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Human & Experimental Toxicology
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{alpha}-glutathione s-transferase ({alpha}-GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat

H. Clarke

Department of Pharmacology, University College Dublin, Fosters Avenue, Blackrock, Dublin 4, Ireland

DA Egan

Department of Pharmacology, University College Dublin, Fosters Avenue, Blackrock, Dublin 4, Ireland

M. Heffernan

BIOTRIN International, 93 The Rise Mount Merrion, Co. Dublin, Ireland

S. Doyle

BIOTRIN International, 93 The Rise Mount Merrion, Co. Dublin, Ireland

C. Byrne

BIOTRIN International, 93 The Rise Mount Merrion, Co. Dublin, Ireland

C. Kilty

BIOTRIN International, 93 The Rise Mount Merrion, Co. Dublin, Ireland

MP Ryan

Department of Pharmacology, University College Dublin, Fosters Avenue, Blackrock, Dublin 4, Ireland

1 The use of the cytoplasmic enzyme, alpha glutathione s-transferase ({alpha}-GST) as an early index of carbon tetrachloride (CCl4) toxicity in the rat was investigated and compared with a standard enzyme marker, aspartate aminotransferase (AST). The hepatotoxic effects of CCl 4 in the rat were determined in a time and dose-response study.

2 Following CCl 4 exposure, {alpha}-GST release was shown to be an earlier and more sensitive biomarker of hepatotoxicity than AST.

3 Significant increases in {alpha}-GST were detected 2 h after CCl4 exposure. Using the enzyme marker AST, this early hepatotoxic injury went undetected. At 6 and 16 h, {alpha}-GST was also a more sensitive indicator of hepatotoxicity than AST.

4 {alpha}-GST release was significantly increased at a dose of 5 µl/kg, the lowest concentration of CCl4 administered and clearly responded in a dose-dependent manner with increasing doses of CCl4. In contrast, release of AST did not reach statistical significance until a dose of 25 µl/kg.

5 Thus, these findings indicate that {alpha}-GST is a more sensitive and more accurate reflector of CCl4 induced hepatotoxicity than AST.

Key Words: {alpha} glutathione s-transferase • {alpha}-GST • aspartate amino transferase • AST • hepatotoxicity • carbon tetrachloride • biomarker

Human & Experimental Toxicology, Vol. 16, No. 3, 154-157 (1997)
DOI: 10.1177/096032719701600304


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