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 allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and urinary protein excretion were examined in puromycin aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced proteinuria by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared 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 activity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten to puromycin aminonucleoside-treated rats did not reduce proteinuria or alter the number of filtration slits. Rats co-administered tungsten and puromycin aminonucleoside had significantly reduced renal xanthine oxidase and combined 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 allopurinol in puromycin aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.