SEQUENTIAL QUANTITATIVE ANALYSIS OF OVAL CELL PROLIFERATION IN THIOACETAMIDE TREATED RATS

Abstract

Oval cells are the progeny of facultative stem cells found in the periportal areas in response to liver injury in experimental animals and humans. The aims of this study were to describe the morphological, stereological and morphometric features of oval cells, and to compare them with those of bile duct cells and hepatocytes. It was also aimed to study the fate of oval cells by morphological and morphometric criteria. Rats were given thioacetamide to induce liver injury. The livers from experimental and control groups were processed routinely and stereological and morphometric analysis assessed using a computer image analysis system. Eight morphometric parameters were assessed in oval cells, bile duct cells and hepatocytes from control and experimental rats. Mitoses were observed in both oval cells and hepatocytes. Stereological area fraction analysis indicated that necrosis reached its maximum extent at 30 hours followed by regeneration and almost complete restoration of liver cell parenchyma at 132 hours. Oval cell proliferation reached a peak at 48-52 hours but was not apparent at 132 hours. Morphometric findings have shown increases in the nuclear diameter and nuclear area of oval cells with changes in the roundness and contours ratios of the nuclear membrane. It is concluded from this study that in thioacetamide treated rats, the liver responds to injury by bile ductal proliferation in the periportal areas which, accompanied by hepatocyte regeneration, leads to restoration of the hepatic parenchyma. At a subcellular morphological level the nuclei of oval cells showed a progressive change to a hepatocyte phenotype from that of a normal biliary cell, suggesting the differentiation of these cells into hepatocytes.