Theranostics,
Год журнала:
2023,
Номер
13(15), С. 5435 - 5451
Опубликована: Янв. 1, 2023
Doxorubicin
(Dox)
is
an
effective
anticancer
molecule,
but
its
clinical
efficacy
limited
by
strong
cardiotoxic
side
effects.
Lysosomal
dysfunction
has
recently
been
proposed
as
a
new
mechanism
of
Dox-induced
cardiomyopathy.
However,
to
date,
there
paucity
therapeutic
approaches
capable
restoring
lysosomal
acidification
and
function
in
the
heart.
Methods:
We
designed
novel
poly(lactic-co-glycolic
acid)
(PLGA)-grafted
silica
nanoparticles
(NPs)
investigated
their
potential
primary
prevention
Dox
cardiotoxicity
cardiomyocytes
mice.
Results:
showed
that
NPs-PLGA
internalized
rapidly
accumulated
inside
lysosomes.
Mechanistically,
restored
presence
doxorubicin
or
bafilomycin
A1,
thereby
improving
autophagic
flux.
Importantly,
mitigated
Dox-related
mitochondrial
oxidative
stress,
two
main
mechanisms
cardiotoxicity.
In
vivo,
inhalation
led
rapid
targeting
myocardium,
which
prevented
adverse
remodeling
cardiac
Conclusion:
Our
findings
demonstrate
pivotal
role
for
cardiomyopathy
highlight
first
time
pulmonary-driven
administration
promising
strategy
against
anthracycline
Redox Biology,
Год журнала:
2024,
Номер
72, С. 103129 - 103129
Опубликована: Март 19, 2024
Doxorubicin
is
a
powerful
chemotherapeutic
agent
for
cancer,
whose
use
limited
due
to
its
potential
cardiotoxicity.
Semaglutide
(SEMA),
novel
analog
of
glucagon-like
peptide-1
(GLP-1),
has
received
widespread
attention
the
treatment
diabetes.
However,
increasing
evidence
highlighted
therapeutic
benefits
on
cardiac
function.
Therefore,
objective
this
study
was
examine
efficacy
semaglutide
in
ameliorating
doxorubicin-induced
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115654 - 115654
Опубликована: Окт. 6, 2023
Doxorubicin
(DOX)
is
a
commonly
used
chemotherapy
drug
widely
applied
in
various
cancers
such
as
breast
cancer,
leukemia,
and
sarcomas.
However,
its
usage
limited
by
cardiotoxicity.
Additionally,
the
cardiac
toxicity
of
DOX
accumulates
with
dose
duration,
making
it
imperative
to
identify
therapeutic
targets
for
DOX-induced
cardiomyopathy
(DIC).
It
has
been
reported
that
miRNAs
are
involved
progression
DIC.
Mir-34a-5p
identified
an
early
diagnostic
marker
While
studies
have
shown
involvement
mir-34a-5p
DIC
apoptosis,
not
validated
animal
models,
nor
potential
improvement
inhibiting
confirmed.
Autophagy
pyroptosis
key
factors
development
can
serve
treatment.
In
this
study,
we
found
was
upregulated
heart
after
treatment
inhibition
mir-34-5p
reduced
autophagy
We
also
inhibited
regulating
reducing
mitochondrial
reactive
oxygen
species.
Moreover,
Sirtuin3
(Sirt3)
target
gene
using
double-luciferase
reporter
assay.
overexpression
Sirt3
alleviating
autophagy.
Our
research
findings
suggest
beneficial
role
This
provides
prospects
treating
Theranostics,
Год журнала:
2024,
Номер
14(9), С. 3719 - 3738
Опубликована: Янв. 1, 2024
Autophagy
dysregulation
is
known
to
be
a
mechanism
of
doxorubicin
(DOX)-induced
cardiotoxicity
(DIC).
Mitochondrial-Endoplasmic
Reticulum
Contacts
(MERCs)
are
where
autophagy
initiates
and
autophagosomes
form.
However,
the
role
MERCs
in
DIC
remains
elusive.
FUNDC1
tethering
protein
MERCs.
We
aim
investigate
effect
DOX
on
cardiomyocytes
explore
whether
it
involved
dysregulated
DIC.
Journal of Personalized Medicine,
Год журнала:
2023,
Номер
13(4), С. 649 - 649
Опубликована: Апрель 10, 2023
(1)
Background:
Doxorubicin
(DOX)
is
extensively
used
for
cancer
treatments;
however,
its
clinical
application
limited
because
of
cardiotoxic
adverse
effects.
A
combination
DOX
and
agents
with
cardioprotective
properties
an
effective
strategy
to
ameliorate
DOX-related
cardiotoxicity.
Polyphenolic
compounds
are
ideal
the
investigation
novel
agents.
Chlorogenic
acid
(CGA),
essential
dietary
polyphenol
found
in
plants,
has
been
previously
reported
exert
antioxidant,
cardioprotective,
antiapoptotic
properties.
The
current
research
evaluated
CGA’s
vivo
DOX-induced
cardiotoxicity
probable
mechanisms
underlying
this
protection.
(2)
Methods:
were
investigated
rats
that
treated
CGA
(100
mg/kg,
p.o.)
fourteen
days.
experimental
model
was
induced
a
single
intraperitoneal
(15
mg/kg
i.p.)
injection
on
10th
day.
(3)
Results:
Treatment
significantly
improved
DOX-caused
altered
cardiac
damage
markers
(LDH,
CK-MB,
cTn-T),
marked
improvement
histopathological
features
accompanied
this.
downregulated
expression
Nrf2/HO-1
signaling
pathways,
reversed
effect.
Consistently,
caspase-3,
apoptotic-related
marker,
dityrosine
suppressed,
while
Nrf2
HO-1
expressions
elevated
tissues
DOX-treated
after
treatment
CGA.
Furthermore,
recovery
confirmed
by
downregulation
8-OHdG
(DT)
immunohistochemical
findings.
(4)
Conclusions:
demonstrated
considerable
effect
against
One
possible
these
protective
upregulation
Nrf2/HO-1-dependent
pathway
DT,
which
may
oxidative
stress
cardiomyocyte
apoptosis.
These
findings
suggest
be
particularly
patients
receiving
DOX-based
chemotherapy.
British Journal of Pharmacology,
Год журнала:
2024,
Номер
181(21), С. 4195 - 4213
Опубликована: Июль 3, 2024
Doxorubicin
is
widely
used
in
the
treatment
of
malignant
tumours,
but
doxorubicin-induced
cardiotoxicity
severely
limits
its
clinical
application.
Spexin
a
neuropeptide
that
acts
as
novel
biomarker
cardiovascular
disease.
However,
effects
spexin
on
unclear.
Biomedicine & Pharmacotherapy,
Год журнала:
2022,
Номер
153, С. 113403 - 113403
Опубликована: Июль 13, 2022
Doxorubicin
(Dox)-induced
cardiotoxicity
(DIC)
seriously
threatens
the
health
of
related
patients.
Studies
have
confirmed
that
14-3-3γ
and
protein
kinase
C
epsilon
(PKCε)
are
endogenous
protective
proteins.
Puerarin
(Pue)
is
a
bioactive
ingredient
isolated
from
root
Pueraria
lobata.
It
possesses
many
pharmacological
properties,
which
been
widely
used
in
treating
adjuvant
therapy
cardiovascular
diseases.
In
study,
we
intended
to
explore
effects
mechanism
Pue
pretreatment
protect
myocardium
against
DIC
injury.
Adult
mice
H9c2
cells
were
pretreated
with
Pue,
injury
model
was
made
Dox.
Results
showed
alleviated
injury,
as
revealed
by
increased
cell
viability,
decreased
LDH
activity
apoptosis,
inhibited
excess
oxidative
stress,
maintained
mitochondrial
function
energy
metabolism,
improved
myocardial
function.
Furthermore,
upregulated
expression,
interacted
PKCε,
phosphorylated
impelled
migration
mitochondria,
activated
adaptive
autophagy,
protected
myocardium.
However,
pAD/14-3-3γ-shRNA
or
εV1-2
(a
PKCε
inhibitor)
3-methyladenine
(an
autophagy
could
weaken
above
pretreatment.
Together,
activate
14-3-3γ/PKCε
pathway
Cancers,
Год журнала:
2023,
Номер
15(7), С. 1963 - 1963
Опубликована: Март 24, 2023
The
survival
rate
for
pediatric
cancers
has
remarkably
improved
in
recent
years.
Conventional
chemotherapy
plays
a
crucial
role
treating
cancers,
especially
low-
and
middle-income
countries
where
access
to
advanced
treatments
may
be
limited.
Food
Drug
Administration
(FDA)
approved
drugs
that
can
used
children
have
expanded,
but
patients
still
face
numerous
side
effects
from
the
treatment.
In
addition,
multidrug
resistance
(MDR)
continues
pose
major
challenge
improving
rates
significant
number
of
patients.
This
review
focuses
on
severe
chemotherapy,
including
doxorubicin-induced
cardiotoxicity
(DIC)
vincristine-induced
peripheral
neuropathy
(VIPN).
We
also
delve
into
mechanisms
MDR
improve
reduce
toxicity
Additionally,
various
drug
transporters
found
common
types
tumors,
which
could
offer
different
therapeutic
options.
