Clasmatosis and proliferation of hepatocytes at the initial stages of experimental hypercholesterolemia in rabbits

Abstract

Profound dystrophic changes, which involved granulocytes and were associated with acute inflammatory reaction, were observed in rabbit liver at the initial stage of experimental hypercholesterolemia. It was suggested that "acute phase" is important for the formation of a modified lipoprotein with autoantigenic properties. Key Words: hypercholesterolemia; C-reactive protein; leukocyte decationization; clasmatosisIt was hypothesized that modified apoprotein Bcontaining lipoprotein (apoB-LP) with autoantigenic activity [ 1,7] is an important factor of atherosclerosis [5]. Proceeding from this hypothesis, one can regard atherogenesis as a local immune inflammation [2]. The vascular wall is a target organ in which the modifications occurring in the organism are realized. The liver is the major organ that synthesizes and catabolizes various LP which were isolated from aortic intilna [1]. Hepatocytes are the major cell type producing the acute inflammation proteins C-reactive protein (CRP) and serum amyloid P (SAP). These proteins play an important role in the imnmnoregulation and activation of granular and agranular leukocytes [4]. A relationship mediated by the phospholipid groups has been established between the acute-phase proteins and low-and very low-density LP [6]. As we are aware, morphological manifestations of structural and functional modifications occurring in hepatocytes during the development of hypercholesterolemia have not been investigated except fatty dystrophy of the liver. Our objective was to analyze the morphofnnctional changes in the liver at the initial stages of experimental hypercholesterolemia when modified apoB-LP emerge in peripheral blood and the concentration of CRP and SAP increase. MATERIALS AND METHODSExperiments were performed on 28 male rabbits weighing 2.8-3.0 kg. Hypercholesterolemia was induced by feeding the animals with cholesterol dissolved in sunflower oil (200 mg cholesterol/kg body weight) through a gastric tube 5 times a week. Sermn lipids were measured in a Technicon AA-II analyzer before and on days 2, 4, 7, and 14 of hypercholesterolemia. The CRP and SAP contents were determined by light absorbance changes after the precipitation reaction.Blood smears as well as liver prints and sections were stained for cationic proteins by the method of V. E. Pigarevskii. Liver sections were stained for lipids with oil red O and with hematoxylin and eosin, hmnunohistochemical investigations were performed with the use of anti-CRP and anti-SAP polyclonal antibodies. Proliferative activity of hepatocytes was determined after a single intravenous injection of the synthetic analog of thy-0007-4888/98/0010-01059520.00 9Kluwer Ac~tdem[c/PlemmJ Publisher.~