CYTOTOXICITY OF SERA FROM RATS WITH PUROMYCIN AMINONUCLEOSIDE NEPHROSIS

Administration of puromycin aminonucleoside (PAN) to rats induces acut e nephrosis with hyperlipidemia, and, in some experimental conditions, it results in chronic focal glomerulosclerosis, In this study, we exa mined the cytotoxicity of serum ii om rats with PAN-induced nephrosis, since hypercholesterolemia is considered to cause injury to vascular walls in atherosclerosis, the mechanism of which is analogous to that of glomerulosclerosis. About half of the tested sera from nephrotic ra ts (9 out of 17) were cytotoxic to cultured aortic endothelial cells, The toxic substance(s) was heat-stable and was extracted in the lipid Fraction. Serum levels of triglyceride and cholesterol were markedly h igher in the group of rats with cytotoxic serum than in the group with noncytotoxic serum, No cytotoxicity was associated with sera from con trol rats or the corresponding lipid fractions, Cytotoxic sera were al so effective against cultured glomerular epithelial and mesangial cell s, These results indicate that cytotoxic lipid is produced in rats wit h PAN nephrosis and the results raise tile possibility that the cytoto xic lipid in nephrotic serum might contribute to lipid-mediated glomer ular injury which may induce glomerulosclerosis at a subsequent stage.