title: Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis.
abstract: We studied the possibility that tubule fluid iron could be involved in the pathogenesis of the tubulo-interstitial injury associated with primary glomerular disease. Tubule fluid iron is determined by the magnitude of the glomerular leak for transferrin and the iron saturation of transferrin. To minimize tubule fluid iron in an experimental model of glomerulonephritis, iron deficiency was induced in rats prior to the induction of nephrotoxic serum nephritis. Iron deficiency did not effect the development of glomerular disease as determined by proteinuria, but had a marked effect on preventing the development of tubulo-interstitial disease and renal functional deterioration. There was also a strong correlation between the amount of functional deterioration and extent of tubulo-interstitial disease and urinary iron excretion in both the control and iron deficient animals. It is proposed that injury results from iron being dissociated from transferrin at the more acid pH of the tubule fluid. Iron, a transition element, is able to catalyze the Haber-Weiss reaction with the formation of free hydroxyl radicals which causes renal tubule cell injury. This tubulo-interstitial injury is the major determinate of progressive renal functional deterioration in this experimental model of glomerulonephritis.
authors.affiliation: Department of Medicine and Pathology, Veterans Administration Medical Center, Denver, Colorado.
authors.forename: A C
authors.initials: AC
authors.lastname: Alfrey
authors.forename: D H
authors.initials: DH
authors.lastname: Froment
authors.forename: W S
authors.initials: WS
authors.lastname: Hammond
mesh_terms: D000818:Animals; D005609:Free Radicals; D007501:Iron / Q000009:adverse effects*; D000090463:Iron Deficiencies; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009395:Nephritis, Interstitial / Q000209:etiology*; D011507:Proteinuria / Q000150:complications; D051381:Rats; D011919:Rats, Inbred Strains; D014168:Transferrin / Q000378:metabolism
chemical_list: D005609:Free Radicals; D014168:Transferrin; D007501:Iron