Trifluopromazine late preventive effects on carbon tetrachloride-induced liver necrosis.

Trifluopromazine (TFPro) administration to rats (50 mg/kg, ip) 30 min before or 6 or 10 hr after CCl4 treatment (1 ml/kg ip in olive oil) partially prevented necrogenic effects of this compound at 24 hr. TFPro has only minor effects on the covalent binding (CB) of CCl4-reactive metabolites to cellular constituents and even an enhancing action on CCl4-promoted lipid peroxidation (LP). Determination of TFPro levels in liver 1 and 3 hr after administration by gas chromatography/mass spectrometry showed its presence in that tissue at concentrations well above those needed for calmodulin (CaM) inhibitory effects of this drug. TFPro lowered body temperature in CCl4-treated animals during the 24-hr observation period. Protective effects of TFPro at 6 or 10 hr, when most of the CB and all of the LP has already occurred, suggest but do not prove a role for CaM in late stages of CCl4-induced necrogenic effects. Decreases in the body temperature of CCl4-poisoned animals provoked by TFPro might also play a role in the preventive actions of this drug.