Angiotensin-converting enzyme inhibitors (ACEi) are effective mitigators of radiation nephropathy. To date, their experimental use has been in fixed-dose regimens. In clinical use, doses of ACEi and other medication may be escalated to achieve greater benefit. We therefore used a rodent model to test the ACEi enalapril as a mitigator of radiation injury in an escalating-dose regimen. Single-fraction partial-body irradiation (PBI) with one hind limb out of the radiation field was used to model accidental or belligerent radiation exposures. PBI doses of 12.5, 12.75 and 13 Gy were used to establish multi-organ injury. One third of the rats underwent PBI alone, and two thirds of the rats had enalapril started five days after PBI at a dose of 30 mg/l in the drinking water. When there was established azotemic renal injury enalapril was escalated to a 60 mg/l dose in half of the animals and then later to a 120 mg/l dose. Irradiated rats on enalapril had significant mitigation of combined pulmonary and renal morbidity and had significantly less azotemia. Dose escalation of enalapril did not significantly improve outcomes compared to fixed-dose enalapril. The current data support use of the ACEi enalapril at a fixed and clinically usable dose to mitigate radiation injury after partial-body radiation exposure.
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1 March 2016
Research Article|
March 02 2016
Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury
Eric P. Cohen;
Eric P. Cohen
aNephrology Section, University of Maryland, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland; and
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Brian L. Fish;
Brian L. Fish
bDepartment of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
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John E. Moulder
John E. Moulder
1
bDepartment of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
1Address for correspondence: Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226; email: jmoulder@mcw.edu.
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Radiat Res (2016) 185 (3): 313–318.
Article history
Received:
August 24 2015
Accepted:
January 12 2016
Citation
Eric P. Cohen, Brian L. Fish, John E. Moulder; Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury. Radiat Res 1 March 2016; 185 (3): 313–318. doi: https://doi.org/10.1667/RR4243.S1
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