Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys Journal Article

  


Authors: Jaggi, J. S.; Seshan, S. V.; McDevitt, M. R.; Sgouros, G.; Hyjek, E.; Scheinberg, D. A.
Article Title: Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys
Abstract: 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 (225Ac) nanogenerator, an in vivo generator of α- and β-particle emitting elements. Methods and Materials: The animals were injected with 0.35 μCi of the 225Ac 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 225Ac 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 α-particle irradiation. © 2006 Elsevier Inc.
Keywords: immunohistochemistry; controlled study; histopathology; microscopy; placebo; nonhuman; animals; mice; animal tissue; kidney disease; radiotherapy; animal experiment; animal model; urea nitrogen blood level; in vivo study; mice, inbred balb c; radiation dosage; kidney; drug mechanism; dosimetry; angiotensin ii; irradiation; transforming growth factor beta1; radiation-protective agents; drug absorption; spironolactone; patient treatment; captopril; biological organs; imidazoles; plasminogen activator inhibitor 1; neurology; electron; random allocation; radiation injuries, experimental; alpha radiation; alpha particles; actinium; actinium 225; kidney tubules; blood chemistry; 2 ethyl 5,7 dimethyl 3 [4 [2 (2h tetrazol 5 yl)phenyl]benzyl]imidazo[4,5 b]pyridine; angiotensin-converting enzyme inhibitors; renal protection; accidents; aldosterone escape; internal radiation; radiation nephropathy; aldosterone antagonists; blood urea nitrogen; tetrazoles
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 64
Issue: 5
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2006-04-01
Start Page: 1503
End Page: 1512
Language: English
DOI: 10.1016/j.ijrobp.2005.11.036
PUBMED: 16503385
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-33645371999&partnerID=40&md5=324aeca4fcec07a54a93339f475da4db
Notes: --- - "Cited By (since 1996): 29" - "Export Date: 4 June 2012" - "CODEN: IOBPD" - "Source: Scopus"
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MSK Authors
  1. Jaspreet Jaggi
    21 Jaggi
  2. Michael R Mcdevitt
    144 Mcdevitt
  3. David Scheinberg
    499 Scheinberg
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