title: Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride-induced hepatic injury in the Hanover Wistar rat.
abstract: Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD-1) is increased in the urine of rats with carbon tetrachloride (CCl(4))-induced hepatotoxicity. The present experiments aimed to investigate further the usefulness of urinary SOD-1 as a non-invasive biomarker of liver injury. Two investigations were carried out, a dose response study and a time course study. In the dose response study, rats were given a single dose of CCl(4) at 0 (control), 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 and 0.80 ml/kg and urine samples collected from 12 to 36 h postdosing. In the time course study, rats were dosed at 0.80 ml/kg CCl(4) and urine sampled at 4, 12, 24 and 36 h postdosing. In both studies, the presence of SOD-1 in the urine was confirmed by Western blotting with an SOD-1 antibody. In the dose response study, serum SOD activity was elevated in all CCl(4)-treated animals and urinary SOD-1 activity was increased 2.2 times at the lowest dose (0.10 ml/kg) and 60.4 times at the highest CCl(4) dose level (0.80 ml/kg). In the time course study, urinary SOD-1 was first detected in samples collected from 4 to 12 h postdosing. We conclude that urinary SOD-1 has potential as a sensitive non-invasive biomarker of CCl(4)-induced hepatocellular injury.
authors.affiliation: Department of Pharmaceutical and Biological Chemistry, University of London, UK. rosemary.smyth@pharmacy.ac.uk
authors.forename: Rosemary
authors.initials: R
authors.lastname: Smyth
authors.forename: Michael R
authors.initials: MR
authors.lastname: Munday
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: York
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Clarke
authors.forename: Theo
authors.initials: T
authors.lastname: Dare
authors.forename: John A
authors.initials: JA
authors.lastname: Turton
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015153:Blotting, Western / Q000379:methods; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000473:pathology; D004796:Clinical Enzyme Tests / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000652:urine*
chemical_list: D015415:Biomarkers; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase