Altered antioxidant defence in a mouse adriamycin model of glomerulosclerosis.
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.
Deman
A
A
Department of Human Anatomy, Vrije Universiteit Brussel and Academic Hospital of the Vrije Universiteit Brussel, Brussels, Belgium.
Ceyssens
B
B
Pauwels
M
M
Zhang
J
J
Houte
K V
KV
Verbeelen
D
D
Van den Branden
C
C
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
D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase