The Egyptian Heart Journal,
Год журнала:
2025,
Номер
77(1)
Опубликована: Март 10, 2025
Abstract
Background
Cardiomyopathy
is
a
heterogeneous
group
of
myocardial
disorders
characterized
by
structural
and
functional
abnormalities
the
heart
muscle.
It
classified
into
primary
(genetic,
mixed,
or
acquired)
secondary
categories,
resulting
in
various
phenotypes
including
dilated,
hypertrophic,
restrictive
patterns.
Hypertrophic
cardiomyopathy,
most
common
form,
can
cause
exertional
dyspnea,
presyncope,
sudden
cardiac
death.
Dilated
cardiomyopathy
typically
presents
with
failure
symptoms,
while
rarer
often
associated
systemic
diseases.
Diagnosis
involves
comprehensive
evaluation
history,
physical
examination,
electrocardiography,
echocardiography.
Treatment
options
range
from
pharmacotherapy
lifestyle
modifications
to
implantable
cardioverter-defibrillators
transplantation
refractory
cases.
Main
body
Anthracyclines,
particularly
doxorubicin,
have
emerged
as
crucial
components
cancer
treatment,
demonstrating
significant
antitumor
activity
across
malignancies.
These
drugs
become
standard
numerous
chemotherapy
regimens,
improving
patient
outcomes.
However,
their
use
severe
cardiotoxicity,
failure.
The
mechanisms
anthracycline
action
toxicity
are
complex,
involving
DNA
damage,
iron-mediated
free
radical
production,
disruption
cardiovascular
homeostasis.
Doxorubicin-induced
(DIC)
complication
treatment
poor
prognosis
limited
effective
treatments.
pathophysiology
DIC
multiple
mechanisms,
oxidative
stress,
inflammation,
mitochondrial
calcium
homeostasis
disorder.
Despite
extensive
research,
no
for
established
currently
available.
Dexrazoxane
only
FDA-approved
protective
agent,
but
it
has
limitations.
Recent
studies
explored
potential
therapeutic
approaches,
natural
drugs,
endogenous
substances,
new
dosage
forms,
herbal
medicines.
lack
experimental
models
incorporating
pre-existing
limits
understanding
efficacy.
Conclusion
Cardiomyopathy,
whether
secondary,
poses
clinical
challenge
due
its
varying
etiologies
advanced
stages.
Anthracycline-induced
chemotherapy,
doxorubicin
being
notable
contributor.
advancements
therapies,
cardiotoxic
effects
anthracyclines
necessitate
further
investigation
preventive
strategies
interventions
improve
Drug Design Development and Therapy,
Год журнала:
2025,
Номер
Volume 19, С. 1067 - 1081
Опубликована: Фев. 1, 2025
Doxorubicin
(DOX),
an
anthracycline
antibiotic,
has
limited
clinical
use
due
to
its
pronounced
cardiotoxicity.
Irisin,
a
myokine
known
for
metabolic
regulation,
shown
therapeutic
effects
on
cardiovascular
disease.
This
study
investigates
the
potential
cardioprotective
function
of
irisin
in
reducing
cardiac
injury
induced
by
DOX.
In
vitro,
H9c2
cells
were
pretreated
with
(20
nM)
24
hours
before
exposure
DOX
(1
μM).
vivo,
C57BL/6
mice
administered
(5
mg/kg/week,
i.p.)
4
weeks,
reaching
cumulative
dose
20
mg/kg.
Irisin
mg/kg/
3
days,
was
both
7
days
prior
and
during
injection.Cardiac
evaluated
echocardiography,
histology
assessed
using
HE,
WGA,
Masson
staining.
Myocardial
markers
quantified
ELISA,
apoptosis
analyzed
via
TUNEL
Oxidative
stress
determined
measuring
antioxidase
activity,
MDA
GSH
levels,
DHE
staining,
while
mitochondrial
superoxide
production
MitoSOX
Red.
Mitochondrial
morphology
transmission
electron
microscopy
Seahorse
analysis,
respectively
Inflammatory
cytokines
serum
cell
supernatants.
The
role
PERK-eIF2α-ATF4
pathway
mediated
investigated
Western
blot.
Using
adeno-associated
virus
serotype-9
carrying
mouse
FNDC5
shRNA
(AAV9-shFNDC5)
further
validated
protective
DOX-induced
myocardial
injury.
reduced
dysfunction
fibrosis.
Moreover,
mitigated
oxidative
inflammation
through
inhibiting
activated
DOX,
thus
preserving
function.
While
knockdown
exacerbated
heart
activation,
which
partially
reversed
irisin.
mitigates
modulating
pathway,
highlighting
as
prospective
approach
combating
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 8, 2025
Abstract
Doxorubicin
(DOX)
is
used
to
treat
a
variety
of
malignancies;
however,
its
cardiotoxicity
limits
effectiveness.
Shikimic
acid
(SA)
showed
several
promising
biomedical
applications.
This
study
investigated
the
protective
effect
SA
on
DOX-induced
in
male
rats.
The
ADMETlab
2.0
web
server
was
predict
pharmacokinetic
properties
SA.
Molecular
docking
studies
were
conducted
using
AutoDock
Vina.
Fifty
rats
divided
into
4
groups
(
n
=
10);
G1
negative
control;
G2
injected
with
mg/kg
DOX
intraperitoneally
(i.p.)
once
week
for
month;
G3
gavaged
by
1/10
LD
50
(280
mg/kg)
daily
month,
and
G4
as
G3.
After
hematological,
biochemical,
molecular,
histopathological
investigations
assessed.
results
that
treatment
led
significant
amelioration
restoring
inflammatory
biomarkers,
antioxidant
gene
expression,
cardiac
alterations.
Importantly,
impact
against
DOX-promoted
deterioration
targeting
Nrf-2/Keap-1/HO-1/NQO-1
signaling
pathway,
which
turn
induces
agents.
These
findings
suggest
could
potentially
mitigate
toxicity
during
DOX-based
chemotherapy.
Doxorubicin
(DOX)
is
used
as
a
chemotherapeutic
drug
for
treating
cancer.
Nevertheless,
it
causes
damage
to
the
heart
by
activating
inflammatory
pathways,
resulting
in
cardiotoxicity.
Imbalance
cytokine
production
crucial
component
that
might
trigger
initiation
of
processes.
Inflammatory
cytokines
could
be
targeted
therapies
against
cardiovascular
diseases
(CVDs).
Interleukin-17A
(IL-17A)
promotes
inflammation
and
stimulates
harmful
immunological
reactions.
The
objective
study
was
determine
efficacy
secukinumab
(SEC),
completely
human
monoclonal
IgG1/κ
antibody
targets
IL-17A,
ameliorating
DOX-induced
cardiotoxicity
(DIC).
We
administered
2.5
mg/kg
DOX
intraperitoneally
male
Wistar
rats
three
times
week
2
weeks
simultaneously
0.9
SEC
along
with
injection
duration
two
weeks.
findings
indicated
induced
tissue,
significant
rise
indicators
(P
<
0.001),
well
oxidative
stress
inflammation.
DIC
may
have
arisen
from
DOX's
activation
Pyrin
domain
containing
3
(NLRP3)
inflammasome
nuclear
factor
kappa
beta
(NF-κB)
pathway.
co-administration
successfully
reversed
all
abnormalities
restoring
cardiac
functions
their
baseline
levels,
decreasing
levels
mediators
such
IL-17A
interleukin-1β
(IL-1β),
improving
reducing
malondialdehyde
(MDA)
increasing
reduced
glutathione
(GSH).
Furthermore,
mitigated
heightened
NF-κB/NLRP3
pathway
caused
DOX.
This
shows
neutralization
can
prevent
regulating
NF-κB/NLRP3/Caspase-1/IL-1β
potential
therapeutic
target
CVDs.
The Egyptian Heart Journal,
Год журнала:
2025,
Номер
77(1)
Опубликована: Март 10, 2025
Abstract
Background
Cardiomyopathy
is
a
heterogeneous
group
of
myocardial
disorders
characterized
by
structural
and
functional
abnormalities
the
heart
muscle.
It
classified
into
primary
(genetic,
mixed,
or
acquired)
secondary
categories,
resulting
in
various
phenotypes
including
dilated,
hypertrophic,
restrictive
patterns.
Hypertrophic
cardiomyopathy,
most
common
form,
can
cause
exertional
dyspnea,
presyncope,
sudden
cardiac
death.
Dilated
cardiomyopathy
typically
presents
with
failure
symptoms,
while
rarer
often
associated
systemic
diseases.
Diagnosis
involves
comprehensive
evaluation
history,
physical
examination,
electrocardiography,
echocardiography.
Treatment
options
range
from
pharmacotherapy
lifestyle
modifications
to
implantable
cardioverter-defibrillators
transplantation
refractory
cases.
Main
body
Anthracyclines,
particularly
doxorubicin,
have
emerged
as
crucial
components
cancer
treatment,
demonstrating
significant
antitumor
activity
across
malignancies.
These
drugs
become
standard
numerous
chemotherapy
regimens,
improving
patient
outcomes.
However,
their
use
severe
cardiotoxicity,
failure.
The
mechanisms
anthracycline
action
toxicity
are
complex,
involving
DNA
damage,
iron-mediated
free
radical
production,
disruption
cardiovascular
homeostasis.
Doxorubicin-induced
(DIC)
complication
treatment
poor
prognosis
limited
effective
treatments.
pathophysiology
DIC
multiple
mechanisms,
oxidative
stress,
inflammation,
mitochondrial
calcium
homeostasis
disorder.
Despite
extensive
research,
no
for
established
currently
available.
Dexrazoxane
only
FDA-approved
protective
agent,
but
it
has
limitations.
Recent
studies
explored
potential
therapeutic
approaches,
natural
drugs,
endogenous
substances,
new
dosage
forms,
herbal
medicines.
lack
experimental
models
incorporating
pre-existing
limits
understanding
efficacy.
Conclusion
Cardiomyopathy,
whether
secondary,
poses
clinical
challenge
due
its
varying
etiologies
advanced
stages.
Anthracycline-induced
chemotherapy,
doxorubicin
being
notable
contributor.
advancements
therapies,
cardiotoxic
effects
anthracyclines
necessitate
further
investigation
preventive
strategies
interventions
improve
