Related Experiment Videos
Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats
Abstract:
The aminonucleoside of puromycin induces proteinuria and renal damage when given to rats. Aminonucleoside of puromycin was administered to male Wistar-Furth rats as a single intravenous injection in a dose of 15 mg. per 100 gm. of body weight. The animals were studied 9 days later when the mean urinary protein was 175 mg. per 24 hours. Evidence of glomerular epithelial cell injury included massive obliteration of foot processes, appearance of microvilli, protein reabsorption droplets, extreme attenuation of cytoplasm with formation of blebs, and focal detachment of epithelial cells from glomerular basement membrane. An increase in both the amount of mesangial matrix and the number of mesangial cells was also observed. The fractional clearance (C/GFR) of anionic horseradish peroxidase had increased 18.5 times as compared to control values and was nearly equal to the C/GFR of neutral horseradish peroxidase in the experimental rats. The C/GFR of cationic horseradish peroxidase was decreased by one-third so that it approximated the C/GFRs of both anionic and neutral horseradish peroxidase. These findings indicate a nearly complete loss of the charge-selective barrier to filtration. In addition, C/GFRs of tritiated uncharged dextrans with a range of molecular radii from 18 to 58 Angstrom (A) were determined. The C/GFRs of dextrans (alpha e less than 30 A) were decreased in the experimental rats as compared to C/GFRs of dextrans of corresponding molecular size in control rats. However, the C/GFRs of dextrans (alpha e greater than 38A) were increased in experimental as compared to control rats. Further, both anionic and cationic ferritin (alpha e = 61 A) were observed in the urinary space near denuded areas of glomerular basement membrane. These results indicate that the size-selective properties of the glomerular barrier to filtration have been modified with decreased C/GFR of small molecules and increased C/GFR of large molecules. Thus, the proteinuria of aminonucleoside nephrosis in rats occurs secondary to alterations in both the charge- and size-selective barriers to glomerular filtration.
Insights
Puromycin aminonucleoside causes kidney damage and proteinuria in rats by altering glomerular filtration barriers. This study reveals significant changes in both charge- and size-selective properties of the kidney filter.
Area of Science:
- Nephrology
- Renal Physiology
- Pathology
Background:
- Puromycin aminonucleoside is a known nephrotoxic agent.
- Aminonucleoside nephrosis is characterized by proteinuria and renal damage.
Purpose of the Study:
- To investigate the effects of puromycin aminonucleoside on the glomerular filtration barrier in rats.
- To elucidate the mechanisms underlying proteinuria in aminonucleoside-induced nephrosis.
Main Methods:
- Male Wistar-Furth rats were administered a single intravenous dose of puromycin aminonucleoside.
- Urinary protein levels were measured 9 days post-injection.
- Fractional clearance of various tracers (horseradish peroxidase, dextrans, ferritin) was assessed to evaluate glomerular barrier function.
Main Results:
- Puromycin aminonucleoside induced significant proteinuria (175 mg/24 hours).
- Glomerular injury included foot process effacement and epithelial cell damage.
- Loss of charge selectivity was evidenced by altered horseradish peroxidase clearance.
- Changes in dextran and ferritin clearance indicated modifications in size-selective properties.
Conclusions:
- Puromycin aminonucleoside nephrosis results from damage to both charge- and size-selective barriers of the glomerulus.
- These alterations lead to a near-complete loss of glomerular charge selectivity and modified size selectivity.
- The study provides insights into the pathogenesis of drug-induced kidney damage and proteinuria.