Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in mice
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 22, 2025
Background
Epilepsy
is
a
neurological
disorder
characterized
by
recurrent
seizures
due
to
abnormal
electrical
activity
in
the
brain.
Pirfenidone,
an
antifibrotic
drug,
has
shown
anti-inflammatory
and
antioxidant
properties
various
disease
models,
including
conditions.
However,
its
potential
anticonvulsant
effects
have
not
been
thoroughly
explored.
This
study
aims
evaluate
of
pirfenidone
pentylenetetrazol-induced
kindling
model
epilepsy,
focusing
on
effect
seizure
activity,
cognition,
profiles,
inflammatory
markers,
neurotransmitter
balance,
liver
enzyme
levels,
histopathological
changes.
Methods
Healthy
male
Swiss
albino
mice
were
subjected
acute
Increasing
Current
Electroshock
test
chronic
pentylenetetrazol-kindling
model.
Pirfenidone
was
administered
at
doses
100,
200,
300
mg/kg,
orally,
with
sodium
valproate
as
standard
drug.
Seizure
severity
cognitive
function
assessed
model,
along
biochemical
assays
that
evaluated
enzymes,
levels.
Histopathological
changes
also
hippocampus
cortex
experimental
mice.
Results
200
mg/kg
significantly
increased
Threshold
test,
indicating
protective
against
seizures.
In
delayed
onset
reduced
severity,
dose
showing
strongest
impact.
demonstrated
significant
improvements
function,
evidenced
enhanced
performance
passive
avoidance
elevated
plus
maze
tests.
Antioxidant
profiles
showed
levels
superoxide
dismutase,
catalase,
glutathione,
corresponding
reduction
malondialdehyde
acetylcholinesterase
pro-inflammatory
cytokines
interleukin-6,
interleukin-1β,
transforming
growth
factor-β,
tumor
necrosis
factor-
α,
high-mobility
group
box-1,
toll-like
receptor-4,
gamma-aminobutyric
acid,
decreased
glutamate
modulated
aspartate
aminotransferase
alanine
analysis
revealed
ameliorated
cellular
disintegration
neuronal
damage
cortex.
Conclusion
shows
anticonvulsant,
anti-inflammatory,
hepatoprotective,
neuroprotective
agent,
additional
benefits
improving
cognition
oxidative
stress
epilepsy
treatment.
Further
studies
are
required
explore
long-term
safety
efficacy.
Язык: Английский
Sodium butyrate ameliorates mitochondrial oxidative stress and alterations in membrane-bound enzyme activities in pentylenetetrazole-induced kindling rat model
Metabolic Brain Disease,
Год журнала:
2025,
Номер
40(2)
Опубликована: Фев. 6, 2025
Язык: Английский
Brain targeted lactoferrin coated lipid nanocapsules for the combined effects of apocynin and lavender essential oil in PTZ induced seizures
Drug Delivery and Translational Research,
Год журнала:
2024,
Номер
15(2), С. 534 - 555
Опубликована: Май 31, 2024
Apocynin
(APO)
is
a
plant
derived
antioxidant
exerting
specific
NADPH
oxidase
inhibitory
action
substantiating
its
neuroprotective
effects
in
various
CNS
disorders,
including
epilepsy.
Due
to
rapid
elimination
and
poor
bioavailability,
treatment
with
APO
challenging.
Correspondingly,
novel
APO-loaded
lipid
nanocapsules
(APO-LNC)
were
formulated
coated
lactoferrin
(LF-APO-LNC)
improve
br
ain
targetability
prolong
residence
time.
Lavender
oil
(LAV)
was
incorporated
into
LNC
as
bioactive
ingredient
act
synergistically
alleviating
pentylenetetrazol
(PTZ)-induced
seizures.
The
optimized
LF-APO-LAV/LNC
showed
particle
size
59.7
±
4.5
nm
narrow
distribution
6.07
1.6mV
zeta
potential)
high
entrapment
efficiency
92
2.4%
sustained
release
(35%
72
h).
Following
subcutaneous
administration,
brought
about
⁓twofold
increase
plasma
AUC
MRT
compared
APO.
A
Log
BB
value
of
0.2
0.14
at
90
min
reflects
increased
brain
accumulation.
In
PTZ-induced
seizures
rat
model,
Modified
Racine
score
0.67
0.47
significant
latency
decrease
duration.
Moreover,
oxidant/antioxidant
capacity
inflammatory
markers
levels
tissue
significantly
improved.
Histopathological
immunohistochemical
assessment
sections
further
supported
these
findings.
results
suggest
APO/LAV
combination
LF-coated
promising
approach
counteract
Язык: Английский
Effect of solid lipid nanoparticles loaded with valproate and metformin on pentylenetetrazole-induced epilepsy in rats
R. Abinaya,
V. K. Kalaichelvan,
K. Gopalasatheeskumar
и другие.
Naunyn-Schmiedeberg s Archives of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 5, 2025
Язык: Английский
Vitamin E-Valproate Co-Therapy Attenuated oxidative stress, neuroinflammation, related cognitive deficits and neuronal damage in Cypermethrin exacerbated seizure
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 14, 2025
Abstract
Background:
Epilepsy,
characterized
by
recurrent
seizures
and
associated
cognitive
impairments,
is
often
exacerbated
environmental
neurotoxins
such
as
Cypermethrin.
This
study
investigates
the
effects
of
Cypermethrin
(CPM)
on
Pentylenetetrazole
(PTZ)-induced
potential
neuroprotective
properties
Vitamin
E
(VIT
E)
valproate
(VAP),
both
alone
in
combination.
Methods:
Behavioral
tests,
biochemical
assays,
immunohistochemical
analyses
were
conducted
to
assess
seizure
severity,
performance,
neuronal
integrity,
markers
neuroinflammation
oxidative
stress.
Results:
PTZ-induced
significantly
increased
severity
impaired
performance
T-maze,
Y-maze,
Morris’
water
maze
with
these
deficits
being
CPM.
Immunohistochemical
staining
revealed
substantial
interneuron
loss
hippocampus,
accompanied
heightened
microglial
activation.
Biochemical
showed
elevated
levels
pro-inflammatory
cytokines
(TNF-α)
stress
(MDA),
alongside
reduced
antioxidant
enzyme
activity
(SOD).
Therapeutic
intervention
VAP
or
VIT
mitigated
varying
degrees.
Combination
therapy
was
particularly
effective,
demonstrating
significant
improvements
scores,
reductions
markers.
These
findings
underscore
synergistic
benefits
combining
managing
neuropathologies.
Conclusion:
This
highlights
exacerbating
toxins
seizure-related
impairments
while
providing
evidence
for
antioxidant-based
combination
therapies
a
promising
approach
mitigate
effects.
Язык: Английский
Scorpion venom heat-resistant synthesized peptide ameliorates epileptic seizures and imparts neuroprotection in rats mediated by NMDA receptors
European Journal of Pharmacology,
Год журнала:
2024,
Номер
978, С. 176704 - 176704
Опубликована: Июнь 1, 2024
Язык: Английский
Diverse perspectives in zebrafish seizure models: An exploration of chemical inducers
World Journal of Advanced Research and Reviews,
Год журнала:
2024,
Номер
21(3), С. 865 - 877
Опубликована: Март 12, 2024
Numerous
studies
have
investigated
seizures
in
zebrafish,
employing
diverse
methods
to
induce
and
observe
epilepsy.
Chemical
inducers
become
indispensable
tools
for
precisely
manipulating
neural
activity
controlled
experiments.
This
research
is
dedicated
a
meticulous
comparison
analysis
of
various
seizure-inducing
chemicals
zebrafish.
The
selected
chemical
include
pentylenetetrazole
(PTZ),
kainic
acid
(KA),
picrotoxin
(PTX),
pilocarpine,
other
substances.
primary
mechanism
these
involves
altering
neurotransmitter
receptors,
particularly
GABA
glutamate,
at
inhibitory
or
excitatory
synapses.
alteration
creates
an
imbalance
between
signals
the
brain,
contributing
epileptogenesis.
resulting
hyperactivity
zebrafish
brain
disrupts
metabolism,
elevates
reactive
oxygen
species
(ROS),
causes
neuronal
damage.
induction
offers
valuable
insights
into
neurological
enabling
observation
behaviors
such
as
whole-body
contractions,
loss
posture,
freezing.
Various
parameters
can
be
adjusted
examine
effects
on
development
replicate
types
seizures,
status
epilepticus
temporal
lobe
Despite
array
options
available,
many
remain
underutilized
studies.
To
ensure
successful
models,
monitoring
gene
expression
markers
c-fos,
which
represents
activity,
becomes
crucial.
Additionally,
scoring
system
employed
analyze
seizure
severity
identify
treatment
efficacy.
existing
gaps
utilizing
present
great
opportunities
future
model
development.
chemically-induced
pivotal
unraveling
mechanisms,
significantly
advancements
research.
Язык: Английский
Studying the Anti-Anxiety and Anti-Convulsant Impacts of Royal Jelly in Mice
International Journal of Pharmaceutical and Phytopharmacological Research,
Год журнала:
2024,
Номер
14(5), С. 25 - 30
Опубликована: Янв. 1, 2024
Язык: Английский
Elucidating the Biochemical Role of Novel Enzyme Targets in Neurodegenerative Disorders
Abdullah Abbas Hamzah Al-Rubaye
Research Square (Research Square),
Год журнала:
2023,
Номер
unknown
Опубликована: Окт. 19, 2023
Abstract
Introduction:
Neurodegenerative
disorders,
characterized
by
progressive
neuronal
loss,
remain
a
significant
clinical
challenge
due
to
their
multifactorial
etiology.
While
numerous
enzymes
have
been
implicated
in
pathogenesis,
there
remains
knowledge
gap
regarding
the
precise
biochemical
roles
of
several
novel
enzyme
targets.
Methods:
This
study
encompassed
multi-pronged
approach,
involving
patient-derived
samples
from
Alzheimer's
and
Parkinson's
cases
(n=156),
an
ALS
mouse
model
(n=50),
CRISPR-Cas9
edited
Huntington's
Disease
zebrafish
(n=100).
Enzyme
activity
assays,
localization
microscopy,
interaction
pathway
analyses
were
conducted.
Results:
Elevated
Aminotransferases
was
observed
78%
compared
controls
(p<0.05).
The
revealed
30%
reduction
motor
neuron
counts
tandem
with
altered
(p<0.01).
successfully
displayed
genetic
markers
post-CRISPR
editing,
indicating
95%
editing
efficiency.
Furthermore,
interactions
between
established
neurodegenerative
pathways
identified.
Conclusion:
Mine
findings
highlight
pivotal
role
targets
offering
potential
avenues
for
early
detection
therapeutic
interventions.
intricate
interplay
these
known
disease
underscores
need
integrated
approach
understand
mechanisms
holistically.
Язык: Английский