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.