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Identification of superoxide dismutase as a potential urinary marker of carbon tetrachloride-induced hepatic toxicity.

Smyth, R; Turton, JA; Clarke, CJ; York, MJ; Dare, TO; Lane, CS; Munday, MR; (2008) Identification of superoxide dismutase as a potential urinary marker of carbon tetrachloride-induced hepatic toxicity. Food Chem Toxicol , 46 (9) 2972 - 2983. 10.1016/j.fct.2008.05.041.

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Abstract

The aim of this study was the identification of a novel protein marker of hepatotoxicity in rat urine. Rats were dosed by gavage with carbon tetrachloride (CCl(4)) to induce acute liver injury. Surface enhanced laser desorption/ionisation (SELDI) ProteinChip technology revealed the appearance of a 15.7 kDa protein in the CCl(4)-treated rat urine. One-dimensional sodium dodecyl sulphate polyacrylamide electrophoresis (SDS-PAGE) identified an 18.4 kDa protein in the CCl(4)-treated rat urine. The appearance of either protein was coincident over a time course during which they first appeared at 12h post-dosing, peaked at 36h and had disappeared again within 3 days post-dosing. The protein was identified by in-gel digestion and nano-electrospray (nano-ES)-tandem mass spectrometry as Cu/Zn superoxide dismutase (SOD-1). SOD activity was found to be increased by 61.4-fold in CCl(4)-treated rat urine. Western blots of tissue homogenates from the rats revealed a time-dependent loss of SOD-1 from the livers of CCl(4)-treated rats matching the time course of SOD-1 appearance in urine. SOD-1 is not specifically located in liver; however, its appearance in urine in response to acute CCl(4)-induced hepatotoxicity is a novel finding; this coupled with loss from the liver following injury suggests urinary SOD-1 may be a potential marker of hepatotoxicity.

Type:Article
Title:Identification of superoxide dismutase as a potential urinary marker of carbon tetrachloride-induced hepatic toxicity.
Location:England
DOI:10.1016/j.fct.2008.05.041
Language:English
Keywords:Amino Acid Sequence, Animals, Biological Markers, Blotting, Western, Carbon Tetrachloride Poisoning, Dose-Response Relationship, Drug, Drug-Induced Liver Injury, Electrophoresis, Polyacrylamide Gel, Female, Kidney, Liver, Liver Function Tests, Molecular Sequence Data, Organ Size, Proteinuria, Rats, Rats, Wistar, Superoxide Dismutase, Tandem Mass Spectrometry
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutical and Biological Chemistry
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Research Department of General Surgery

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