Nephrol Dial Transplant (2001) 16: 147-150
© 2001 European Renal Association-European Dialysis and Transplant Association
Brief Reports
Altered antioxidant defence in a mouse adriamycin model of glomerulosclerosis
1 Department of Human Anatomy, 2 Division of Pathology and 3 Department of Nephrology, Vrije Universiteit Brussel and Academic Hospital of the Vrije Universiteit Brussel, Brussels, Belgium
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 µmol/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.
Conclusion. The fast development of glomerulosclerosis combined with an altered antioxidant status makes this mouse adriamycin model a suitable alternative for the slower rat models.
Keywords: adriamycin; antioxidant enzymes; chronic renal failure; glomerulosclerosis; oxidative stress
Correspondence and offprint requests to: Dr Christiane Van den Branden, Human Anatomy, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
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