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 Swis s-Webster mice, and in mice administered hepatotoxic doses of either C Cl4 or paracetamol was studied. In addition to p-nitrophenyl acetate ( p-NpAc) and diethylsuccinate, a sensitive, spectrophotometric substrat e, 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 i ncreased 1.7-fold whereas the microsomal esterase activity decreased b y one-half. The serum esterase activity increased 2.4- to 3.4-fold dep ending upon the substrate used. Esterase activity assays of sliced gel s from isoelectric focusing (IEF) of serum from mice treated with CCl4 indicated the presence of at least three additional esterase peaks wh en compared with serum of control mice. These peaks correlated with es terase bands visualized after staining the IEF gel with 1-naphthyl ace tate. Furthermore. these esterase bands matched closely the esterase b ands from microsomes of normal mice. The serum esterase activity was a nalysed at 4, 8, 12 and 24 h after paracetamol (400 mg kg-1) treatment . Serum esterase activity remained unchanged or decreased marginally d epending on the treatment time and substrate used. Serum glutamic oxal acetic transaminase levels in CCl4- and paracetamol-treated mice. howe ver, were significantly elevated compared with control mice. These res ults suggest that acute liver damage might cause the release of carbox ylesterase activity to the soluble intracellular and extracellular com partments, including blood serum, with some but not all toxicants. The results also indicate that the different modes of action of the two c hemicals may account for the difference in the serum carboxylesterase activity of the experimental animals.