Critical Reviews in Toxicology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 55
Published: Feb. 21, 2025
Acetaminophen
[paracetamol;
N-acetyl-para-aminophenol
(APAP)]
is
an
antipyretic/analgesic
commonly
used
in
the
treatment
of
fever
and
mild
to
moderate
pain,
headache,
myalgia,
dysmenorrhea.
Recent
literature
has
questioned
safety
acetaminophen
use
during
pregnancy,
with
emphasis
on
whether
exposure
developing
nervous
system
results
behavioral
changes
consistent
autism
spectrum
disorder
(ASD),
attention-deficit/hyperactivity
(ADHD),
and/or
other
cognitive
deficits
offspring.
No
previous
review
a
fully
detailed,
quantitative
weight-of-evidence
(QWoE)
approach
critically
examine
preclinical
data
regards
potential
developmental
neurotoxicity
(DNT).
Following
regulatory
guidance,
QWoE
framework
using
prespecified
scoring
criteria
was
developed
approaches
characterize
adverse
DNT
outcomes
considerations
for
biological
relevance
response
(outcome
score)
strength
methods
study
design
(methods
score).
Considerations
score
included
(1)
experimental
design,
(2)
details/reliability
measurement(s),
(3)
transparency,
(4)
translational/methodological
relevance.
outcome
response-related
statistical
significance,
dose-response,
relevance/reliability/magnitude,
plausibility,
(5)
translational
relevance,
including
consideration
systemic
toxicity/hepatotoxicity
therapeutic
non-systemically
toxic
doses
durations
use.
Application
this
34
vivo
studies
identified
that
assess
resulted
188
entries
documented
across
11
endpoints:
social
behavior,
stereotypic
rigidity,
attention/impulsivity,
hyperactivity,
anxiety-like
sensorimotor
function,
spatial
learning/memory,
nonspatial
neuroanatomy,
neurotransmission.
For
each
endpoint,
mean
were
calculated
total
segregated
by
sex
assist
determining
quality
adversity.
Informed
all
entries,
analysis
demonstrated
showing
no
evidence
male
female
rodents
following
at
nonsystemically
doses.
Although
some
endpoints
(behavioral
neurotransmission)
generally
displayed
more
limited
dataset
relatively
lower
quality,
similar
conclusions
drawn
based
indicating
lack
reliability
reported
effects.
Overall,
demonstrates
effects
structure
function
system,
neuroanatomical,
neurotransmission,
endpoints.
Advanced Science,
Journal Year:
2023,
Volume and Issue:
10(16)
Published: April 10, 2023
Acetaminophen
(APAP)
overdose
is
a
leading
cause
of
drug-induced
liver
injury
and
acute
failure,
while
the
detection,
prognosis
prediction,
therapy
for
APAP-induced
(AILI)
remain
improved.
Here,
it
determined
that
temporal
pattern
circulating
cell-free
DNA
(cfDNA)
strongly
associated
with
damage
inflammation
parameters
in
AILI.
CfDNA
comparable
to
alanine
aminotransferase
(ALT)
predicting
mortality
outperformed
ALT
when
combined
The
depletion
cfDNA
or
neutrophils
alleviates
damage,
addition
adoptive
transfer
exacerbates
damage.
combination
DNase
I
N-acetylcysteine
attenuates
AILI
significantly.
This
study
establishes
mechanistic
biomarker
predict
mice.
scavenging
reducing
oxidative
provides
promising
treatment
Aging Cell,
Journal Year:
2024,
Volume and Issue:
23(3)
Published: Jan. 5, 2024
Abstract
Recent
advances
in
microphysiological
systems
(MPS),
also
known
as
organs‐on‐a‐chip
(OoC),
enable
the
recapitulation
of
more
complex
organ
and
tissue
functions
on
a
smaller
scale
vitro.
MPS
therefore
provide
potential
to
better
understand
human
diseases
physiology.
To
date,
numerous
platforms
have
been
developed
for
various
tissues
organs,
including
heart,
liver,
kidney,
blood
vessels,
muscle,
adipose
tissue.
However,
only
few
studies
explored
using
unravel
effects
aging
physiology
pathogenesis
age‐related
diseases.
Age
is
one
risk
factors
many
diseases,
enormous
interest
has
devoted
research.
As
such,
model
could
predictive
tool
molecular
cellular
mechanisms
underlying
These
models
can
be
used
evaluate
preclinical
drugs
translate
them
into
clinical
settings.
Here,
we
review
application
First,
offer
an
overview
molecular,
cellular,
physiological
changes
with
age
several
or
organs.
Next,
discuss
previous
current
state
studying
conditions.
Lastly,
address
limitations
present
future
directions
Cell Biology and Toxicology,
Journal Year:
2024,
Volume and Issue:
40(1)
Published: July 15, 2024
Drug-induced
organic
damage
encompasses
various
intricate
mechanisms,
wherein
HMGB1,
a
non-histone
chromosome-binding
protein,
assumes
significant
role
as
pivotal
hub
gene.
The
regulatory
functions
of
HMGB1
within
the
nucleus
and
extracellular
milieu
are
interlinked.
exerts
crucial
influence
on
key
biological
processes
including
cell
survival,
inflammatory
regulation,
immune
response.
can
be
released
extracellularly
from
during
these
processes,
where
it
pro-inflammation
cytokine.
interacts
with
multiple
membrane
receptors,
primarily
Toll-like
receptors
(TLRs)
receptor
for
advanced
glycation
end
products
(RAGE),
to
stimulate
cells
trigger
excessive
or
uncontrolled
release
leads
heightened
responses
cellular
demise,
instigating
exacerbating
inflammation
demise
in
different
diseases.
Therefore,
thorough
review
significance
drug-induced
is
highly
important
advancement
pharmaceuticals,
ensuring
their
effectiveness
safety
treating
well
immune-related
In
this
review,
we
initially
outline
characteristics
emphasizing
relevance
disease
pathology.
Then,
comprehensively
summarize
prospect
promising
therapeutic
target
toxicity.
Lastly,
discuss
major
challenges
propose
potential
avenues
advancing
development
HMGB1-based
therapeutics.
Biomaterials Science,
Journal Year:
2023,
Volume and Issue:
11(7), P. 2348 - 2358
Published: Jan. 1, 2023
As
one
of
the
leading
cases
acute
liver
failure
triggered
by
excessive
Acetaminophen
(APAP),
breakdown
antioxidant
system,
inflammatory
response,
and
inescapable
apoptosis
following
overaccumulation
reactive
oxygen
species
(ROS)
play
crucial
roles
in
mechanisms
APAP-induced
injury
(AILI).
Therefore,
cutting
off
ROS
overproduction
at
source
is
considered
promising.
Here,
manganese
Prussian
blue
nanozymes
(MPBZs)
with
superior
enzyme-like
activity
are
prepared
as
an
effective
strategy
for
hepatocyte
protection,
which
MPBZs
accumulated
show
anti-oxidation
properties
scavenging
superfluous
ROS.
Importantly,
addition
to
alleviating
oxidative
stress,
bioactive
abundant
variable
valence
states
a
natural
enzymes
mediated
responses
multi-biological
signaling
pathways
vitro
vivo,
including
Nrf2-Keap1,
NF-κB,
mitochondrial-induced
pathways,
enhancing
tolerance
imminent
AILI.
Taking
nanomedicine,
hepatology,
catalytic
chemistry
into
consideration,
revealed
performance
AILI
prevention
suggests
that
MPBZ-based
nano-detoxification
therapy
may
offer
alternative
against
Acta Pharmaceutica Sinica B,
Journal Year:
2023,
Volume and Issue:
13(4), P. 1616 - 1630
Published: Jan. 29, 2023
Acetaminophen
(APAP)
overdose
is
a
major
cause
of
liver
injury.
Neural
precursor
cell
expressed
developmentally
downregulated
4-1
(NEDD4-1)
an
E3
ubiquitin
ligase
that
has
been
implicated
in
the
pathogenesis
numerous
diseases;
however,
its
role
APAP-induced
injury
(AILI)
unclear.
Thus,
this
study
aimed
to
investigate
NEDD4-1
AILI.
We
found
was
dramatically
response
APAP
treatment
mouse
livers
and
isolated
hepatocytes.
Hepatocyte-specific
knockout
exacerbated
mitochondrial
damage
resultant
hepatocyte
necrosis
injury,
while
hepatocyte-specific
overexpression
mitigated
these
pathological
events
both
vivo
vitro.
Additionally,
deficiency
led
marked
accumulation
voltage-dependent
anion
channel
1
(VDAC1)
increased
VDAC1
oligomerization.
Furthermore,
knockdown
alleviated
AILI
weakened
exacerbation
caused
by
deficiency.
Mechanistically,
interact
with
PPTY
motif
through
WW
domain
regulate
K48-linked
ubiquitination
degradation
VDAC1.
Our
present
indicates
suppressor
functions
regulating
