TY - JOUR
T1 - Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs
AU - Fish, Brian L.
AU - Gao, Feng
AU - Narayanan, Jayashree
AU - Bergom, Carmen
AU - Jacobs, Elizabeth R.
AU - Cohen, Eric P.
AU - Moulder, John E.
AU - Orschell, Christie M.
AU - Medhora, Meetha
N1 - Publisher Copyright:
© 2016 Health Physics Society.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at 24 mg m-2 d-1 started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg-1 d-1 from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.
AB - The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain, and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study, the authors have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at 24 mg m-2 d-1 started orally in the drinking water at 7 d after irradiation and continued to ≥150 d) mitigated late effects in the lungs and kidneys after 12.5-Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 d after 13-Gy leg-out PBI. Furthermore, lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg-1 d-1 from days 1-14), which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, acute and delayed radiation injuries in multiple organs were mitigated.
KW - kidneys
KW - lungs, rodent
KW - radiation damage
KW - x rays
UR - http://www.scopus.com/inward/record.url?scp=84991056212&partnerID=8YFLogxK
U2 - 10.1097/HP.0000000000000554
DO - 10.1097/HP.0000000000000554
M3 - Article
C2 - 27682899
AN - SCOPUS:84991056212
SN - 0017-9078
VL - 111
SP - 410
EP - 419
JO - Health Physics
JF - Health Physics
IS - 5
ER -