Zonal differences in lipoprotein formation in the thioacetamide-in-duced micronodular-cirrhotic rat liver

Summary The aim of the studies was to answer the question to what extent thioacetamide-induced structural alterations of hepatic architecture leading to fibrosis and micronodular pseudolobuli affect the formation of very low density lipoproteins and the zonation of lipoprotein metabolism observed in normal and acutely injured livers. Therefore, the number of the VLDL particles/Golgi complex and the relative specific volume of Golgi complexes as well as the number and relative specific volume of VLDL-filled vesicles was determined in lobular and nodular zones of normal and the micronodular-cirrhotic livers, respectively. The perinodular and centrinodular regions were morphometrically analysed in nodules with diameters between 0.3 and 0.5 mm. — Generally, in thioacetamide-induced micronodular liver cirrhosis a zonality was observed with respect to the amount of VLDL particles as well as the number and volume of organelles involved in the formation and secretion of hepatic lipoproteins. However, the number of VLDL particles/Golgi complex was significantly reduced to 52 % in the centrinodular and to 71 % in the perinodular region of cirrhotic livers when compared with the corresponding periportal and perivenous area, respectively. Furthermore, the relative specific volume of the Golgi complexes markedly increased in the perinodular region, thus abolishing the zonal difference observed in the controls. In studies with colchicine used to block the secretion of VLDL particles the number of light secretory vesicles was drastically lowered from 45.1 ± 4.9/100 μm 2 in the periportal region and 36.2 ± 5.1/100 μm 2 in the perivenous one of controls to 17 ± 3/100 μm 2 in the centrinodular zone and to 9.3 ± 1.9/ 100 μm 2 in the perinodular one of cirrhotic livers, respectively. When considering the increase in the relative specific volume of the light secretory vesicles in the perinodular region of cirrhotic livers and the reduction of their number/ 100 μm 2 the volume of the vesicles must be markedly augmented. These changes were connected with an enlargement of the volume of dark secretory vesicles in the perinodular region of cirrhotic livers. Serum VLDL of the micronodular-cirrhotic animals exhibited a marked size hetero- geneity. On the background of the reduced VLDL production of cirrhotic livers reported recently by us the data indicate a premature degradation of VLDL particles in micronodular-cirrhotic livers, particularly in the perinodular zone.