Journal of Lipid Research, Vol 16, 143-150, Copyright © 1975 by Lipid Research, Inc.
Hepatic fine structure in young and aging rats treated with oxandrolone: a morphometric study
DL Schmucker and AL Jones
Hepatic fine structural alterations induced by shortterm administration of
the hypolipidemic drug oxandrolone were evaluated using morphometric
techniques. These changes are described in the livers of normolipidemic
young adult and hyperlipidemic retired breeder male rats. Retired breeder
rats, characterized by hyperlipidemia and a high incidence of
arteriosclerosis, are thought to undergo premature aging. A previous
morphometric study has shown that the hepatocytes of retired breeder rats
are larger, contain a greater volume fraction of lysosomes, and have
significantly less smooth-surfaced endoplasmic reticulum than those of
young adult rats. However, after oxandrolone administration, the livers of
these two animal groups were no longer distinguishable on the basis of
these morphometric parameters. Unlike a number of other hypolipidemic
drugs, oxandrolone does not induce a marked proliferation of hepatic
microbodies. The effect of oxandrolone on the livers of prematurely aging
rats suggests that the age-related fine structural changes are not the
result of irreversible alterations in the genome or
translation-transcription apparatus but may actually represent secondary
reactions to extrahepatic and/or endocrine metabolic changes. The
relationship between (1) aging and hyperlipidemia and (2) aging and the
reduced hepatic capacity to metabolize drugs suggest a need to evaluate the
effects of lipid-lowering drugs on the livers of old as well as young
animal models.
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