Alpha-glutathione s-transferase (alpha-GST) release, an early indicator of carbon tetrachloride hepatotoxicity in the rat.
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 CCl4 in the rat were determined in a time and dose-response study. 2. Following CCl4 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 microliters/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 microliters/kg. 5. Thus, these findings indicate that alpha-GST is a more sensitive and more accurate reflector of CCl4 induced hepatotoxicity than AST.
Clarke
H
H
Department of Pharmacology, University College Dublin, Ireland.
Egan
D A
DA
Heffernan
M
M
Doyle
S
S
Byrne
C
C
Kilty
C
C
Ryan
M P
MP
D000284:Administration, Oral; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000097:blood*; D007124:Immunoenzyme Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D002251:Carbon Tetrachloride; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases