Experimental Nephrotic Syndrome Induced in Rats by Aminonucleoside. Renal Lesions and Body Electrolyte Composition.

Frenk, Silvestre; Antonowicz, Irena; Craig, John M.; Metcoff, Jack

doi:10.3181/00379727-89-21833

Cited by 185 publications

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“…Puromycin aminonudeoside induces in rats a characteristic renal syndrome that resembles human lipoid nephrosis in many respects (14,15): clinically there are massive proteinuda, edema, and hypercholesterolemia, and ultrastructurally the glomeruli show alterations in the epithelial cells, with relatively normal basement membranes (5). Although the mechanism by which aminonudeoside induces this effect is still unknown, the experimental model has been used extensively to study a variety of biochemical, immunological, and morphological events in the nephrotic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Glomerular Permeability

Venkatachalam

Karnovsky

Cotran

1969

The Journal of Experimental Medicine

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Massive proteinuria is one of the major manifestations of the nephrotic syndrome and results in hypoproteinemia, decreased colloid osmotic pressure, and edema. In spite of considerable investigation, the mechanism of proteinuria in the nephrotic syndrome remains poorly understood.The available evidence suggests that increased glomerular permeability rather than tubular secretion or dimlnlghed tubular reabsorption is the cause of protein loss (1-3), but the ultrastructural and biochemical bases for glomerulax leakage have not been clearly identified. Studies employing ferritin as an electron microscope tracer (4, 5) have suggested that the glomerular basement membrane is the normal filtration barrier to this large protein, and that increased basement membrane permeability can account for proteinuria in experimental aminonucleoside nephrosis. In the ferritin studies only small amounts of tracer escaped into the urinary space; thus the mechanism of prorein transfer across the glomerular epithelium was not clarified. It is the glomerular epithelium that undergoes the most significant fine structural changes in human lipoid and experimental aminonudeoside nephrosis.The availability of sensitive ultrahistochemical methods for locafization of enzyme tracers of different molecular weights (6--8) has prompted us to reexamine the ultrastructural events in the nephrotic syndrome with the use of such tracers. In the present paper we report on the localization of horseradish peroxidase, a relatively small molecular weight protein (mol wt 40,000) which passes freely across the basement membrane (7) and thus can be used to study the mode of transepithelial passage of leaking proteins.

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Section: Discussionmentioning

confidence: 99%

Glomerular Permeability

Venkatachalam

Karnovsky

Cotran

1969

The Journal of Experimental Medicine

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“…Nephrosis was produced in male Sprague Dawley albino rats which weighed 150-200 g by the intravenous administration of 100 mg/100 g, body wt, of an aminonucleoside of puromycin, 6-dimethyl-9-(3'-amino-3'-deoxy-^jD ribofuranosyl purine [7,13]. Micropuncture experiments were carried out on 17 animals 96 and 144 hr after the injection of aminonucleoside and in 5 animals 4 days after the intravenous injection of saline (controls).…”

Section: Methodsmentioning

confidence: 99%

Micropuncture Study of Albumin Transfer in Aminonucleoside Nephrosis in the Rat

Lewy

Pesce

1973

Pediatr Res

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ExtractAlbumin concentration in the proximal tubules of normal rats and rats with aminonucleoside nephrosis (AMN) was estimated by means of a sensitive radioimmunoassay. Nephrotic animals were studied at the onset of proteinuria and when the nephrotic syndrome was fully established. Albumin concentration in the proximal tubule of normal male rats averaged 2.5 ± 0.3 mg/100 ml, whereas in early nephrotic rats it averaged 4.9 ± 1.3 mg/100 ml and in normal sized tubules of heavily proteinuric rats, 15.7 ± 3.3 mg/100 ml. Control and early AMN animals appeared to have a relatively homogeneous population of surface convolutions, whereas the fully nephrotic rats had markedly increased heterogeneity. A population of dilated proximal tubules with an albumin concentration of 233.8 ± 35.4 mg/100 ml was found in this group. Albumin concentrations were randomly distributed throughout the proximal convolution of all three groups with no clear pattern of changing concentration along the nephron. The data demonstrate that enhanced glomerular permeability to albumin occurs in the experimental nephrotic syndrome in the rat. Speculation

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“…An enhanced proximal tubule sensitivity to gentamycin has been demonstrated in rats with polyvinyl alcohol-induced benign glomerulopathy (10) as well as in acute canine nephrotoxic glomerulonephritis (57,58). These (3,20,54) in susceptible species such as rats and rabbits. Hexachloro-1:3-butadiene (HCBD) was selected to produce a discrete lesion characterized by necrosis of the straight portion (pars recta) of the proximal tubule (2,39).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Hexachloro-1:3-butadiene Nephrotoxicity in Rats with a Preexisting Adriamycin-Induced Nephrotic Syndrome

Kirby

Bach

1995

Toxicol Pathol

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Renal damage was assessed by histopathology and urinalysis in male Wistar rats treated with either hexachloro-1:3-butadiene (HCBD; a single 170-mg/kg ip dose that caused proximal tubule necrosis), adriamycin (ADR; a single 5-mg/kg ip dose that caused minimal glomerular changes up to 35 days), or HCBD given 2 wk after ADR and compared with age-matched control rats for 21 days. Urinalysis values in ADRtreated rats showed minimal renal changes. HCBD significantly elevated urine volume (10-fold), protein (5-fold), glucose (175-fold), and brush border enzymes (10-600-fold), indicating severe proximal tubular damage, but most parameters returned to pretreatment levels 6 days after treatment. In ADR-pretreated rats subsequently given HCBD, both the urinary alkaline phosphatase and the ratio of kidney : body weight were significantly higher for longer periods. Histopathology demonstrated that the HCBD-induced proximal tubular lesion was confined to the outer stripe of the outer medulla. Advanced regeneration and repair was evident 21 days after HCBD treatment. In the ADR-pretreated rats the HCBD-induced lesion was more severe and affected the entire cortex (24).Statistics. Statistically significant differences between groups were determined by 2-tailed Students' t-test, with p < 0.05 considered to be statistically significant. RESULTS UrinanalysisThere were no significant differences in the urinary parameters in the control and ADR groups ( (Fig. 1 a). Tubules were dilated and filled with homogenous eosinophilic material and necrotic epithelial cells. Signs of regeneration and restitution (i.e., tubular re-epithelialization and loss of tubular casts and debris) were evident by day 7 and complete 21 days after treatment (Fig. 1 b).Histologically, animals in the ADR/HCBD group showed much more extensive renal damage (Fig. 2a) when compared to those treated with HCBD alone (see Fig. 1 a). Extensive tubular damage was present throughout the entire cortex 2 days after HCBD treatment, and tubules were dilated and filled with homogeneous proteinaceous material. Sloughed necrotic calcified epithelial cells were observed in tubular lumens and casts extended deep into the medulla (Fig. 2b). Extensive calcification was evident by day 7 (which was not seen in the HCBD only group) and by day 21, regeneration, although apparent, was less advanced and marked tubular calcification was still evident (Fig. 2c). Table 2 summarizes the differences between the ADR/HCBD group and HCBD alone. HistochemistryControl kidneys demonstrated normal GGT staining of the tubular epithelium of the outer stripe of the outer medulla (Fig. 3a). ADR caused no changes in this staining pattern. GGT staining in the outer stripe of the outer medulla was diminished 24 hr after HCBD treatment, was barely evident by day 3 (Fig. 3b) HCBD is a useful model toxin for damaging the proximal tubule. It is metabolized in the liver, ex-

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Experimental Nephrotic Syndrome Induced in Rats by Aminonucleoside. Renal Lesions and Body Electrolyte Composition.

Cited by 185 publications

References 0 publications

Glomerular Permeability

Glomerular Permeability

Micropuncture Study of Albumin Transfer in Aminonucleoside Nephrosis in the Rat

Enhanced Hexachloro-1:3-butadiene Nephrotoxicity in Rats with a Preexisting Adriamycin-Induced Nephrotic Syndrome

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