Publication: Hepatocyte nuclear phenotype, the cross-talk between anabolic androgenic steroids and exercise in transgenic mice
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Date
2008
Authors
Fontana, Karina ; Aldrovani, Marcela ; Paoli, Flávia de ; Oliveira, Helena C.F. ; Campos Vidal, Benedicto de ; da Cruz Hoflingl, M.A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The growing and indiscriminate use of high
doses of anabolic androgenic steroid (AAS) among
youth and athletes has raised serious concerns about its
hepatotoxic effects. Herein, the influence of AAS in the
nuclear phenotype of hepatocytes was investigated in
sedentary and trained mice heterozygous for the human
CETP (cholesteryl ester transfer protein) transgene and
for LDL-receptor null allele (CETP+/-LDLr+/-) by image
analysis. Five groups were assayed comprising treadmill
exercised (Ex) and sedentary (Sed) mice, administered
mesterolone (AAS) or gum arabic (GA) and a sedentary
blank control: G1(SedAAS), G2(SedGA), G3(ExAAS),
G4(ExGA), and G5(SedBL). To assess nuclear
phenotypes, the state of chromatin supraorganization,
DNA content and fragmentation (TUNEL assay), area
and perimeter of hepatocytes were determined in
Feulgen-stained liver imprints. In addition, the activity
of aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) hepatic transaminases were
measured. SedAAS-G1 showed the lowest chromatin
condensation and highest Feulgen-DNA content,
polyploid nuclei frequency, nuclear area and perimeter,
suggesting gene activation. Contrarily, ExAAS-G3 showed a highest chromatin condensation, and a
significant decrease of Feulgen-DNA content and
decreased frequency of polyploid nuclei, which suggest
gene silencing. Image analysis of the nuclear phenotype
offered a coherent descriptive picture of the changing
patterns of chromatin organization, which were shown to
be congruent with the levels of Feulgen-DNA content, geometric nuclear parameters and hepatocyte activity. In
this study, the image analysis permitted the monitoring
of the nuclear response to mesterolone and physical
exercise action in liver cells, the molecular mechanism
of which is in prospect.
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