Agmatine inhibits cell proliferation and improves renal function in anti-thy-1 glomerulonephritis.
Changes in the expression of alternate arginine metabolic pathways have been implicated in the pathogenesis of experimental glomerulonephritis. Agmatine, decarboxylated arginine, has been shown in vitro to suppress both inducible nitric oxide synthase and the rate-limiting enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC). This study was undertaken to determine whether agmatine administration could reduce tissue injury by decreasing nitric oxide, and reduce cell proliferation, by diminishing ODC activity, in experimental mesangial proliferative glomerulonephritis (Thy-1 nephritis). Agmatine treatment (50 mg/kg per d intraperitoneally) in Thy-1 nephritis rats prevented a reduction in GFR at day 1. Agmatine treatment decreased nitric oxide production in Thy-1 nephritis rats by 23% and 41% at days 1 and 4, respectively. Agmatine treatment also reduced ODC activity and glomerular (3)H-thymidine incorporation on days 1, 4, and 7. Histologic evaluation revealed a decline in mesangial cell proliferation and extracellular matrix accumulation associated with agmatine treatment administered before or 24 h after Thy-1 antibody, and this was confirmed by a reduction in the number of cells expressing proliferating cell nuclear antigen on days 4 and 7. These studies provide the first in vivo evidence that agmatine administration can reduce cellular proliferation in Thy-1 nephritis and attenuate the initial reduction in renal function associated with this model.
Ishizuka
Shunji
S
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Cunard
Robyn
R
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Poucell-Hatton
Siria
S
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Wead
Lucinda
L
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Lortie
Mark
M
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Thomson
Scott C
SC
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Gabbai
Francis B
FB
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Satriano
Joseph
J
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
Blantz
Roland C
RC
Division of Nephrology-Hypertension and Pathology, University of California, Department of Medicine, San Diego, and VA San Diego Healthcare System, La Jolla, California.
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D009573:Nitrites / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D009994:Osmolar Concentration; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018800:Thy-1 Antigens / Q000276:immunology*
D009573:Nitrites; D018800:Thy-1 Antigens; D000376:Agmatine; D009955:Ornithine Decarboxylase; D006152:Cyclic GMP