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Comprehensive characterization of serum clinical chemistry parameters and the identification of urinary superoxide dismutase in a carbon tetrachloride-induced model of hepatic fibrosis in the female Hanover Wistar rat
- Source :
- International journal of experimental pathology. 88(5)
- Publication Year :
- 2007
-
Abstract
- Carbon tetrachloride (CCl(4)) was used to induce liver fibrosis in the rat. Using this model, we have identified changes in serum and urinary clinical chemistry parameters, and characterized histopathological lesions in the liver. Two experiments were conducted. In Experiment 1, rats were dosed at six levels of CCl(4) (0.06-0.36 ml/kg) twice weekly for 6 weeks, followed by a 6-week non-dosing recovery period (week 12). Livers were removed for histology at 6 and 12 weeks and serum parameters analysed. In Experiment 2, rats were given seven dose levels of CCl(4) (0.4-1.0 ml/kg) twice weekly for 6 weeks, followed by a 6-week recovery period (week 12); urine samples were analysed at 3, 6, 9 and 12 weeks using one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Liver fibrosis was evident at 6 weeks in Experiments 1 and 2, and the activity of serum enzymes (including alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase) was increased. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis (Experiment 2) revealed a protein band at 18.4 kDa in urine from rats treated with CCl(4), not present in control urine, which was identified as copper/zinc superoxide dismutase (Cu/Zn SOD). Western blotting revealed that SOD was increased in urine from rats treated with CCl(4) at 3 and 6 weeks, but not at 9 and 12 weeks. We conclude that Cu/Zn SOD is a urinary marker of hepatic necrosis, but not hepatic fibrosis.
- Subjects :
- Time Factors
Superoxide Dismutase
Alanine Transaminase
Original Articles
Fibrosis
Rats
Necrosis
Glutamate Dehydrogenase
Liver
Models, Animal
Animals
Electrophoresis, Polyacrylamide Gel
Female
Aspartate Aminotransferases
Chemical and Drug Induced Liver Injury
Rats, Wistar
Carbon Tetrachloride
Biomarkers
Transaminases
Subjects
Details
- ISSN :
- 09599673
- Volume :
- 88
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- International journal of experimental pathology
- Accession number :
- edsair.pmid..........1e950bdb752a3330dab3ce97a9da96e4