Angiotensin converting enzyme inhibitor captopril does not prevent acute gastrointestinal radiation damage in the rat.
Retrospective examination of acute gastrointestinal (GI) lethality in our rat bone marrow transplantation studies showed indication of a protective effect, with a dose modifying factor (DMF) of 1.06 (95% confidence interval: 0.99-1.12). A randomized study, using the same experimental design, was conducted specifically to look for GI protection. Animals were randomized into captopril or non-drug arms and irradiated in a 6-fraction total body irradiation regimen, followed by bone marrow transplantation. Rats received captopril in the drinking water at 500 mg/l (70 mg/kg/day), starting 9 days prior to irradiation and continuing throughout the experiment. The 50% lethal dose at 6 days was 20.8 (20.4-21.7) Gy in the non-drug arm and 20.6 (20.3-20.9) Gy in the captopril arm, for a DMF of 0.99 (0.94-1.04). If the randomized and historical studies are combined the DMF is 1.00 (0.93-1.05). We are unable to find any evidence that the angiotensin converting enzyme (ACE) inhibitor captopril provides protection from acute GI injury in this model. Clearly, it should not be assumed that captopril will modulate radiation reactions in all tissues.
Moulder
J E
JE
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA. jmoulder@its.mcw.edu
Fish
B L
BL
D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D016026:Bone Marrow Transplantation; D002216:Captopril / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000532:radiotherapy; D007928:Lethal Dose 50; D008297:Male; D011446:Prospective Studies; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D012189:Retrospective Studies; D014916:Whole-Body Irradiation
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril