Prevention of radiation-induced nephropathy and fibrosis in a model of bone marrow transplant by an angiotensin II receptor blocker.
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.
Molteni
A
A
Department of Pathology, University of Missouri at Kansas City, Kansas City, Missouri 64106, USA. moltenia@umkc.edu
Moulder
J E
JE
Cohen
E P
EP
Fish
B L
BL
Taylor
J M
JM
Veno
P A
PA
Wolfe
L F
LF
Ward
W F
WF
D000450:Aldosterone / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002216:Captopril / Q000627:therapeutic use; D004195:Disease Models, Animal; D004656:Enalapril / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005355:Fibrosis / Q000517:prevention & control*; D007093:Imidazoles / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000517:prevention & control*; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D000450:Aldosterone; C070967:L 158809; D004656:Enalapril; D002216:Captopril