Mycophenolate mofetil prevents autoimmune glomerulonephritis and alterations of intrarenal adrenomedullin in rats.
We studied the effects of mycophenolate mofetil, a specific inhibitor of inosine monophosphate dehydrogenase, on the mercuric chloride induced autoimmune glomerulonephritis in Brown Norway rats and also on the renal contents of adrenomedullin. In the rats with autoimmune glomerulonephritis, plasma and renal tissue adrenomedullin levels were increased significantly. Coadministration of mycophenolate mofetil resulted in prevention of autoimmune glomerulonephritis and also in maintaining of plasma and renal tissue adrenomedullin levels at control levels. Adrenomedullin mRNA expressions in the renal cortex were also higher in the rats with autoimmune glomerulonephritis. Significant positive correlations were found between renal cortical adrenomedullin levels and urinary Na+ and N-acetyl-beta-D-glucosaminidase excretion. A significant negative correlation between renal cortical adrenomedullin levels and creatinine clearance was also found. These results suggest that mycophenolate mofetil suppresses the renal damage in rats with autoimmune glomerulonephritis and renal adrenomedullin may participate in the pathophysiology of autoimmune glomerulonephritis.
Shi
Yi
Y
Department of Urology, Osaka University School of Medicine, Japan.
Yoshihara
Fumiki
F
Nakahama
Hajime
H
Goto
Rieko
R
Sada
Masaharu
M
Kawano
Yuhei
Y
Moriyama
Toshiki
T
Yazawa
Koji
K
Ichimaru
Naotsugu
N
Takahara
Shiro
S
Kangawa
Kenji
K
D053607:Adrenomedullin; D000818:Animals; D015152:Blotting, Northern; D015432:Glomerulonephritis, Membranoproliferative / Q000473:pathology / Q000517:prevention & control*; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000378:metabolism*; D011507:Proteinuria / Q000188:drug therapy; D011687:Purines / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011914:Rats, Inbred BN
D007166:Immunosuppressive Agents; D010455:Peptides; D011687:Purines; D053607:Adrenomedullin; D008627:Mercuric Chloride; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid