Aminoguanidine reduces glomerular inducible nitric oxide synthase (iNOS) and transforming growth factor-beta 1 (TGF-beta1) mRNA expression and diminishes glomerulosclerosis in NZB/W F1 mice.
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 F1 mice. Female NZB/W F1 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/beta-actin and TGF-beta1/beta-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 F1 mice, possibly through inhibition of glomerular nitric oxide production.
Yang
C W
CW
Division of Nephrology, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China.
Yu
C C
CC
Ko
Y C
YC
Huang
C C
CC
D000818:Animals; D001835:Body Weight; D002452:Cell Count; D003401:Creatine / Q000097:blood / Q000652:urine; D003433:Crosses, Genetic; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D006984:Hypertrophy; D007678:Kidney Glomerulus / Q000473:pathology*; D008181:Lupus Nephritis / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000652:urine; D009929:Organ Size; D011507:Proteinuria; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D004791:Enzyme Inhibitors; D006146:Guanidines; D009573:Nitrites; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D003401:Creatine; C004479:pimagedine