Lovastatin ameliorates depressed intraglomerular proteolytic activities in experimental nephrotic syndrome.
Lipid abnormalities have been implicated in the pathogenesis of glomerulosclerosis in experimental models of kidney disease. In previous studies it has been shown that Adriamycin-induced nephropathy is associated with reduced activities of glomerular proteinases. This observation led to the hypothesis that reduced proteolytic activities may be responsible for mesangial protein accumulation, which ultimately leads to global sclerosis of the glomerular tuft. The aim of the present study was to investigate whether lovastatin treatment, which prevents progressive glomerulosclerosis in experimental nephrotic syndrome, would also have an effect on glomerular proteinase activities. Adriamycin administration resulted in a persistent nephrotic syndrome with gross proteinuria (377 +/- 26 mg/24 h), hypoalbuminemia (2.1 +/- 0.12 vs. 2.8 +/- 0.02 g/dl), hypercholesterolemia (575 +/- 74 vs. 68 +/- 1.5 mg/dl) and elevated triglyceride levels (1,155 +/- 78 vs. 57 +/- 8 mg/dl). Glomerular azocaseinolytic activities both at pH 5.4 (-21%) and 7.4 (-37%) were significantly reduced. In contrast to human subjects, nephrotic rats that were treated with lovastatin displayed reduced triglyceride levels (767 +/- 134 mg/dl); their serum cholesterol, however, remained unchanged. In terms of glomerular proteolytic enzyme activities, the decline in azocaseinolysis at both pH values was, at least partly, prevented by lovastatin. On the basis of these data, it appears that the beneficial effect of lovastatin on the evolution of glomerulosclerosis in the nephrotic rat is associated with the conservation of glomerular proteolytic activities.
Teschner
M
M
Division of Nephrology, University of Würzburg, Germany.
Paczek
L
L
Schaefer
L
L
Bahner
U
U
Heidland
A
A
Schaefer
R M
RM
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D004317:Doxorubicin; D010450:Endopeptidases / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000201:enzymology / Q000517:prevention & control; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology*; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew
D004317:Doxorubicin; D008148:Lovastatin; D010450:Endopeptidases