Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs

Brian L. Fish, Feng Gao, Jayashree Narayanan, Carmen Bergom, Elizabeth R. Jacobs, Eric P. Cohen, John E. Moulder, Christie Orschell, Meetha Medhora

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalHealth Physics
Volume111
Issue number5
DOIs
StatePublished - Nov 1 2016

Fingerprint

Lisinopril
Radiation Injuries
Leg
Angiotensin-Converting Enzyme Inhibitors
Anti-Bacterial Agents
Acute Radiation Syndrome
National Institute of Allergy and Infectious Diseases (U.S.)
Radiation
Kidney
Lung
Radiation Oncology
Multiple Trauma
Radiation Effects
Granulocyte Colony-Stimulating Factor
Drinking Water
Brain Injuries
Accidents
Intercellular Signaling Peptides and Proteins
Bone Marrow
Morbidity

Keywords

  • kidneys
  • lungs, rodent
  • radiation damage
  • x rays

ASJC Scopus subject areas

  • Epidemiology
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

Cite this

Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs. / Fish, Brian L.; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R.; Cohen, Eric P.; Moulder, John E.; Orschell, Christie; Medhora, Meetha.

In: Health Physics, Vol. 111, No. 5, 01.11.2016, p. 410-419.

Research output: Contribution to journalArticle

Fish, BL, Gao, F, Narayanan, J, Bergom, C, Jacobs, ER, Cohen, EP, Moulder, JE, Orschell, C & Medhora, M 2016, 'Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs', Health Physics, vol. 111, no. 5, pp. 410-419. https://doi.org/10.1097/HP.0000000000000554
Fish, Brian L. ; Gao, Feng ; Narayanan, Jayashree ; Bergom, Carmen ; Jacobs, Elizabeth R. ; Cohen, Eric P. ; Moulder, John E. ; Orschell, Christie ; Medhora, Meetha. / Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs. In: Health Physics. 2016 ; Vol. 111, No. 5. pp. 410-419.
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