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.
Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, Buenos Aires, Argentina.
E C
EC
de Ferreyra
A S
AS
Bernacchi
M F
MF
San Martin
G D
GD
Castro
J A
JA
Castro
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D014273:Triflupromazine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D002147:Calmodulin; D014273:Triflupromazine