Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of YM264, WEB2086, methylprednisolone and ticlopidine on puromycin-induced nephropathy in the rat. Puromycin produces marked proteinuria, hypercholesterolemia, and hypoalbuminemia. The structurally differing PAF antagonists YM264 and WEB2086 inhibited proteinuria and improved hypercholesterolemia and hypoalbuminemia. Methylprednisolone also exhibited a beneficial effect on these variables. However, ticlopidine, a platelet inhibitor, showed no inhibitory effect on nephropathy. These results indicate that PAF may play a major role in puromycin-induced nephropathy in the rat, and that PAF antagonists may prove of therapeutic value in the treatment of nephropathy in humans.
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PMID:Effects of YM264, a novel PAF antagonist, on puromycin aminonucleoside-induced nephropathy in the rat. 202 90

Sprague-Dawley rats injected with a single dose of adriamycin at 7.5 mg/kg/day developed an important and persistent proteinuria from day 14. Animals treated from day 0 to 3 weeks with PAF-receptor antagonists (BN 52021 or alprazolam) did not present (p less than 0.0005) the adriamycin-induced proteinuria or only to a very low extent. Furthermore, epithelial glomerular cells presented in these animals a normal aspect, while in rats injected with adriamycin, but not treated, the epithelial cells showed effacement of foot processes and intensive degenerative changes. By contrast, rats treated with steroids or cyclosporin did not present a significant reduction in proteinuria or improvements in epithelial cell lesions. Rats injected with adriamycin also presented an increase in the number of inflammatory infiltrating cells, chiefly la(+)-reactive cells (OX6+ cells), macrophages (ED1+ cells) and T-cytotoxic/suppressor cells (OX8+ cells). Concomitant administration of PAF-receptor antagonists induced a significant reduction in the number of these cells. Glomerular cells from normal control rats incubated with adriamycin incorporated 3H-acetate into a polar lipid with biological and migratory characteristics on thin-layer chromatography similar to synthetic PAF. On the whole, our data suggest a role for PAF in the pathogenesis of experimental nephrotic syndrome induced by adriamycin.
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PMID:Evidence suggesting a role for platelet-activating factor (PAF) in experimental nephrotic syndrome. 217 55

Rats receiving a single injection of either aminonucleoside of puromycin (PAN, 10 mg/100 g) or Adriamycin (ADR, 7.5 mg/kg) develop heavy proteinuria and tubulointerstitial nephritis. Interstitial mononuclear cells were markedly more intense in PAN- than in ADR-treated rats. The composition of cell infiltrates was characterised in frozen kidney sections using an immunoperoxidase staining method and a panel of specific monoclonal antibodies. The severe mixed cellular lesions observed in the PAN model on day 14 were dominated by ED1+ macrophages, OX6+ Ia-interstitial and OX8+ T-cytotoxic/suppressor cell surface markers. A similar but more discrete ADR-interstitial cell accumulation was observed on day 11 of the experiment. A correlation existed in the PAN model between the severity of interstitial nephritis and the degree of proteinuria. In contrast, there was no such correlation in ADR nephrosis. Administration of PAF antagonist (BN 52021), started on the first day and continued throughout the 4 weeks of the experiment, induced in both ADR and PAN-treated rats a partial reduction in the number of interstitial cell infiltrates. Glomeruli from normal control rats incubated with 3H acetate, substrate for lyso-PAF: acetyl-CoA acetyltransferase and ADR stimulated PAF generation. Although the precise mechanism of interstitial cell accumulation in these two models of nephrosis are still unknown, our results suggest that PAF could be an important factor involved in interstitial cell recruitment.
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PMID:Interstitial mononuclear cell infiltrates in experimental nephrosis: effect of PAF antagonist. 251 24

The effect of steroids, heparin and specific PAF-acether antagonists (BN 52021 and triazolobenzodiazepines) on proteinuria and renal histological changes induced in rats by adriamycin was studied. Adriamycin evoked a marked proteinuria that was unaffected by methylprednisolone and slightly reduced by heparin. In contrast, adriamycin-injected rats treated with PAF-acether antagonists had a low proteinuria, if any, and no ultrastructural glomerular alterations. These data suggest that PAF-acether could play a major role in the occurrence of proteinuria and that PAF-acether antagonists might provide a new therapeutic approach in certain human nephropathies.
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PMID:Role of platelet-activating factor in adriamycin-induced nephropathy in rats. 362 4

Serum sickness was induced in rats by a modification of previously described methods avoiding i.v. administration of the antigen. All the animals developed a progressive disease characterized by an initial pattern of deposition of IC in the mesangium followed by the appearance of GBM deposits. This change in the deposition of IC was associated with the onset of massive proteinuria and a fall in the titre of precipitating antibodies. Simultaneously, specific desensitization of platelets for a rat PAF could be demonstrated and platelet aggregates were seen in the glomeruli. The presence of homocytotropic IgGa anti-ovalbumin antibodies in rat sera during the induction of the disease was demonstrated by 2 hr PCA. Accordingly, this antibody together with the antigen ovalbumin induced the release of histamine from peritoneal mast cells, suggesting that a similar mechanism might occur in vivo during the induction of the disease. Rat PAF and beta glucuronidase could be obtained from peritoneal macrophages under similar conditions to those required for the release of histamine. The data support a role for inflammatory mediators in the increase in vascular permeability needed for the deposition of IC in the GBM and provide evidence for a new role of macrophages and PMNs in glomerular pathology in contributing to an increase in permeability of GBM.
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PMID:Rat serum sickness: possible role of inflammatory mediators allowing deposition of immune complexes in the glomerular basement membrane. 717 98

We have studied the effect of therapy with plasma FN on glomerular synthesis of PAF, TNF-alpha and FN, in experimental proliferative glomerulonephritis. Glomerular PAF, TNF-alpha and FN production were increased in rats with nephritis. Peak glomerular PAF production preceded, while peak glomerular TNF-alpha bioactivity coincided with maximal proteinuria. Rats treated with FN (5 mg/kg per 48 h) for 15 days had less proteinuria, glomerular and interstitial cell infiltration and glomerular PAF, TNF-alpha and FN synthesis than non-treated rats. In order to characterize further the mechanisms of action of FN, healthy rats were injected with either FN or saline. Peripheral blood mononuclear cells and neutrophils from healthy rats injected with FN secreted less TNF-alpha and PAF, respectively, than those obtained from saline-treated rats. Our data suggest that the beneficial effect of FN may be related to decreased number of glomerular leucocytes and decreased synthesis of inflammatory mediators and extracellular matrix.
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PMID:Fibronectin (FN) decreases glomerular lesions and synthesis of tumour necrosis factor-alpha (TNF-alpha), platelet-activating factor (PAF) and FN in proliferative glomerulonephritis. 764 18

An unresolved question of many medical nephropathies is the progression of chronic renal failure to end-stage renal insufficiency: every year many patients must be submitted to extracorporeal haemodialysis with a high cost for society. The control of so-called risk factors of progression, such as arterial hypertension, persistent proteinuria, renal infection etc. is not sufficient to prevent the progression to end-stage renal failure. The hypoproteic diet may retard this progression So currently the ability of physicians to alter the inexorable course of the disease is limited. In recent years medical research has shown that many mediators of phlogosis may play an important role in renal glomerular pathology. PAF seems to have a preeminent role. The aim of this study is to present the actual knowledge about the role played by PAF in renal physiology and pathophysiology with future perspectives on renal insufficiency progression.
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PMID:[Progression of renal insufficiency and platelet activating factor (PAF)]. 870 Mar 58