title: Altered antioxidant defence in a mouse adriamycin model of glomerulosclerosis.
abstract: BACKGROUND
  Antioxidant enzyme status changes in experimental models of chronic renal disease with glomerulosclerosis. Most of the studies are performed in rats. We now investigate whether a mouse model with more rapid development of glomerulosclerosis is suitable for the study of radical-associated renal disease.
  
  
  METHODS
  Female BALB/c mice are injected intravenously with a single dose of adriamycin (10 mg/kg). The development of glomerular and interstitial injury is evaluated by means of renal function parameters and histology. Renal cortex activities of catalase, Cu/Zn and Mn superoxide dismutase and glutathione peroxidase are measured by enzymatic techniques, and their mRNA levels by Northern blot analysis.
  
  
  RESULTS
  The mice develop proteinuria and hypercholesterolaemia; glomerulosclerosis is present 20 days after adriamycin injection. Involvement of reactive oxygen intermediates in the disease process is supported by an increased cortex level of glutathione (1.77+/-0.13 vs 1.31+/-0.12 micromol/g kidney; P = 0.021) and ferric iron deposition in the tubulointerstitial compartment. Glomerulosclerosis and tubulointerstitial lesions are accompanied by decreased cortex activities of catalase (0.19+/-0.01 vs 0.23+/-0.01 U/mg protein; P = 0.024), glutathione peroxidase (0.28+/-0.01 vs 0.32+/-0.01 U/mg protein; P = 0.049) and Mn superoxide dismutase (6.61+/-0.91 vs 9.25+/-0.99 U/mg protein, P = 0.020). We find decreased cortex mRNA levels only for glutathione peroxidase.
  
  
  CONCLUSIONS
  The fast development of glomerulosclerosis combined with an altered antioxidant status makes this mouse adriamycin model a suitable alternative for the slower rat models.
authors.affiliation: Department of Human Anatomy, Vrije Universiteit Brussel and Academic Hospital of the Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Deman
authors.forename: B
authors.initials: B
authors.lastname: Ceyssens
authors.forename: M
authors.initials: M
authors.lastname: Pauwels
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: K V
authors.initials: KV
authors.lastname: Houte
authors.forename: D
authors.initials: D
authors.lastname: Verbeelen
authors.forename: C
authors.initials: C
authors.lastname: Van den Branden
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase