Mitigation of Radiation-Induced Pneumonitis and Pulmonary Vascular Injury Using Combined Therapy: Angiotensin Converting Enzyme Inhibitors and Superoxide Dismutase (SOD) Mimetics
Radiation Research Society
Annual Meeting of the Radiation Research Society
Aim: To investigate potential therapies for radiation-induced lung injury. In this study we examine the effectiveness of independent and combined treatment using angiotensin converting enzyme (ACE) inhibitors and a super oxide dismutase (SOD) mimetic as mitigators of radiation injury after total body irradiation (TBI). Methods: Rats (WAG/RijCmcr) were irradiated with a single dose (11Gy, TBI) followed by a syngenic bone marrow transplant. P O S T E R S E S S I O N S 60 Poster Sessions Rats were then treated with captopril (100 mg/m2/day) or enalapril (10 mg/m2/day) in their drinking water or with the super oxide dismutase (SOD) catalase mimetic EUK-207 (1.8 mg/m2/day) alone or in combination starting at approximately one wk after TBI, continuing until the endpoint. Rats were studied 6 wks after TBI and indices of health as well as heart and lung structure and function were measured. Results: Body weight was significantly decreased by TBI and not improved by any treatment schedule. Hematocrit tended to be decreased, but not significantly, in TBI rats and mostly unchanged by treatment. Right ventricular hypertrophy (RVH) was significantly increased by TBI. RVH was mitigated by captopril and EUK alone or in combination, but not by enalapril + EUK. Total lung ACE activity was significantly decreased by TBI, this effect was significantly mitigated by treatment with EUK alone or in combination with either ACE inhibitor. Pulmonary vascular resistance (PVR) was significantly increased by TBI. PVR was significantly decreased by treatment with captopril and EUK alone or in combination, but not by enalapril + EUK. Conclusions: Radiation induced injury appears to be mitigated by treatment with EUK and/or captopril, but not enalapril + EUK. This work was funded by RC1 AI 81294 and NIH/NIAID agreements U19-AI- 67734. Dosimetry was done by the CMCR Irradiation Core at MCW; histology was done in the Children’s Research Institute at MCW under direction of Dr. Paula North.