Modifications in glomerular polyanion distribution in adriamycin nephrosis.
Previous reports have suggested that, in proteinuria induced by adriamycin (ADR), the functional size barrier of the glomerular basement membrane (GBM) is altered as the result of a sieving defect, whereas the functional charge barrier of the glomeruli remains intact. The aim of this study was to reevaluate the effect of ADR on anionic constituents in the glomerular capillary wall (GCW). Kidneys of nephrotic rats, induced by the injection of 7.5 mg/kg ADR, and controls were resected, and cortices were isolated 24 h and 10 days postinjection, fixed with formaldehyde, and embedded in paraffin. For the histochemical evaluation of sialyl residues, deparafinized sections were treated with biotin-labeled peanut agglutinin (PNA), before or after neuraminidase treatment. PNA binding was visualized by the avidin-biotin-peroxidase complex and interacted with hydrogen peroxide and diaminobenzidine. For electron microscopy, kidney cortices were fixed with glutaraldehyde and embedded in araldite or LR-white. The postembedding localization of anionic sites was carried out by cationic colloidal gold (CCG), directly applied on thin LR-white sections. Although in the 24-h ADR group, kidney functions and glomerular morphology were generally unaltered, the 10-day ADR group exhibited severe proteinuria, hypoalbuminemia, and massive fusion of intercalated foot processes of the podocytes. Intense PNA binding was observed after neuraminidase treatment in the GCW of the controls. This was gradually decreased in the 24-h ADR kidneys and further decreased in the 10-day ADR, indicating a gradual decrease in glomerular sialic acid content.(ABSTRACT TRUNCATED AT 250 WORDS)
Skutelsky
E
E
Department of Pathology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Hartzan
S
S
Socher
R
R
Gafter
U
U
D000818:Animals; D000838:Anions / Q000378:metabolism*; D001485:Basement Membrane / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D004317:Doxorubicin; D006046:Gold / Q000378:metabolism; D006651:Histocytochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000378:metabolism*; D037102:Lectins; D008297:Male; D008854:Microscopy, Electron; D009401:Nephrosis / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D011107:Polylysine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000838:Anions; D037102:Lectins; C089532:cationic colloidal gold; D011107:Polylysine; D006046:Gold; D004317:Doxorubicin