Our previous research demonstrated that one
subcutaneous injection of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) 24 hours (h) before irradiation (8.75 Gy) increased mouse survival by 75%. However, the protective mechanism of
17-DMAG is currently unknown. The present study aimed to investigate whether
oral administration of
17-DMAG was also radioprotective and the potential role it may play in radioprotection.
RESULTS: A single dose of orally pre-administered (24, 48, or 72 h)
17-DMAG (10 mg/kg) increased irradiated mouse survival, reduced
body weight loss, improved water consumption, and decreased facial
dropsy, whereas orally post-administered
17-DMAG failed. Additional oral doses of pre-treatment did not improve 30-day survival. The protective effect of multiple pre-administrations (2-3 times) of
17-DMAG at 10 mg/kg was equal to the outcome of a single pre-treatment. In 17-DMAG-pretreated mice, attenuation of bone marrow aplasia in femurs 30 days after irradiation with recovered expressions of cluster of differentiation 34, 44 (CD34, CD44), and
survivin in bone marrow cells were observed.
17-DMAG also elevated serum
granulocyte-colony stimulating factor (
G-CSF), decreased serum fms-related
tyrosine kinase 3
ligand, and reduced white blood cell depletion.
17-DMAG ameliorated small intestinal histological damage, promoted recovery of villus heights and intestinal crypts including stem cells, where increased
leucine-rich repeat-containing
G-protein coupled receptor 5 (Lgr5) was found 30 days after irradiation.
CONCLUSIONS: