REACTIVE OXYGEN SPECIES AND ANTIOXIDANT DEFENSE IN PUROMYCIN AMINONUCLEOSIDE GLOMERULOPATHY

Results from several radical scavenger studies indirectly suggested an involvement of reactive oxygen species in the pathogenesis of puromyc in aminonucleoside glomerulopathy. In this study, generation of reacti ve oxygen species was examined directly in glomeruli isolated from rat s in the acute phase of puromycin aminonucleoside nephrosis and relate d to the changes in the glomerular antioxidant defense. Five and nine days after puromycin aminonucleoside injection, gross proteinuria, red uced creatinine clearances, and typical changes of glomerular morpholo gy were present. Levels of reactive oxygen species were increased eigh tfold in glomeruli isolated 15 min after puromycin aminonucleoside inj ection, returned to baseline levels on days 1 and 5 after injection, a nd rose again to 14-fold on day 9 after injection, as determined by ch emiluminescence with luminol. Further analysis of increased glomerular radical generation, using the chemiluminescence enhancer lucigenin an d different radical scavengers, suggested a predominant involvement of hydroxyl radical and hydrogen peroxide in the initial increase in rea ctive oxygen species 15 min after puromycin aminonucleoside. Nine days after induction of nephrosis, primarily superoxide anion and hydroxyl radical were found to contribute to increased reactive oxygen species . Despite oxidative stress, antioxidant enzymes were not induced in th e course of nephrosis. On the contrary, catalase and glutathione perox idase activities declined 9 d after puromycin aminonucleoside injectio n. The results indicate that a transient increase in glomerular reacti ve oxygen species is sufficient to induce the oxidative glomerular inj ury observed in this model and that the glomerulus may not necessarily respond to oxidative stress with an induction of antioxidant enzymes.