PURPOSE: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ((225)Ac) nanogenerator, an in vivo generator of alpha- and beta-particle emitting elements. METHODS AND MATERIALS: The animals were injected with 0.35 muCi of the (225)Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. RESULTS: Forty weeks after the (225)Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 +/- 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 +/- 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 +/- 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 +/- 2.5 mg/dL; p <0.001 vs. placebo controls). CONCLUSIONS: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade can offer renal protection in a mouse model of internal alpha-particle irradiation.
RCT Entities:
PURPOSE: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ((225)Ac) nanogenerator, an in vivo generator of alpha- and beta-particle emitting elements. METHODS AND MATERIALS: The animals were injected with 0.35 muCi of the (225)Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. RESULTS: Forty weeks after the (225)Ac injection, the placebo-control mice showed a significant increase in blood ureanitrogen (BUN) (87.6 +/- 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 +/- 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 +/- 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 +/- 2.5 mg/dL; p <0.001 vs. placebo controls). CONCLUSIONS: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade can offer renal protection in a mouse model of internal alpha-particle irradiation.
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