Publication: Daunorubicin does not induce
immunohistochemically detectable endothelial
dysfunction in rabbit aorta and femoral artery
Authors
Nachtigal, Petr ; Šterba, Martin ; Popelová, Olga ; Vecerova, lenka ; Kudláčková, Zdeňka ; Jirkovský, Eduard ; Geršl, Vladimír
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Anthracyclines are one of the most effective
anticancer drugs ever developed, but their clinical use
has been hampered by the risk of severe cardiotoxicity.
In this study, we investigated whether rabbits exposed to
a different cumulative dose of anthracycline suffer from
immunohistochemically detectable vascular toxicity and
endothelial dysfunction.
Daunorubicin (3 mg/kg, i.e. 50 mg/m2) was
administered i.v. to rabbits once weekly for 1-10 weeks
to reach different cumulative doses of the drug (50-500
mg/m2), while control rabbits received saline. The
rabbits were sacrificed either 24 hours or 7 days after
reaching each particular cumulative dose, and aortas and
right femoral arteries were collected for immunohistochemical
analysis.
Immunohistochemical analysis showed ICAM-1
staining in many aortas from both saline and
daunorubicin-treated rabbits without any relationship to
the anthracycline treatment. On the contrary, unlike in
the lipopolysaccharide-treated or hypercholesterolemic
rabbits, no distinct immunoreactivity for other markers
of inflammation, oxidative and nitrosative stress
(VCAM-1, 4-HNE, iNOS and nitrotyrosine) were
detected in aortas and femoral arteries from either
control or daunorubicin-treated animals. No relationship
to the cumulative dose of the drug or post-expose set up
of harvesting was found.
In this study, we have demonstrated that
daunorubicin does not induce gross histopathological
changes in the studied arteries and it fails to induce immunohistochemically detectable endothelial
dysfunction. Thus, we propose that endothelial cells are
much less susceptible to anthracycline toxicity than
cardiac myocytes. In addition, our data suggest that
vascular toxicity of anthracyclines plays rather a minor
role in the cardiovascular complications of anthracycline
chemotherapy.
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