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- W4236445721 abstract "Exposure to ionizing radiation (IR) increases the production of reactive oxygen species (ROS) not only by the radiolysis of water but also through IR-induced perturbation of the cellular metabolism and disturbance of the balance of reduction/oxidation reactions. Our recent studies showed that the increased production of intracellular ROS induced by IR contributes to IR-induced late effects, particularly in the hematopoietic system, because inhibition of ROS production with an antioxidant after IR exposure can mitigate IR-induced long-term bone marrow (BM) injury. Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin also has the ability to regulate cellular metabolism and ROS production by activating AMP-activated protein kinase. Therefore, we examined whether metformin can ameliorate IR-induced long-term BM injury in a total-body irradiation (TBI) mouse model. Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs). These changes were associated with a significant increase in BM HSC frequency, a considerable improvement in in vitro and in vivo HSC function, and complete inhibition of upregulation of p16(Ink4a) in HSCs after TBI. These findings demonstrate that metformin can attenuate TBI-induced long-term BM injury at least in part by inhibiting the induction of chronic oxidative stress in HSCs and HSC senescence. Therefore, metformin has the potential to be used as a novel radioprotectant to ameliorate TBI-induced long-term BM injury." @default.
- W4236445721 created "2022-05-12" @default.
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- W4236445721 date "2015-10-01" @default.
- W4236445721 modified "2023-10-16" @default.
- W4236445721 title "Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice" @default.
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- W4236445721 doi "https://doi.org/10.1016/j.freeradbiomed.2015.05.045" @default.
- W4236445721 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26086617" @default.
- W4236445721 hasPublicationYear "2015" @default.
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