title: Mechanisms of iron-induced proximal tubule injury in rat remnant kidney.
abstract: The proposition that proximal tubule (PT) iron accumulation may cause PT injury by lysosomal destabilization or reactive oxygen species generation in human and animal chronic renal disease was examined in partially nephrectomized [remnant kidney (RK)] and sham-operated (SO) Wistar rats. Electron microscopic histochemistry with horseradish peroxidase indicated iron uptake into and release from lysosomes. PT cytoplasmic iron was seen in RK but not in SO by energy-dispersive X-ray spectrometry. Total (9.66 +/- 1.89 vs. 3.30 +/- 0.31 nmol/mg protein; P < 0.01), low-molecular-weight (1.39 +/- 0.09 vs. 0.91 +/- 0.07; P < 0.001), and catalytic iron (1.88 +/- 0.27 vs. 1.28 +/- 0.09; P = 0.05) were higher in RK cytoplasm than in SO. Lysosomal enzyme activity was greater in RK than in SO [e.g., N-acetyl-beta-D-glucosaminidase (NAG): 0.75 +/- 0.05 vs. 0.57 +/- 0.06 mumol p-nitrophenol.h-1.mg protein-1; P < 0.05] and was increased further by chronic iron loading (e.g., RK and NAG: 0.84 +/- 0.04 vs. 0.60 +/- 0.07; P < 0.05). There was no enzymatic evidence of lysosomal fragility, and chronic iron loading of RK decreased fragility as assessed by NAG release (1.36 +/- 0.14 vs. 2.17 +/- 0.14; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University of Sydney, Westmead Hospital, New South Wales, Australia.
authors.forename: D C
authors.initials: DC
authors.lastname: Harris
authors.forename: Y C
authors.initials: YC
authors.lastname: Tay
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: B J
authors.initials: BJ
authors.lastname: Nankivell
mesh_terms: D000818:Animals; D006651:Histocytochemistry; D007501:Iron / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009392:Nephrectomy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D007501:Iron