Frontiers in Pharmacology,
Год журнала:
2022,
Номер
13
Опубликована: Ноя. 17, 2022
Acute
kidney
injury
(AKI),
one
of
the
most
prevalent
clinical
diseases
with
a
high
incidence
rate
worldwide,
is
characterized
by
rapid
deterioration
renal
function
and
further
triggers
accumulation
metabolic
waste
toxins,
leading
to
complications
dysfunction
other
organs.
Multiple
pathogenic
factors,
such
as
rhabdomyolysis,
infection,
nephrotoxic
medications,
ischemia-reperfusion
injury,
contribute
onset
progression
AKI.
However,
detailed
mechanism
remains
unclear.
Ferroptosis,
recently
identified
nonapoptotic
cell
death,
iron-dependent
caused
lipid
peroxide
in
cells.
A
variety
studies
have
demonstrated
that
ferroptosis
plays
significant
role
AKI
development,
contrast
forms
apoptosis,
necroptosis,
pyroptosis.
In
this
review,
we
systemically
summarized
definition,
primary
biochemical
mechanisms,
key
regulators
associated
pharmacological
research
progress
We
discussed
its
therapeutic
potential
for
prevention
AKI,
hope
providing
useful
reference
basic
studies.
The American Journal of Chinese Medicine,
Год журнала:
2023,
Номер
51(04), С. 997 - 1018
Опубликована: Янв. 1, 2023
Diabetic
nephropathy
(DN)
is
thought
to
be
the
major
cause
of
end-stage
renal
disease.
Due
its
complicated
pathogenesis
and
low
efficacy
DN
treatment,
a
deep
understanding
new
etiological
factors
may
useful.
Ferroptosis,
nonapoptotic
form
cell
death,
characterized
by
accumulation
iron-dependent
lipid
peroxides
lethal
levels.
Ferroptosis-triggered
tubular
injury
reported
participate
in
development
DN,
blocking
ferroptosis
might
an
effective
strategy
prevent
DN.
Quercetin
(QCT),
natural
flavonoid
that
present
variety
fruits
vegetables,
has
been
ameliorate
However,
underlying
nephroprotective
mechanism
unclear.
Herein,
we
explored
antiferroptosic
effect
QCT
verified
using
mice
high
glucose
(HG)-incubated
epithelial
models.
We
found
HG-induced
abnormal
activation
cells,
treatment
inhibited
downregulating
expression
transferrin
receptor
1
(TFR-1)
upregulating
glutathione
peroxidase
4
(GPX4),
ferritin
heavy
chain
(FTH-1),
cystine/glutamate
reverse
antiporter
solute
carrier
family
7
member
(SLC7A11)
HG-incubated
HK-2
cells.
Subsequently,
both
vitro
vivo
results
confirmed
activated
NFE2-related
factor
2
(Nrf2)/Heme
oxygenase-1(HO-1)
signaling
pathway
increasing
levels
Nrf2
HO-1.
Therefore,
this
study
supports
inhibits
cells
regulating
Nrf2/HO-1
pathway,
providing
novel
insight
into
protective
treatment.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
174, С. 116512 - 116512
Опубликована: Апрель 3, 2024
GPX4
(Glutathione
peroxidase
4)
serves
as
a
crucial
intracellular
regulatory
factor,
participating
in
various
physiological
processes
and
playing
significant
role
maintaining
the
redox
homeostasis
within
body.
Ferroptosis,
form
of
iron-dependent
non-apoptotic
cell
death,
has
gained
considerable
attention
recent
years
due
to
its
involvement
multiple
pathological
processes.
is
closely
associated
with
ferroptosis
functions
primary
inhibitor
this
process.
Together,
contribute
pathophysiology
several
diseases,
including
sepsis,
nervous
system
ischemia
reperfusion
injury,
cardiovascular
cancer.
This
review
comprehensively
explores
roles
impacts
development
progression
these
aim
providing
insights
for
identifying
potential
therapeutic
strategies
future.
Cellular and Molecular Neurobiology,
Год журнала:
2023,
Номер
43(7), С. 3329 - 3341
Опубликована: Июль 17, 2023
Abstract
Ferroptosis
is
a
new
form
of
programmed
cell
death,
which
characterized
by
the
iron-dependent
accumulation
lipid
peroxidation
and
increase
ROS,
resulting
in
oxidative
stress
death.
Iron,
lipid,
multiple
signaling
pathways
precisely
control
occurrence
implementation
ferroptosis.
The
mainly
include
Nrf2/HO-1
pathway,
p62/Keap1/Nrf2
pathway.
Activating
pathway
inhibits
promotes
Furthermore,
some
factors
also
participate
ferroptosis
under
hypoxia,
such
as
HIF-1,
NCOA4,
DMT1.
Meanwhile,
related
with
hypoxia-related
diseases,
MIRI,
cancers,
AKI.
Accordingly,
appears
to
be
therapeutic
target
for
diseases.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Май 23, 2024
Ferroptosis
is
a
non-apoptotic
mode
of
programmed
cell
death
characterized
by
iron
dependence
and
lipid
peroxidation.
Since
the
ferroptosis
was
proposed,
researchers
have
revealed
mechanisms
its
formation
continue
to
explore
effective
inhibitors
in
disease.
Recent
studies
shown
correlation
between
pathological
neurodegenerative
diseases,
as
well
diseases
involving
tissue
or
organ
damage.
Acting
on
ferroptosis-related
targets
may
provide
new
strategies
for
treatment
ferroptosis-mediated
diseases.
This
article
specifically
describes
metabolic
pathways
summarizes
reported
action
natural
synthetic
small
molecule
their
efficacy
The
paper
also
treatments
such
gene
therapy,
nanotechnology,
summarises
challenges
encountered
clinical
translation
inhibitors.
Finally,
relationship
other
modes
discussed,
hopefully
paving
way
future
drug
design
discovery.
Diabetic
kidney
disease
(DKD)
is
a
leading
factor
in
end-stage
renal
disease.
The
complexity
of
its
pathogenesis,
combined
with
the
limited
treatment
efficacy,
necessitates
deeper
insights
into
potential
causes.
Studies
suggest
that
ferroptosis-driven
tubular
damage
contributes
to
DKD's
progression,
making
counteraction
therapeutic
strategy.
Quercetin,
flavonoid
found
numerous
fruits
and
vegetables,
has
demonstrated
DKD
mitigation
mouse
models,
though
protective
mechanism
remains
ambiguous.
In
this
study,
we
delved
quercetin's
anti-ferroptotic
properties,
employing
rat
model
high
glucose
(HG)-treated
epithelial
cell
models.
Our
findings
revealed
HG
prompted
unusual
ferroptosis
activation
cells.
However,
quercetin
counteracted
by
inhibiting
activating
NFE2-related
2
(Nrf2)
expression
both
rats
HG-treated
HK-2
cells,
indicating
role.
Further
experiments,
vivo
vitro,
validated
stimulates
Nrf2.
Thus,
our
research
underscores
modulating
process
via
Nrf2
distinct
model,
offering
fresh
perspective
on
mechanisms.
International Immunopharmacology,
Год журнала:
2024,
Номер
129, С. 111564 - 111564
Опубликована: Фев. 5, 2024
The
pathological
mechanism
of
sepsis-associated
acute
kidney
injury
(SA-AKI)
is
complex
and
involves
tubular
epithelial
cell
(TEC)
death
immune
activation.
However,
the
interaction
between
macrophage-mediated
inflammation
remains
unclear.
In
this
study,
we
uncovered
that
TEC
ferroptosis
was
activated
in
SA-AKI.
Increased
levels
ferroptotic
markers,
including
ferroptosis-related
proteins,
lipid
peroxidation,
malondialdehyde
(MDA),
4-hydroxynonenal
(4-HNE),
reactive
oxygen
species
(ROS),
mitochondrial
damage,
were
observed
tissue
cecum
ligation
puncture
(CLP)
Lipopolysaccharide
(LPS)-induced
SA-AKI
mouse
models,
which
subsequently
suppressed
by
Ferrostatin-1
(Fer-1).
vitro
experiments
showed
Fer-1
inhibits
LPS-induced
Fe2+
accumulation,
cytosolic
ROS
production.
Moreover,
it
found
induced
promoted
macrophage-inducible
C-type
lectin
(Mincle)
its
downstream
expression
M1
polarization,
mediated
release
spliceosome-associated
protein
130
(SAP130),
an
endogenous
ligand
Mincle,
from
TEC.
It
confirmed
supernatant
LPS-stimulated
TECs
Mincle
polarization
macrophages.
Further
revealed
macrophages
aggravated
ferroptosis,
offset
neutralizing
SAP130
or
inhibiting
expression.
addition,
circulatory
blunted
expression,
as
well
macrophage
infiltration
mice.
conclusion,
triggering
Mincle/syk/NF-κB
signaling,
macrophages,
turn,
ferroptosis.
