Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycophenolate mofetil (MMF) is a new immunosuppressive drug whose active metabolite, mycophenolic acid (MPA), blocks the action of inosine monophosphate dehydrogenase, resulting in the inhibition of the novo purine synthesis. Thus, MPA has an antiproliferative effect on T and B lymphocytes and also inhibits the glycosylation of cell surface adhesion proteins involved in cell-cell contact and in the recruitment of circulating leukocytes to sites of tissue damage and inflammation. In this study, the effect of MMF in the mercury model of nephritis was examined. Repeated exposure to HgCl(2) induces an autoreactive Th2 cell subset-inducing polyclonal B cell activation in the Brown Norway (BN) rat. This leads to the development of an autoimmune syndrome characterized by synthesis of autoantibodies (mainly anti-glomerular basement membrane [GBM] Abs) with glomerular linear deposits of IgG, proteinuria, and tubulointerstitial nephritis. Results show that MMF has a preventive effect on mercury-induced disease as it blocks anti-GBM Ab synthesis, thus avoiding glomerular IgG deposits and proteinuria and the development of interstitial nephritis. However, the therapeutic effect of MMF seems to be restricted to its antiinflammatory properties blocking the extravasation of circulating leukocytes to renal interstitium by interfering with the very late activation antigen 4/vascular cell adhesion molecule-1 (VCAM-1) cell adhesion pathway. Also, MMF administration to mercury-injected rats reduces the secretion of the proinflammatory cytokine tumor necrosis factor-alpha. These findings confirm that MMF has a strong effect on the primary immune response in this model. Nevertheless, when the disease is in progress, MMF acts exclusively on the inflammatory response. MMF could be useful in the treatment of diseases associated with renal inflammation.
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PMID:Effects of mycophenolate mofetil in mercury-induced autoimmune nephritis. 1191 53

FK778 blocks the dihydro-orotate dehydrogenase, necessary for pyrimidine synthesis, and mycophenolate mofetil (MMF) inhibits the inosine monophosphate dehydrogenase, a crucial enzyme for purine biosynthesis. Beneficial immunosuppressive effects have been suggested for the combination of both drugs. The Brown Norway-Lewis rat heterotopic heart transplantation model was used. FK778 (5 and 20 mg/kg/day), MMF (10 and 40 mg/kg/day), or a combination of both drugs for 10 days was used for prevention of acute graft rejection. Grafts of untreated animals were rejected after 6.2 +/- 0.4 days. Low-dose FK778 and low-dose MMF administration did not result in a significantly prolonged graft survival (6.7 +/- 0.8 and 8.7 +/- 1.4 days; P=not significant). Grafts of rats treated with high-dose FK778 or high-dose MMF survived significantly longer (17.0 +/- 2.8 and 20.7 +/- 3.8 days; P<0.01). Concomitant use of low-dose FK778 with low-dose MMF produced synergistic interactions (mean survival time 12.3 +/- 2.9 days; P<0.01; combination index=0.85). High-dose drug combination (mean survival time 24.0 +/- 1.4 days) showed antagonistic drug interaction (combination index=1.55) with increased toxic side effects.
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PMID:Immunosuppression with FK778 and mycophenolate mofetil in a rat cardiac transplantation model. 1470 37

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.
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PMID:Mycophenolate mofetil prevents autoimmune glomerulonephritis and alterations of intrarenal adrenomedullin in rats. 1506 64