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Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0033687 (
proteinuria
)
24,015
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Proteinuria
and renal xanthine metabolising enzymes, xanthine oxidase and
xanthine dehydrogenase
, were evaluated in Adriamycin-treated rats fed standard (21% casein) and low-protein (6% casein) diets. In rats fed a standard diet Adriamycin was associated with increased activities in the kidney of xanthine oxidase and
xanthine dehydrogenase
and induced massive
proteinuria
. The pharmacological block of both enzymes by allopurinol and tungsten block of both enzymes by allopurinol and tungsten reduced
proteinuria
to one-third of the original levels. Rats fed a low-protein diet presented decreased levels of renal xanthine oxidase and
xanthine dehydrogenase
and were only slightly proteinuric. Finally, rats shifted from a low-protein diet to a normal one developed massive
proteinuria
in spite of normal or slightly decreased levels of renal xanthine oxidase and
xanthine dehydrogenase
. We conclude that a low-protein diet is effective in decreasing the levels of xanthine metabolising enzymes that are in part responsible for the renal damage due to Adriamycin. This is not however the unique mechanism by which the low-protein diet protects against the development of
proteinuria
in Adriamycin nephrosis; other factors must also be hypothesised.
...
PMID:Low-protein diet and xanthine-metabolising enzymes in adriamycin nephrosis. 212 63
1. The hypothesis was tested that the renal xanthine oxidase system provides a source of oxygen free radicals in puromycin aminonucleoside and adriamycin experimental nephrosis by generating uric acid from hypoxanthine and xanthine. 2. The concentrations in renal tissue of the putative intermediary products of puromycin aminonucleoside metabolism, hypoxanthine and xanthine, and of their precursors, adenosine and inosine, were lower in rats treated with puromycin aminonucleoside than in normal controls, whereas concentrations of the metabolites were normal after adriamycin intoxication. Their daily urinary excretion was lower in the 24 h after puromycin aminonucleoside administration compared with the baseline values and returned to near normal levels within 5 days. After adriamycin the 24 h urinary excretion of xanthine and uric acid was double the baseline levels (P less than 0.001). 3. When equimolar amounts of hypoxanthine were injected instead of puromycin aminonucleoside, the concentration of all bases increased slightly in renal tissue and their urinary efflux was double the baseline level: allantoin, uric acid, the unmodified nucleotide and xanthine were the most represented compounds in urine. 4. The enzymatic activities relative to xanthine oxidase (EC 1.1.3.22) and
xanthine dehydrogenase
(EC 1.1.1.204) in renal tissues were unchanged 1 day after puromycin aminonucleoside or hypoxanthine intoxication and only moderately increased in both groups at 13 days (the time of appearance of heavy
proteinuria
in the puromycin aminonucleoside-treated group). In contrast, xanthine oxidase and
xanthine dehydrogenase
activities were higher in adriamycin-treated rats at 1 and 15 days after the treatment (P less than 0.001). 5. Feeding rats with normoprotein diets containing tungsten induced a marked and constant decrease of renal xanthine oxidase and
xanthine dehydrogenase
activities to 20% of the baseline values in both puromycin aminonucleoside- and adriamycin-treated rats. Inhibition of renal xanthine oxidase and
xanthine dehydrogenase
activities by tungsten was associated with a marked reduction (P less than 0.001) of
proteinuria
in adriamycin-treated rats and the same occurred with allopurinol, a specific inhibitor of xanthine oxidase activity. In contrast, tungsten treatment did not reduce the
proteinuria
associated with puromycin aminonucleoside, which reached a maximum 13 days after puromycin aminonucleoside intoxication. Hypoxanthine-treated rats were normoproteinuric after 2 months of observation. 6. These data demonstrate an activation of renal xanthine oxidase and
xanthine dehydrogenase
after adriamycin intoxication which is relevant to the induction of
proteinuria
. They also argue against the involvement of the renal xanthine oxidase system as a source of free radicals in puromycin aminonucleoside nephrosis and suggest that the nucleotide cycle is not a normal route for puromycin aminonucleoside degradation.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Renal purine efflux and xanthine oxidase activity during experimental nephrosis in rats: difference between puromycin aminonucleoside and adriamycin nephrosis. 215 48
The role of xanthine oxidase as a source of reactive oxygen species in puromycin aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and
xanthine dehydrogenase
activity, and urinary protein excretion were examined in puromycin aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced
proteinuria
by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared to rats that received puromycin aminonucleoside alone. Unexpectedly, co-administration of allopurinol to puromycin aminonucleoside-treated rats did not reduce xanthine oxidase activity; however, the combined activity of xanthine oxidase and
xanthine dehydrogenase
in such animals was reduced on day 5. Co-administration of tungsten to puromycin aminonucleoside-treated rats did not reduce
proteinuria
or alter the number of filtration slits. Rats co-administered tungsten and puromycin aminonucleoside had significantly reduced renal xanthine oxidase and combined xanthine oxidase and
xanthine dehydrogenase
activities on days 5 and 10, compared to rats treated with puromycin aminonucleoside alone. These results provide evidence that the protection provided by allopurinol in puromycin aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.
...
PMID:Podocyte architecture in puromycin aminonucleoside-treated rats administered tungsten or allopurinol. 758 48
Passive Heymann nephritis (PHN) in rats is a model of human membranous nephropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have been implicated in the subsequent glomerular damage which leads to
proteinuria
. This study examines the involvement of xanthine oxidase in this process. Xanthine oxidase activity was increased nearly twofold in glomeruli isolated 1 and 12 d after induction of PHN, and this was associated with increased glomerular superoxide anion generation. Analysis of glomerular samples by Northern and Western blotting revealed no quantitative changes in xanthine oxidoreductase expression in PHN, suggesting conversion of
xanthine dehydrogenase
to the oxidase form as the cause of increased activity. Treatment of rats with tungsten, an inhibitor of xanthine oxidase, before induction of PHN resulted in a marked decrease in glomerular xanthine oxidase activity and superoxide anion generation, and decreased
proteinuria
by 80% (day 12: 423+/-245 mg/d in PHN versus 78+/-53 mg/d in tungsten-treated PHN animals, P < 0.01). These findings point to a pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of importance in the therapy of human membranous nephropathy.
...
PMID:Role of xanthine oxidase in passive Heymann nephritis in rats. 1007 4
Adenine phosphoribosyltransferase deficiency is a rare, inherited autosomal recessive disease presenting with 2,8-dihydroxyadenine (DHA) urolithiasis, DHA nephropathy, and chronic kidney disease. The presence of DHA crystals in urine and renal biopsy is pathognomonic of the disease. We report a 23-year-old female with acute renal failure and nephrotic
proteinuria
. Urinalysis showed reddish brown, round crystals with dark outline, and central spicules consistent with 2,8-DHA crystals. Renal biopsy showed membranous nephropathy and 2,8-DHA nephropathy. Our patient improved with liberal fluid intake, restriction of high adenine content foods, and oral
xanthine dehydrogenase
inhibitor febuxostat. Early diagnosis and initiation of treatment prevent renal complications.
...
PMID:Unusual cause of crystalline nephropathy. 2965 21
