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2018 ; 8
(1
): 10659
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The thrombopoietin mimetic romiplostim leads to the complete rescue of mice
exposed to lethal ionizing radiation
#MMPMID30006622
Yamaguchi M
; Hirouchi T
; Yokoyama K
; Nishiyama A
; Murakami S
; Kashiwakura I
Sci Rep
2018[Jul]; 8
(1
): 10659
PMID30006622
show ga
For the primary treatment of emergency exposure to high-dose radiation, such as
in the event of a radiation accident, the top priority is the reconstitution and
restoration of haematopoiesis. In most radiation accidents, drug therapy is
chosen as the most suitable treatment; the chosen drug should already be approved
domestically, stably supplied and regularly stockpiled. In the present study, a
single administration of romiplostim (RP), an approved thrombopoietin receptor
agonist, produced a 100% survival rate in C57BL/6?J mice exposed to a lethal dose
(7?Gy) of (137)Cs ?-rays, and all irradiated mice survived for more than 30 days
with both 3- and 5-day consecutive administrations. By day 30, the peripheral
blood cells, bone marrow cells and haematopoietic progenitor cells of the
RP-administered irradiated mice had all recovered to a level that was not
significantly different from that in non-irradiated mice. In contrast to
myelosuppression, which did not fully recover until day 30, the expression of
several bone marrow cell surface antigens recovered sooner, and DNA repair
concurrently increased in haematopoietic cells, speeding the resolution of double
strand breaks and reducing the rates of apoptosis. These findings suggest that RP
may be a clinic-ready countermeasure to treat victims of radiation accidents.
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