Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis.
Trifluoperazine (TFP) (50 mg/kg ip) administration to rats 6 or 10 hr after CCl4 (1 ml/kg ip in olive oil) significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as evidenced by either histology or electron microscopy. TFP given 6 hr after CCl4 significantly decreased the CCl4-induced increases in liver calcium content. TFP raised four to five times the liver glycogen content in control rats but was unable to modify decreased glycogen content of CCl4 poisoned animals. TFP administration increased phospholipid and protein synthesis as evidenced by studies on 32P incorporation into microsomal phospholipid and by experiments on [14C]leucine incorporation in microsomal protein fractions from control rat livers. No significant changes were observed in microsomal phospholipid degradation as studied by decay of label from 32P-prelabeled microsomal lipids or in increased protein degradation as evidenced by decay of label from [14C-guanidino]arginine-prelabeled microsomal proteins found in livers of control rats after TFP treatment. Electron microscopy observations of liver from control animals treated with TFP evidenced accumulation of glycogen in areas close to smooth endoplasmic reticulum (SER); large Golgi areas with an abundant number of lysosomes, and minor dilatation effects on the rough endoplasmic reticulum (RER) and nuclear membrane. Results suggest that TFP preventive effects might be due to the anticalmodulin actions of this drug.
Bernacchi
A S
AS
Centro de Investigaciones Toxicológicas, CEITOX-CITEFA/CONICET, Buenos Aires, Argentina.
Fernández
G
G
Villarruel
M C
MC
de Ferreyra
E C
EC
de Castro
C R
CR
de Fenos
O M
OM
Castro
J A
JA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005234:Fatty Liver / Q000139:chemically induced; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology / Q000627:therapeutic use*
D002147:Calmodulin; D008112:Liver Glycogen; D014268:Trifluoperazine; D002118:Calcium