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Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride‐induced hepatic injury in the Hanover Wistar rat
Author(s) -
Smyth Rosemary,
Munday Michael R.,
York Malcolm J.,
Clarke Christopher J.,
Dare Theo,
Turton John A.
Publication year - 2009
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2009.00666.x
Subject(s) - carbon tetrachloride , urine , superoxide dismutase , urinary system , biomarker , medicine , chemistry , pharmacology , oxidative stress , biochemistry , organic chemistry
Summary 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.