Effect of hepatotoxic doses of paracetamol and carbon tetrachloride on the serum and hepatic carboxylesterase activity in mice.
The carboxylesterase activity in the serum and liver of untreated Swiss-Webster mice, and in mice administered hepatotoxic doses of either CCl4 or paracetamol was studied. In addition to p-nitrophenyl acetate (p-NpAc) and diethylsuccinate, a sensitive, spectrophotometric substrate, methyl beta-(1-pentylthio) propiothioate was used to determine the esterase activity. At 24 h after treatment with CCl4 (1 mL kg-1), the liver esterase activity in the soluble fraction acting on p-NpAc was increased 1.7-fold whereas the microsomal esterase activity decreased by one-half. The serum esterase activity increased 2.4- to 3.4-fold depending upon the substrate used. Esterase activity assays of sliced gels from isoelectric focusing (IEF) of serum from mice treated with CCl4 indicated the presence of at least three additional esterase peaks when compared with serum of control mice. These peaks correlated with esterase bands visualized after staining the IEF gel with 1-naphthyl acetate. Furthermore, these esterase bands matched closely the esterase bands from microsomes of normal mice. The serum esterase activity was analysed at 4, 8, 12 and 24 h after paracetamol (400 mg kg-1) treatment. Serum esterase activity remained unchanged or decreased marginally depending on the treatment time and substrate used. Serum glutamic oxalacetic transaminase levels in CCl4- and paracetamol-treated mice, however, were significantly elevated compared with control mice. These results suggest that acute liver damage might cause the release of carboxylesterase activity to the soluble intracellular and extracellular compartments, including blood serum, with some but not all toxicants. The results also indicate that the different modes of action of the two chemicals may account for the difference in the serum carboxylesterase activity of the experimental animals.
Huang
T L
TL
Department of Entomology, University of California, Davis 95616.
Villalobos
S A
SA
Hammock
B D
BD
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002265:Carboxylic Ester Hydrolases / Q000097:blood* / Q000187:drug effects / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008107:Liver Diseases / Q000201:enzymology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology; D051379:Mice
D015415:Biomarkers; D000082:Acetaminophen; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D002265:Carboxylic Ester Hydrolases