Influence of lipid peroxidation on lipoprotein secretion by isolated hepatocytes

Isolated rat liver cells have been exposed to 3 different lipid peroxidation-inducing agents, CCl₄, FeCl₃ and cumene hydroperoxide, and the rates of malonaldehyde production and of lipoprotein secretion have been compared. Results indicate that it is possible to induce a high degree of lipid peroxidation without inducing strong changes in lipoprotein secretion. Only in CCl₄-poisoned hepatocytes is lipoprotein secretion strongly impaired. In this experimental condition, the effect of free radical scavengers, or inhibitors of lipid peroxidation, has been studied; the degree of covalent binding of CCl₄ metabolites to hepatocyte proteins, as well as the behavior of both lipid peroxidation and lipoprotein secretion, have been evaluated. Promethazine and propyl gallate prevented malonaldehyde production, but neither agent reduced covalent binding nor improved secretion. Menadione, on the contrary, besides inhibiting malonaldehyde production, decreased covalent binding and protected against the impairment of secretion. These data lead to the conclusion that covalent binding of CCl₄ metabolites, rather than lipid peroxidation products, accounts for the derangement of lipoprotein secretion in CCl₄-poisoned liver cells. Presented in part at the ISF-AOCS World Congress, New York, April 1980.