Hepatocyte damage induced by carbon tetrachloride: Inhibited lipoprotein secretion and changed lipoprotein composition

Changes of lipoprotein secretion and composition in response to CCl4 treatm ent were studied in monolayer cultures of rat primary hepatocytes. (1) CCl4 decreased secretion of very low density lipoproteins (VLDL) by abo ut 85%, while high density lipoprotein (HDL) secretion was less affected (a bout 40%). The effect was concentration-dependent. (2) CCl4 significantly i nhibited secretion of VLDL- and HDL-associated triglycerides and cholestero l esters. VLDL- and HDL-associated cholesterol was not affected, while secr etion of phospholipids was increased. (3) Hepatocytes secreted the apolipop roteins B-48, B-100, E, C, and A-I. CCl4 reduced secretion of apoproteins a ssociated with VLDL by almost 20%, and by about 75% when associated with HD L. The de novo synthesis of apolipoproteins was attenuated by CCl4. (4) CCl 4 caused variations in the apolipoprotein composition in VLDL and HDL. CCl4 intoxication of the liver affected the morphology and/or function of t he lipoproteins, which drastically impaired their ability to act as transpo rt vehicles for lipids from the liver to the circulation.