Preclinical Hepatotoxicity

Summary
  • αGST rises earlier than transaminases.
  • αGST falls faster than other biomarkers after the injury is removed.
  • αGST provides better toxicokinetics.
  • αGST increases are statistically more significant.
  • αGST levels are unaffected by haemolysis.
  • αGST is a more specific indicator of liver injury.
  • Low αGST levels almost exclude acute liver injury.
  • Assays can be used in rat, mouse and primate samples. 

 

Selected Articles

 

Rodent Hepatotoxicity
 

1) Antioxidant and hepatoprotective actions of medicinal herb, Terminalia catappa L. from Okinawa Island and its tannin corilagin.

Kinoshita, S., Inoue, Y., Nakama, S., Ichiba, T. and Aniya, Y. (2007). Phytomedicine. 14(11) 755-62.

  • αGST could demonstrate decreases in toxicity.

 


2) Valproic Acid I: Time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats.

Tong, V., Teng, X.W., Chang, T.K., and Abbott, F.S. (2005). Toxicological Sciences 86(2) 427–435.

  • αGST was a more specific and robust biomarker of hepatotoxicity.
  • Valproic acid induces haemolysis which makes transaminases unreliable biomarkers.
  • αGST was unaffected and was a sensitive biomarker of hepatotoxicity.

 


3) Alpha-glutathione S-transferase in the assessment of hepatotoxicity--its diagnostic utility in comparison with other recognized markers in the Wistar Han rat.

Giffen, P.S., Pick, C.R., Price, M.A., Williams, A. and York, M.J. (2002). Toxicol. Pathol. 30(3) 365-72.

  • αGST was a more liver specific than other biomarkers.
  • αGST was more stable on freeze-thawing.

 

4) Attenuation of hepatic fibrosis observed with a “gutless” adenoviral vector.

King L.M. et al. (2002). Poster presented at the 40th meeting of the Society of Toxicology. March 19-21 2002, Nashville, USA.

  • Serum αGST was a more sensitive indicator of liver effects than transaminases.

 


5) Glutathione S-Transferase (GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat.

Clarke, H., Egan, D.A., Heffernan, M., Doyle, S., Byrne, C., Kilty, C. and Ryan, M.P. (1997). Human and Experimental Toxicology 16 154-157.

  • αGST release was closely related to the dose of toxin.
  • αGST rose in advance of AST.
  • αGST showed the toxicokinetics more clearly.
  • αGST elevations were statistically more significant.

 

Primate Hepatotoxicity

  • αGST rose faster and to a greater extent than a range of traditional biomarkers in experimental models of primate hepatotoxicity.
  • The Argutus Medical HEPKIT Alpha GST EIA can be used to measure αGST in primate serum.

 

1) Alpha glutathione S-transferase as biomarker for liver injury in Cynomolgus monkeys – validation of a human assay.
Muller, W. et al. (2001).  Poster presented at the Society of Toxicology meeting. San Francisco, March 25-29, 2001.
 
2) Improved detection of acute drug-induced liver toxicity by measurement of serum alpha glutathione S-transferase in Cynomolgus monkeys.
Mohr, S. et al. (2002). Poster presented at the Society of Toxicology meeting. March 19-21 2002, Nashville, USA.
 


 

 

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