Early biochemical alterations in liver mitochondria from carbon tetrachloride poisoned rats.

Covalent binding of reactive metabolites of 14CCl4 were found 1 or 3 h after treatment with the solvent in the lipid and protein fractions of highly purified liver mitochondrial of rats. Most of the label was found in the phospholipid (PL) fraction, much less in cholesterol esters (ChE), and only minor quantities in other lipids. The reactive metabolites of 14CCl4 activated by isolated mitochondria interact mostly with ChE and far less with PL and other fractions. Both in vivo and in vitro covalent binding to PL is decreasing in the following order: phosphatidylethanolamine greater than diphosphatidylglycerol greater than phosphatidylcholine greater than sphingomyelin greater than lysophosphatidyl choline. No evidence of lipid peroxidation was found in liver mitochondrial lipids in the first 6 h and only a slight tendency of decrease in arachidonic acid concentration at 24 h. The incorporation of [14C] leucine in mitochondrial, microsomal or cytosolic proteins decreased as early as 1 h after treatment. These results, in agreement with previous reports suggest the existence of multiple sites in liver cells for the activation of CCl4. The transport of altered phospholipids and proteins and the inhibition of protein synthesis might contribute to the propagation of damage from the endoplasmic reticulum to other organelles.