Publication: Acute cardiotoxicity induced by doxorubicin in right ventricle is associated with increase of oxidative stress and apoptosis in rats
Authors
Anghel, N. ; Herman, H. ; Balta, C. ; Rosu, M. ; Stan, M.S. ; Nita, D. ; Ivan, A. ; Galajda, Z. ; Ardelean, A. ; Dinischiotu, A. ; Hermenean, A.
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Publisher
Universidad de Murcia. Departamento de BiologĂa Celular e HistologĂa
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DOI
DOI: 10.14670/HH-11-932
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info:eu-repo/semantics/article
Description
Abstract
Doxorubicin (DOX) is one of the most
effective chemotherapeutic agents, but its efficiency is
seriously limited by the risk of developing
cardiomyopathy. The most recognized cardiotoxic effect
is left ventricular (LF) dysfunction, but MRI and
echocardiography data demonstrated significant right
ventricle (RV) function impairment. In order to clarify
this aspect, the present study investigated the potential of
DOX to induce acute RV cardiotoxicity at the same time
as LV impairment. Rats were intraperitoneally (i.p.)
injected with a single dose of 15 mg/kg DOX. DOXtreated rats were characterized by decreased body and
heart weights, elevated levels of creatine kinase (CKMB) and lactate dehydrogenase (LDH) activities
compared to controls. Biochemical analyses on RV
tissue revealed that the level of malondialdehyde (MDA)
was significant increased (p<0.05) and activities of
catalase (CAT), glutathione reductase (GR), glutathione
peroxidase (GPX) antioxidant enzymes were decreased
by 13%, 27% and 18%, respectively, compared to
control. Histopathogical and electron microscopic
studies revealed DOX-induced damage in both ventricles
and an increase of interstitial collagen fibers compared
to controls (p<0.001), whereas immunohistochemical
analysis showed weak and irregular desmin expression.
Furthermore, mitochondrion-induced apoptotic pathways
were also activated in both ventricles, as reflected by the
up-regulation of Bax/Bcl-2 mRNA expression ratio
(p<0.001) and increase of Bax and caspase-3 protein
expression, as well as by the significant elevation of
TUNEL positive nuclei, compared to controls (p<0.001).
The results showed that DOX exerted RV toxic effects at
the same time as those reported in the LV, which might
be mediated through the mitochondrial-dependent
apoptosis.
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