Role of xanthine oxidase in passive Heymann nephritis in rats

Passive Heymann nephritis (PHN) in rats is a model of human membranous neph ropathy characterized by formation of subepithelial immune deposits in the glomerular capillary wall and complement activation. Oxygen radicals have b een implicated in the subsequent glomerular damage which leads to proteinur ia. This study examines the involvement of xanthine oxidase in this process . Xanthine oxidase activity was increased nearly twofold in glomeruli isola ted 1 and 12 d after induction of PHN, and this was associated with increas ed glomerular superoxide anion generation. Analysis of glomerular samples b y Northern and Western blotting revealed no quantitative changes in xanthin e oxidoreductase expression in PHN, suggesting conversion of xanthine dehyd rogenase to the oxidase form as the cause of increased activity. Treatment of mts with tungsten, an inhibitor of xanthine oxidase, before induction of BHN resulted in a marked decrease in glomerular xanthine oxidase activity and superoxide anion generation, and decreased proteinturia by 80% (day 12: 423 +/- 245 mg/d in PHN versus 78 +/- 53 mg/d in tungsten-treated PHN anim als, P < 0.01), These findings point to a pivotal role of xanthine oxidase in the pathophysiology of PHN and could be of importance in the therapy of human membranous nephropathy.