Low molecular weight heparin in the treatment of puromycin-induced nephrosis.
Heparin may have a beneficial effect in proteinuric renal diseases, where negative charges of the glomerular capillary membrane are compromised. We evaluated the role of low molecular weight heparin (LMWH - 3000 Da) in puromycin aminonucleoside (PAN)-induced focal and segmental glomerulosclerosis in male Wistar rats: Controls (C) n=7, LMWH-treated group, n=9, subcutaneously (SC), 6 mg/kg every day. The PAN group (n=7) received 7 doses on weeks 0, 1, 2, 4, 6, 8, 10 (SC - 2mg/100g), and a group PAN+LMWH (n=6). After 12 weeks, cholesterol and triglycerides were higher in nephrotic groups, as well as proteinuria and urinary IgG. Kidney weight, glomerular volume, and glomerular sclerosis index were higher in the PAN-treated groups. Glomerular capillary length density (L(Vcap)) and glomerular capillary surface density (S(Vcap)) were lower in the PAN group, and mesangial fractional volume was higher. Fibronectin immunostaining was more intense in the PAN group, and collagens I and III were absent in the studied glomeruli. Thus, LMWH prevented mesangial expansion and capillaries changes, showing antiproliferative properties, despite worsening glomerular permeability changes in the PAN model. In conclusion, LMWH interferes in the complications of PAN model, but not through inhibition of the proteinuria.
Nephrology Division, University of State of Rio de Janeiro, Rio de Janeiro, Brazil.
Ana Maria Ribeiro
AM
Dos Santos
Albanita Viana
AV
de Olveira
Carla Cavalheiro
CC
da Silva Lemos
Carlos Alberto
CA
Mandarim-de-Lacerda
Rachel
R
Bregman
D000818:Animals; D004353:Drug Evaluation, Preclinical; D005353:Fibronectins / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000188:drug therapy*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D011507:Proteinuria / Q000188:drug therapy; D011692:Puromycin Aminonucleoside; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D006495:Heparin, Low-Molecular-Weight; D011692:Puromycin Aminonucleoside