Metformin ameliorates Gestational Diabetes Mellitus via inhibiting ferroptosis of trophoblasts through the Nrf2/HO-1 signaling pathway
Lingya Fang,
Sha Lu,
Liuyuan Fang
и другие.
Free Radical Research,
Год журнала:
2025,
Номер
unknown, С. 1 - 17
Опубликована: Фев. 17, 2025
Both
mothers
and
infants
experience
oxidative
stress
due
to
gestational
diabetes
mellitus
(GDM),
which
is
strongly
associated
with
adverse
pregnancy
outcomes.
Ferroptosis,
a
novel
form
of
programmed
cell
death
characterized
by
iron-dependent
lipid
peroxidation,
believed
play
critical
role
in
the
pathogenesis
progression
GDM.
Metformin
(MET)
has
shown
potential
alleviating
stress;
however,
research
on
its
specific
mechanisms
action
GDM
remains
limited.
We
collected
placental
tissues
from
patients
healthy
controls
established
an
vitro
model.
measured
markers
ferroptosis
including
malondialdehyde
(MDA),
glutathione
(GSH),
peroxidase
4
(GPX4)
activity.
Additionally,
we
evaluated
reactive
oxygen
species
(ROS)
levels,
apoptosis,
viability,
migration
Our
findings
revealed
significant
changes
group
compared
controls,
increased
MDA
GSSG
decreased
GSH
reduced
expression
GPX4
protein
placenta.
High-glucose
(HG)
conditions
were
reduce
trophoblast
viability
migration,
accompanied
elevated
ROS
as
well
GSH,
GPX4,
Nrf2,
HO-1
proteins.
Importantly,
treatment
MET
reversed
these
effects,
similar
deferoxamine
mesylate
(DFOM),
known
inhibitor.
These
results
confirm
occurrence
placentas
demonstrate
that
mitigates
high-glucose-induced
trophoblasts
through
Nrf2/HO-1
signaling
pathway.
This
study
provides
insights
into
protective
MET,
offering
therapeutic
strategies
for
management.
Язык: Английский
Mitochondrial Oxidative Phosphorylation Alterations in Placental Tissues from Early- and Late-Onset Preeclampsia
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(9), С. 3951 - 3951
Опубликована: Апрель 22, 2025
Preeclampsia
(PE),
a
pregnancy
complication
characterized
by
high
blood
pressure
and
organ
damage,
has
been
suggested
to
be
associated
with
mitochondrial
dysfunction,
although
evidence
remains
limited.
This
study
aimed
investigate
the
activity
of
oxidative
phosphorylation
(OXPHOS)
enzymes
expression
related
proteins
in
placental
tissues
from
women
diagnosed
early-onset
preeclampsia
(eoPE,
<34
weeks
gestation),
late-onset
(loPE,
≥34
normotensive
controls.
Placental
samples
were
analyzed
using
immunohistochemistry,
western
blotting,
enzymatic
assays
assess
OXPHOS
complexes.
Complex
I
was
increased
80%
eoPE
56%
loPE,
positive
correlations
between
normalized
complex
expression,
gestational
age
at
delivery
(r
=
0.85,
p
0.01),
birth
weight
0.88,
0.004)
loPE.
Relative
II
loPE
showed
duration
0.76,
0.03)
0.77,
0.03),
while
controls,
correlated
0.64,
0.03).
Additionally,
IV
enzyme
negatively
maternal
−0.69,
The
observed
highlight
metabolism
as
promising
biomarker
for
predicting
disease
progression
guiding
therapeutic
interventions
preeclampsia.
Unraveling
its
precise
role
PE
pathogenesis
is
critical
advancing
diagnostic
precision
improving
maternal-fetal
outcomes.
Язык: Английский