Late preventive effects of trifluoperazine on carbon tetrachloride-induced hepatic necrosis

Journal Article · Tue Apr 01 04:00:00 EST 1986 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(86)90306-6· OSTI ID:5674430

Villarruel, M C; Fernandez, G; de Ferreyra, E C; de Fenos, O M; Castro, J A

As a very preliminary test for a possible role of calmodulin in CCl/sub 4/-induced hepatic injury, we studied the effects of the anticalmodulin drug trifluoperazine (TFP) on several deleterious actions of CCl/sub 4/ on the liver. TFP administrated 30 min before or 6 or 10 hr after CCl/sub 4/ significantly prevented hepatic necrosis induced by the hepatotoxin at 24 hr but not at 72 hr. TFP did not modify the CCl/sub 4/ concentrations reaching the liver, or the intensity of the covalent binding of CCl/sub 4/-reactive metabolites to hepatic microsomal proteins or lipids or the CCl/sub 4/-induced cytochrome P-450 and glucose 6 phosphatase destruction. TFP administration decreased body temperature between 0 and 1 degree C in controls and between 1.2 and 3.5 degrees C in CCl/sub 4/-treated animals during the 24-hr observation period. When TFP-treated CCl/sub 4/-poisoned animals were kept normothermic, protective effects were eliminated. One possibility is that the protective effect of TFP might be due to a nonspecific action related to decreased body temperature. Alternatively, prevention might result from TFP inhibition of a late-occurring process critical for CCl/sub 4/-induced cell necrosis requiring calmodulin participation. If this alternative were in operation, protective consequences of this inhibitory effect of TFP should be either canceled or counteracted in the normothermic TFP + CCl/sub 4/-treated animal.

• Research Organization: Centro de Investigaciones Toxicologicas (CEITOX), CITEFA/CONICET, Provincia de Buenos Aires, Argentina
• OSTI ID: 5674430
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 2; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AZINES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BODY TEMPERATURE
CARBON TETRACHLORIDE
CHLORINATED ALIPHATIC HYDROCARBONS
COVALENCE
DIGESTIVE SYSTEM
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
KINETICS
LIPIDS
LIVER
MAMMALS
METABOLITES
NECROSIS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PHENOTHIAZINES
RATS
REACTION KINETICS
RODENTS
TOXICITY
VERTEBRATES