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) pa rtially prevented necrogenic effects of this compound at 24 hr. TFPro has only minor effects on the covalent binding (CB) of CCl4-reactive m etabolites to cellular constituents and even an enhancing action on CC l4-promoted lipid peroxidation (LP). Determination of TFPro levels in liver 1 and 3 hr after administration by gas chromatography/mass spect rometry showed its presence in that tissue at concentrations well abov e those needed for calmodulin (CaM) inhibitory effects of this drug. T FPro lowered body temperature in CCl4-treated animals during the 24-hr observation period. Protective effects of TFPro at 6 or 10 hr, when m ost of the CB and all of the LP has already occurred, suggest but do n ot prove a role for CaM in late stages of CCl4-induced necrogenic effe cts. Decreases in the body temperature of CCl4-poisoned animals provok ed by TFPro might also play a role in the preventive actions of this d rug. (C) 1995 Academic Press,Inc.