Experimental nephrotic syndrome in the rat induced by puromycin aminonucleoside. Plasma and urinary lipoproteins

Nephrotic syndrome (ascites, proteinuria, hypoalbuminemia, and hyperlipidemia) was induced in male Wistar rats by daily administration of puromycin aminonucleoside (20 mg/Kg). Hyperlipidemia was the result of a marked increase of all plasma lipids particularly triacylglycerols (7 to 8-fold the values found in the pair fed control rats). All plasma lipoprotein fractions were increased in nephrotic rats. VLDL increased 14-fold; LDL and HDL were 7- and 6.5-fold respectively above the pairfed control values. The apoprotein pattern of nephrotic VLDL was characterized by a loss of apoC-1 peptide and the presence of two bands in the region of ARP and apoA-1 peptides. SDS polyacrylamide gel electrophoresis indicated an increased content of ARP in nephrotic VLDL. Nephrotic LDL but not control LDL contained peptides entering the running gel in 8 M-urea gels in the region of ARP, A-1 and C peptides. Nephrotic HDL were almost devoided of ARP and apoA-IV peptides whereas control HDL contained significant amounts of these peptides. The urine of nephrotic rats contained a large amount of lipids (21.9 vs 1.5 M × 10^?6/day). Fatty acids, cholesteryl esters, and phospholipids were the major lipids of nephrotic urine. More than 72% of these lipids were isolated by preparative ultracentrifugation into three fractions: Total Low Density Lipoproteins (< 1.050 g/ml), High Density Lipoproteins (1.063 to 1.210 g/ml) and Ultracentrifugal Residue (> 1.210 g/ml) which contained respectively 7.4, 44.4, and 48.2% of the total recovered lipids. Urinary excretion of HDL was much greater than that of TLDL indicating that lipoproteinuria of aminonucleoside induced nephrotic syndrome was selective. The relationship between these findings, previously reported data and the alterations of plasma and urinary lipoproteins in human nephrotic syndrome is discussed.