Abstract

The presence of optically clear spaces in the cytoplasm of parenchymal cells of glucocorticoids treated liver sections are interpreted in various ways. Hill and Droke (1963) attributed the hepatocellular ballooning induced by parenterally administered cortisone to lipid accumulation, while Kim et al. (1969) thought it was due to glycogen accumulation. But Gans and McEntee(1961) and Thompson et al. (1971) studied these ballooning cells with special histochemical methods and demonstrated that the material distending the cells was neither glycogen nor lipid, and they speculated that the contents are probably water or diluted proteinic solutions. The role of cortisone and other corticosteroids in producing these alterations is still unknown and requires further study. The present studiers are undertaken in an attempt to identify the nature of these ballooning cells induced by glucocorticoids by histochemical and electron, microscopic studies. Materials and Methods ; Male albino rabbits weighing around 2.0 kg. and male albino rats weighing around 200 gms. were used for the experiment and divided into the following groups, one normally controlled and another glucocorticoids treated, which was in turn subdivided into cortisone acetate, prednisolone, and dexamethasone treated groups. The cortisone acetate prednisolone and dexamethasone were injected intramuscularly in a dose of 12. 0 mg., 3. 0 mg., and 0.6 mg, per kg. of the body weight per day. The serum glucose vague was determined by the methods of Folin-Wu both in the normally controlled and glucocorticoids treated groups with the blood drawn immediately before the animals were killed. Four rabbits of the control group were killed on the first, fifth and tenth day of the experiment and four rabbits of the glucocorticoids treated group on the 1st, 2nd, 3rd, 4th, 5th, 7th, and l0th day and two albino rats from each group on 1st, 5th and l0th day. Overall histologic alterations were observed by routine hematoxylin-erosin staining technic, and PAS, D-PAS staining for mucopolysaccharides and glycogen, and Oil red-O staining for lipid demonstration were applied. For the electron microscopic examination the tissue was filed twice, first with 4% glutaraldehyde in phosphate buffer of PH 7.4 followed by 1% osmium tetraoxide in phosphate buffer of pH 7 4 for 2-hours, and embedded in Epon 812 following dehydration with graded alcohol. Sections were made with a glass knife of 400 to 500Å thickness and stained with uranyl acetate and lead hydroxide. Observation was made with Hitachi II-E model electron microscope.
Results
and Discussion ; The adiministration of glucocorticoids to rabbits and albino rats resulted in a slight decrease in body weight, whereas the liver weight significantly increased in the animals receiving glucocorticoids. But the water content of the liver remained unchanged. Histological examination of rabbits receiving glucocorcoticoids revealed a marked ballooning and vesicular appearance of the hepatic cells in the mid-zonal and periportal areas of hepatic lobules. The maximal intensity of ballooning and vesicular cytoplasmic changes in liver was observed in dexamethasone treated rabbits followed by prednisolone and cortisone acetate treated rabbits. Special stains and electron microscopic studies demonstrated that the material distending the hepatic cells was glycogen only in the rabbits. But in the rats, the ballooning and vesicular changes of the hepatic cells were very mild in comparison to the rabbits, and moreover special stains and electron microscopic studies demonstrated that the nature of the ballooning cells was the result of a combination of glycogen with lipid accumulation. The glycogen accumulation was accompanied by marked proliferation of SER, but the proliferation of SER appeared to be the secondary to glycogen accumulation. After a maximal SER proliferation, further glycogen accumulation was not demonstrable in spite of repeated glucocorticoids treatment. Summary ; The nature of hepatocellular ballooning induced by glucocorticoids treatment is due solely to glycogen accumulation in the rabbits, while it is due to a combination of glycogen with lipid accumulation in the rats, indicating that there existed a species difference in the reaction to glucocorticcids. The marked SER proliferation without glycogen accumulation appeared to be the result of glycogen accumulation rather than to be a cause, and more likely concerned with glycogenolysis.