Evidence for the role of oxygen radicals in acute nephrotoxic nephritis.
Acute glomerular injury in the rat has been induced by the intrarenal, intraarterial infusion of sheep antibody to glomerular basement membrane (antiglomerular basement membrane). The antiglomerular basement membrane antibody has been verified to be of the variety that is complement and neutrophil dependent for the induction of acute proteinuria, which peaks during the first 24 hours. Following injection of the antibody, acute, intense, glomerular injury resulted, with the denuding of glomerular vascular basement membrane associated with extensive damage or destruction of glomerular endothelial cells and fusion of epithelial cell foot processes. Treatment of animals with catalase produced, in a dose-dependent manner, as much as 75% protection against glomerular injury, as assessed by reduction in the proteinuria. Treatment of animals with superoxide dismutase caused a small reduction in the degree of glomerular injury, again assessed by a reduction in proteinuria. However, this protective effect of superoxide dismutase was not found to be statistically significant. The hydroxyl radical scavenger, dimethyl sulfoxide, which has been shown to protect against endothelial cell injury following systemic activation of complement, was not protective in the anti-GBM model. Morphologically, glomeruli from catalase-protected rats showed numerous neutrophils but little or no evidence of injury of either glomerular endothelial or epithelial cells. These data suggest that acute glomerular injury produced by antiglomerular basement membrane is related to H2O2 production from activated neutrophils.
D000208:Acute Disease; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D002374:Catalase / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D009393:Nephritis / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*
D006878:Hydroxides; D013481:Superoxides; D017665:Hydroxyl Radical; D003165:Complement System Proteins; D006861:Hydrogen Peroxide; D002374:Catalase; D004121:Dimethyl Sulfoxide