibroblast survival. As well as in vitro , EC mitigated ROS‐mediated mitochondrial damage after exposure to IR in vivo in mouse platelets. Furthermore, oral administration of EC significantly enhanced the recovery of mouse hematopoietic cells from radiation injury in vivo . In summary, EC is a potentially viable countermeasure agent that is immediately effective against accidental IR exposure by targeting mitochondria‐mediated oxidative stress.—Shimura, T., Koyama, M., Aono, D., Kunugita, N. Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells. FASEB J. 33, 6867–6876 (2019). www.fasebj.org
Funding Information
  • Ministry of Health, Labour and Welfare
  • National Institute for Fusion Science (NIFS13KOBA028)

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