Free Radical Biology and Medicine,
Journal Year:
2024,
Volume and Issue:
224, P. 39 - 49
Published: Aug. 10, 2024
The
pathogenesis
of
intervertebral
disc
degeneration
(IVDD)
involves
complex
signaling
networks
and
various
effector
molecules,
our
understanding
the
IVDD
is
limited.
Hypoxia
inducible
factor-1α
(HIF-1α)
closely
related
to
IVDD,
there
excessive
oxidative
stress
concurrent
with
IVDD.
In
this
study,
we
found
that
HIF-1α
could
protect
nucleus
pulposus
cells
from
by
reversing
imbalance
between
oxidants
antioxidants
thus
mitigating
stress-induced
mitochondrial
impairment.
With
further
exploration,
pyruvate
dehydrogenase
kinase
1
(PDK-1)
was
involved
in
protective
effect
on
under
stress.
We
suggested
preserve
integrity
activate
glycolysis
via
PDK-1,
addition
DCA,
a
PDK-1
inhibitor,
blunt
HIF-1α.
addition,
HIF-1α/PDK-1
regulatory
axis
also
confirmed
vivo
through
knockout
mice
model.
Therefore,
propose
protects
maintaining
enriching
insight
into
mechanism
against
providing
novel
therapeutic
target
for
treatment
Scientific Reports,
Journal Year:
2023,
Volume and Issue:
13(1)
Published: Aug. 1, 2023
Abstract
The
present
work
examined
the
effect
of
oral
administration
rutin
and
its
combination
with
metformin,
an
antidiabetic
drug
on
blood
glucose,
total
cholesterol
triglycerides
level
vascular
function
in
streptozotocin
(STZ)
-induced
diabetic
rats.
Male
Sprague
Dawley
rats
were
rendered
by
a
single
intraperitoneal
injection
STZ
(50
mg/kg).
Rutin
metformin
orally
administered
to
at
dose
100
mg/kg
300
body
weight/day,
respectively,
for
4
weeks.
Plasma
analysis
was
conducted
determine
changes
plasma
glucose
lipid
levels.
Rat
aortic
ring
reactivity
response
endothelium-dependent
(acetylcholine,
ACh)
endothelium-independent
(sodium
nitroprusside,
SNP)
relaxants,
α1-adrenergic
agonist
phenylephrine
(PE)
recorded.
Histology
pancreas,
liver
kidney
evaluated.
In
results,
alone
has
led
significant
improvements
triglyceride
levels
compared
group.
Diabetic
rings
showed
significantly
greater
contraction
PE,
less
relaxation
ACh
SNP.
Treatment
reduced
PE-induced
increased
ACh-induced
SNP-induced
diabetes
when
or
alone.
Significant
histological
seen
therapy.
conclusion,
therapy
most
potentiality
restoring
as
well
function.
Free Radical Biology and Medicine,
Journal Year:
2024,
Volume and Issue:
224, P. 39 - 49
Published: Aug. 10, 2024
The
pathogenesis
of
intervertebral
disc
degeneration
(IVDD)
involves
complex
signaling
networks
and
various
effector
molecules,
our
understanding
the
IVDD
is
limited.
Hypoxia
inducible
factor-1α
(HIF-1α)
closely
related
to
IVDD,
there
excessive
oxidative
stress
concurrent
with
IVDD.
In
this
study,
we
found
that
HIF-1α
could
protect
nucleus
pulposus
cells
from
by
reversing
imbalance
between
oxidants
antioxidants
thus
mitigating
stress-induced
mitochondrial
impairment.
With
further
exploration,
pyruvate
dehydrogenase
kinase
1
(PDK-1)
was
involved
in
protective
effect
on
under
stress.
We
suggested
preserve
integrity
activate
glycolysis
via
PDK-1,
addition
DCA,
a
PDK-1
inhibitor,
blunt
HIF-1α.
addition,
HIF-1α/PDK-1
regulatory
axis
also
confirmed
vivo
through
knockout
mice
model.
Therefore,
propose
protects
maintaining
enriching
insight
into
mechanism
against
providing
novel
therapeutic
target
for
treatment
