Prevention of radiation-induced nephropathy and fibrosis in a model of bone marrow transplant by an angiotensin II receptor blocker. Exp Biol Med (Maywood) 2001 Dec;226(11):1016-23
Date
12/18/2001Pubmed ID
11743137DOI
10.1177/153537020122601108Scopus ID
2-s2.0-0035758111 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
Nephropathy, interstitial pneumopathy, and renal and lung fibrosis are major complications of bone marrow transplantation (BMT). This study evaluated the antifibrotic property of an angiotensin II (A2) type-1 receptor blocker (L-159,809) and compared it with those of Captopril and Enalapril, two angiotensin-converting enzyme (ACE) inhibitors, in a rat model of BMT. Male WAG/Rij/MCW rats received a preparative regimen of 60 mg/kg body wt of cytoxan (i.p., Days 9 and 8) and 18.5 Gy of total body irradiation (TBI) in six twice daily fractions (Days 2, 1, and 0) followed immediately (Day 0) by BMT. Modifiers were given in drinking water from Day 10 until autopsy, 8 weeks after BMT. Rats treated with TBI plus cytoxan alone developed severe nephropathy. Trichrome staining showed marked collagen deposition in glomeruli, renal interstitium, and renal arteries and arterioles (especially in their adventitia). Collagen deposition and renal damage were markedly reduced by the three modifiers. Of the three, L-158,809-treated rats had slightly thinner vessels and slightly less collagen than nonirradiated normal controls. The study shows the effectiveness of these drugs in the protection of the renal parenchyma from the development of radiation-induced fibrosis. It also indicates a role for angiotensin II in the modulation of collagen synthesis.
Author List
Molteni A, Moulder JE, Cohen EP, Fish BL, Taylor JM, Veno PA, Wolfe LF, Ward WFMESH terms used to index this publication - Major topics in bold
AldosteroneAngiotensin Receptor Antagonists
Animals
Antihypertensive Agents
Bone Marrow Transplantation
Captopril
Disease Models, Animal
Enalapril
Enzyme Inhibitors
Fibrosis
Imidazoles
Kidney Diseases
Male
Radiotherapy
Rats
Tetrazoles
Time Factors