Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis

The authors previously reported that trifluorperazine (TFP) administration 6 or 10 hr after CCl4 is able to partially prevent liver necrosis by the hepatotoxin at 24 hr. Preventive effect is not due to interference by TFP on CCl4 metabolic activation to CCl3 or its covalent binding to cellular components or of lipid peroxidation. Now the authors report that TFP administration 10 hr after CCl4 does not prevent calcium accumulation but increases glycogen content. Increases in glycogen are more marked in livers of animals receiving only TFP. Administration slightly stimulates 14C-leucine incorporation in liver proteins but it does not modify decay of radioactivity in (14C-guanidino) arginine prelabelled liver protein. TFP does not modify decay of radioactivity in 32P prelabelled phospholipid. Electron microscopy studies of livers from CCl4 poisoned rats receiving TFP 10 hr after the hepatoto toxin and sacrificed at 24 hr revealed the presence of glycogen granules in otherwise glycogen-depleted preparations. These preparations showed only slight dilatation of the endoplasmic reticulum or the perinuclear membrane and intact mitochondria. Results might suggest that TFP interaction with calmodulin might interfere with a process of propagation of CCl4-induced liver damage sparked by calcium accumulation and requiring the hormone for operation