ANTIOXIDANTS PROTECT PODOCYTE FOOT PROCESSES IN PUROMYCIN AMINONUCLEOSIDE-TREATED RATS

Whether a reduction in urinary protein excretion in rats coadministere d puromycin aminonucleoside and antioxidants was associated with a red uction in alterations to glomerular epithelial cell (podocyte) ultrast ructure was examined. Daily urinary protein excretion was measured in rats that received a single iv injection of saline or puromycin aminon ucleoside with or without coadministration of antioxidants. The coadmi nistration of alpha-tocopherol/ascorbic acid, dimethyl thiourea, or su peroxide dismutase to puromycin aminonucleoside-treated rats reduced p roteinuria by approximately 90, 40, and 60%, respectively, over the 18 -day period studied. For a second group of rats, daily urinary protein excretion was measured and kidneys were processed for light microscop y and transmission and scanning electron microscopy 4, 5, and 10 days after injection. Transmission electron microscopic morphometric analys is of glomeruli from puromycin aminonucleoside-treated rats coadminist ered antioxidants revealed significantly reduced foot process effaceme nt on Days, 4, 5, and 10 compared with rats that received puromycin am inonucleoside alone. Thus, at Day 10, puromycin aminonucleoside-treate d rats coadministered alpha-tocopherol/ascorbic acid, dimethyl thioure a, or superoxide dismutase contained 90, 74, and 88% (P < 0.01 in all cases) more glomerular epithelial cell filtration slits per unit lengt h of glomerular basement membrane than rats treated with puromycin ami nonucleoside alone. In contrast, by scanning electron microscopy, the antioxidants were found to provide no protection against the changes o ccurring in glomerular epithelial cell bodies and major processes. The se results provide further evidence of a role for reactive oxygen spec ies in puromycin aminonucleoside nephrosis and indicate that the antio xidants provide protection against the changes occurring in glomerular epithelial cell foot processes.