Mizoribine Reduces Urinary Protein Excretion in Rats Given Puromycin Aminonucleoside

1996 ◽  
Vol 16 (2) ◽  
pp. 167-172 ◽  
Author(s):  
T. Shibasaki ◽  
H. Matsuda ◽  
H. Gomi ◽  
M. Usui ◽  
F. Ishimoto ◽  
...  
Keyword(s):  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Puromycin Aminonucleoside ◽  
Protein Excretion

scholarly journals Antioxidants protect podocyte foot processes in puromycin aminonucleoside-treated rats.

1994 ◽  
Vol 4 (12) ◽  
pp. 1974-1986
Author(s):  
S D Ricardo ◽  
J F Bertram ◽  
G B Ryan
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Epithelial Cell ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Alpha Tocopherol ◽  
Puromycin Aminonucleoside ◽  
Glomerular Epithelial Cell ◽  
Protein Excretion ◽  
Scanning Electron

Whether a reduction in urinary protein excretion in rats coadministered puromycin aminonucleoside and antioxidants was associated with a reduction in alterations to glomerular epithelial cell (podocyte) ultrastructure was examined. Daily urinary protein excretion was measured in rats that received a single i.v. injection of saline or puromycin aminonucleoside with or without coadministration of antioxidants. The coadministration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase to puromycin aminonucleoside-treated rats reduced proteinuria by approximately 90, 40, and 60%, respectively, over the 18-day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscopy and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analysis of glomeruli from puromycin aminonucleoside-treated rats coadministered antioxidants revealed significantly reduced foot process effacement on Days, 4, 5, and 10 compared with rats that received puromycin aminonucleoside alone. Thus, at Day 10, puromycin aminonucleoside-treated rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thiourea, or superoxide dismutase contained 90, 74, and 88% (P < 0.01 in all cases) more glomerular epithelial cell filtration slits per unit length of glomerular basement membrane than rats treated with puromycin aminonucleoside alone. In contrast, by scanning electron microscopy, the antioxidants were found to provide no protection against the changes occurring in glomerular epithelial cell bodies and major processes. These results provide further evidence of a role for reactive oxygen species in puromycin aminonucleoside nephrosis and indicate that the antioxidants provide protection against the changes occurring in glomerular epithelial cell foot processes.

scholarly journals Increased cathepsin D-like activity in cortex, tubules, and glomeruli isolated from rats with experimental nephrotic syndrome

1984 ◽  
Vol 223 (2) ◽  
pp. 393-399 ◽  
Author(s):  
W H Baricos ◽  
S V Shah
Keyword(s):  
Nephrotic Syndrome ◽  
Cathepsin D ◽  
Rat Kidney ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Rat Tissues ◽  
Puromycin Aminonucleoside ◽  
Protein Excretion ◽  
Normal Rat ◽  
Functional Areas

We have examined the activity and distribution of cathepsin D (EC 3.4.23.5), a major renal lysosomal endoproteinase, in the various anatomical and functional areas of normal rat kidney. Cathepsin D-like activities (delta A280/h per mg of protein) in normal rat tissues were: cortex, 0.78 +/- 0.05, n = 37; medulla, 0.62 +/- 0.03, n = 12; papilla, 0.63 +/- 0.04, n = 12; tubules, 0.74 +/- 0.04, n = 28; glomeruli, 0.59 +/- 0.03, n = 28; and liver, 0.41 +/- 0.02, n = 28. Enzyme activity was maximal at pH 3.0-3.5 and inhibited more than 90% by pepstatin (6.7 micrograms/ml), suggesting that the enzyme is cathepsin D. In subsequent experiments we measured cathepsin D-like activity in cortex, tubules and glomeruli isolated from rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome. Treated animals (15 mg of PAN/100g body wt., intraperitoneally) developed proteinuria beginning 4 days after injection and exceeding 900 mg/24h on day 9. In two separate experiments involving 52 animals we observed a significant increase in cathepsin D-like activity in cortex (+82.7%), tubules (+109.6%) and glomeruli (+54.7%) isolated from PAN-treated rats killed during marked proteinuria (day 9, mean total urinary protein excretion: 937 +/- 94 mg/24h). This increase was observed whether the activity was expressed per mg of DNA or per mg of protein. Increased cathepsin D-like activity was first observed in cortex and tubules coincident with the onset of proteinurea (day 4, mean total urinary protein excretion: 112 +/- 23 mg/24h). In contrast with the significant elevation of renal cathepsin D-like activity, the activity (nmol/h per mg of protein) of alpha-L-fucosidase (EC 3.2.1.51), a non-proteolytic enzyme, was markedly decreased in the identical samples used for the measurement of cathepsin D-like activity: cortex (-46.4%); tubules (-46.1%); and glomeruli (-38.5%). In addition to changes in renal enzyme activities, PAN-treated rats excreted large amounts of cathepsin D-like activity in their urine (beginning on day 3) compared with nearly undetectable cathepsin D-like activity in the urine from control rats. The significant increases in glomerular and tubular cathepsin D activity may reflect an important role for this enzyme in the pathophysiology associated with PAN-induced nephrotic syndrome.

scholarly journals Osteopontin in chronic puromycin aminonucleoside nephrosis.

1997 ◽  
Vol 8 (9) ◽  
pp. 1383-1390 ◽  
Author(s):  
A B Magil ◽  
R H Pichler ◽  
R J Johnson
Keyword(s):  
Chronic Phase ◽  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Nuclear Antigen ◽  
Renal Diseases ◽  
Monocyte Count ◽  
Puromycin Aminonucleoside ◽  
Protein Excretion ◽  
Aminonucleoside Nephrosis ◽  
Puromycin Aminonucleoside Nephrosis

Increased expression of osteopontin (OPN) associated with interstitial monocyte infiltration has been demonstrated in the early phase of a variety of experimental renal diseases. Whether these changes occur in the chronic phase of progressive glomerular disease is unknown. Chronic puromycin aminonucleoside nephrosis (PAN) was induced in 16 rats by the injection of a single bolus of PA into the internal jugular vein, which results in a triphasic disease characterized by minimal glomerular change and marked proteinuria, peaking at about 10 to 14 d and subsiding by 28 d, followed by a quiescent 4-wk period of no or minimal proteinuria and then the development of progressive focal glomerulosclerosis (FGS) and increasing proteinuria. Fifteen rats injected similarly with normal saline served as controls. At 11 d after injection, PA rats demonstrated significantly greater urinary protein excretion (P = 0.0107), cortical tubular OPN expression (P = 0.0086), and intraglomerular (P = 0.0009) and interstitial (P = 0.0212) monocyte infiltration than did the controls. At 42 d, no significant differences between the two groups with respect to the above parameters were detected. At 98 d, PA rats had FGS and showed a definite trend to increased proteinuria, cortical tubular OPN, and intraglomerular monocyte infiltration. Although the cortical interstitial monocyte count was not elevated in PA rats compared with controls, there were significantly more monocytes around OPN-positive cortical tubules than around OPN-negative ones (P = 0.0011). Cortical tubular OPN expression correlated well with urinary protein excretion (r = 0.932, P < 0.0001), cortical tubular proliferating cell nuclear antigen (r = 0.796, P < 0.0001), and intraglomerular monocyte count (r = 0.552, P = 0.0013). The results are consistent with a monocyte chemoattractant role for OPN and suggest that OPN is upregulated in the chronic phase of PAN and that this increase in expression is a result of glomerular events.

Patterns of Urinary Protein Excretion in Patients with Sepsis

Nephron ◽  
1982 ◽  
Vol 31 (3) ◽  
pp. 219-223 ◽  
Author(s):  
John M. Richmond ◽  
William J. Sibbald ◽  
Anne M. Linton ◽  
Adam L. Linton
Keyword(s):  
Urinary Protein Excretion ◽  
Urinary Protein ◽  
Protein Excretion
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