Key result
Romiplostim partially reverses metabolic disruptions from total body irradiation in mice.
Why the study?
Romiplostim was approved to improve survival after acute myelosuppressive radiation exposure, but the mechanism by which it functions as a radiomitigator remains unclear.
Does romiplostim administration correct metabolic disruptions in lethally whole-body-irradiated mice?
Does romiplostim administration correct metabolic disruptions in lethally whole-body-irradiated mice?
Romiplostim partially corrects metabolic disruptions caused by lethal irradiation in mice, suggesting these metabolites could serve as biomarkers for survival likelihood and organ injury recovery.
No clinical implications from this animal study; hypothesis-generating for metabolomic biomarkers of radiation-induced organ injury.
The thrombopoietin receptor agonist romiplostim (RP) was recently approved by the US Food and Drug Administration for improving survival in patients acutely exposed to myelosuppressive doses of radiation. Our previous studies with mice have shown that RP administration after lethal irradiation not only completely rescues irradiated mice but also shows mitigative effects on their hematopoiesis and multiple organ injury, including that of the lung, bone marrow, small intestine, and liver. However, the mechanism by which RP functions as a radiomitigator remains unclear. In the present study, we applied a metabolomics approach, which has the ability to reflect the status of an organism directly and accurately, helping to elucidate the biology of treatment responses. Our results showed that the disruption of several metabolites and pathways in response to total body irradiation was partially corrected by RP administration. Notably, RP-corrected metabolites and pathways have been reported to be indicators of DNA damage and lung, bone marrow, small intestine, and liver injury. Taken together, the present findings suggested that the radiomitigative effect of RP is partially involved in the recovery of organ injury, and the identified metabolites may be a useful biomarker of the survival likelihood following radiation exposure.
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Sato et al. (2022) studied Lethal whole-body irradiation. Romiplostim vs. Total body irradiation alone was evaluated on Serum metabolomic profile. Romiplostim administration partially corrected the disruption of several metabolites and pathways in response to total body irradiation in mice.
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