Qualitative and quantitative changes in hepatic lipoprotein particles following acute injury of the rat liver induced by thioacetamide

Acute intoxication of the rat liver with a single dose of 100 mg thioacetamide (TAA)/kg body weight causes within 48 h a fatty liver and a heterogeneous reaction in the hepatocytes. This affects principally the centrilobular liver parenchymal cells (zone 3) and to a lesser extent the periportal ones (zone 1). Ultrastructural analysis was performed to determine to what extent the formation of lipid-carrying particles of the very low density type (VLDL) is changed in affected hepatocytes in zones 1 and 3. Being morphologically the most conspicuous site of VLDL processing, the Golgi complex was chosen for quantitation by measuring its volume, VLDL content and particle size. The concentration and composition of the liver lipids were determined, biochemically. After TAA treatment of the liver the number of Golgi-VLDL particles is significantly reduced to about 50% in both the lobular zones examined. In addition, distinct classes of size-modified Golgi-VLDL particles appear which show an abnormally wide size distribution pattern. In periportal hepatocytes the size distribution of Golgi-VLDL particles shows a clear shift towards smaller particles homogeneous in size (mean diameter 39 nm). In contrast, centrilobular hepatocytes contain particles of very heterogeneous size, the mean diameter of which is nearly doubled (77 nm). The decrease in VLDL particle number and their size modification induced by TAA is not accompanied by significant changes in the volume of the Golgi complex. Biochemical analysis showed that the accumulation of lipids in the TAA-treated liver, mainly evident morphologically as drop-like deposits in the central area of the liver lobules, is due to an increase in triglycerides (TG) by 23 mumol/g liver wet weight, which represents nearly 95% of the accumulated lipids. Despite the striking elevation of the absolute cholesterol ester (CHOL-E) content (2 mumol/g liver wet weight), this corresponds to only 5% of the newly accumulated lipids. Our electron optical and biochemical results support the suggestion that, in spite of the markedly different intralobular reaction of TAA-intoxicated hepatocytes, the formation of triglyceride-carrying particles is altered significantly in both lobular zones examined.