PODOCYTE ARCHITECTURE IN PUROMYCIN AMINONUCLEOSIDE-TREATED RATS ADMINISTERED TUNGSTEN OR ALLOPURINOL

The role of xanthine oxidase as a source of reactive oxygen species in puromycin aminonucleoside nephrosis was examined. The effects of allo purinol (a xanthine oxidase inhibitor as well as a reactive oxygen spe cies scavenging enzyme) and tungsten (a specific xanthine oxidase inhi bitor) on glomerular epithelial cell ultrastructure, renal xanthine ox idase and xanthine dehydrogenase activity, and urinary protein excreti on were examined in puromycin aminonucleoside-treated rats. Go-adminis tration of allopurinol to such rats reduced proteinuria by approximate ly 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compare d to rats that received puromycin aminonucleoside alone. Unexpectedly, co-administration of allopurinol to puromycin aminonucleoside-treated rats did not reduce xanthine oxidase activity; however,the combined a ctivity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Go-administration of tungsten to puromycin amin onucleoside-treated rats did not reduce proteinuria or alter the numbe r of filtration slits. Rats co-administered tungsten and puromycin ami nonucleoside had significantly reduced renal xanthine oxidase and comb ined xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared to rats treated with puromycin aminonucleoside alone. These results provide evidence that the protection provided by allopu rinol in puromycin aminonucleoside-treated rats is due to the antioxid ant properties of allopurinol, rather than to its activities as a xant hine oxidase inhibitor.