Open AccessAminoguanidine reduces glomerular inducible nitric oxide synthase (iNOS) and transforming growth factor‐beta 1 (TGF‐β1) mRNA expression and diminishes glomerulosclerosis in NZB/W F 1 mice
Author(s) -
Chen Yang,
Yu Cc,
Ko Yc,
ChienChia Huang
Publication year - 1998
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1998.00632.x
Subject(s) - nitric oxide synthase , glomerulosclerosis , transforming growth factor beta , transforming growth factor , endocrinology , medicine , messenger rna , nitric oxide , beta (programming language) , tgf beta signaling pathway , biology , gene expression , immunology , proteinuria , gene , kidney , biochemistry , computer science , programming language
Over‐expression of iNOS is implicated in the pathogenesis of glomerulonephritis in animal models of systemic lupus erythematosus. The aim of this study was to evaluate the effect of aminoguanidine, a selective inhibitor of iNOS, for the protection from glomerulosclerosis in NZB/W F 1 mice. Female NZB/W F 1 mice ( n = 8) were treated with aminoguanidine (1 g/ l ) in drinking water for 4 months starting at age 2 months before the onset of glomerulonephritis. Controls were age‐ and sex‐matched mice ( n = 10) without aminoguanidine treatment. By glomerular microdissection and reverse‐transcription competitive polymerase chain reaction, we found that glomerular iNOS/β‐actin and TGF‐β1/β‐actin mRNA ratios were reduced 15.1% ( P < 0.05) and 61.3% ( P < 0.01), respectively, in aminoguanidine‐treated mice. Aminoguanidine significantly reduced the glomerular iNOS staining, urinary nitrite production and degree of glomerulosclerosis. In addition, the glomerular volume and mean glomerular cell number were reduced 33.2% ( P < 0.01) and 32.8% ( P < 0.01), respectively. Likewise, the urinary proteinuria was also significantly reduced by aminoguanidine. These results indicate that administration of aminoguanidine may reduce the progression of glomerulosclerosis in NZB/W F 1 mice, possibly through inhibition of glomerular nitric oxide production.