The presence of optically clear spaces in the cytoplasm of parenchymal cells of
glucocorticoids treated liver sections are interpreted in various ways. Hill and Broke
(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
guts. 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 henatoxylin-rosin
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 glucocorticsids 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.
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