Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Dec. 5, 2024
Lead
is
a
pervasive
environmental
contaminant
with
significant
health
risks,
particularly
to
children.
It
known
for
its
neurotoxic
and
immunotoxic
effects,
causing
developmental,
cognitive,
behavioral
impairments.
Despite
extensive
research,
the
mechanisms
of
lead
toxicity
remain
unclear.
Cytokines,
which
are
critical
in
immune
response
inflammation,
have
emerged
as
potential
biomarkers
toxicity.
The
recent
Centers
Disease
Control
Prevention
(CDC)
update
blood
reference
value
(BLRV)
3.5
µg/dL
emphasizes
need
explore
novel
mechanisms.
study
involved
100
healthy
children
aged
1
5
years,
divided
into
two
groups
based
on
BLRV:
elevated
(≥
µg/dL)
low
(<
µg/dL).
research
consisted
phases:
discovery
validation.
Plasma
samples
were
analyzed
using
RayBio®
Human
Cytokine
Antibody
Arrays
Enzyme-linked
immunosorbent
assay
(ELISA)
cytokine
levels.
Ethical
approval
was
obtained,
statistical
analyses
included
t-tests,
chi-squared
tests,
pearson
correlations,
multivariate
logistic
regression.
Protein-protein
interaction
(PPI),
Gene
Ontology
(GO)
enrichment,
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
pathway
conducted
roles
differentially
expressed
proteins
(DEPs).
No
differences
age,
gender,
or
BMI
between
groups,
but
BLRV
levels
significantly
higher
group
compared
group.
In
phase,
changes
expression
identified,
including
increased
IL-6,
IL-8,
IL-17,
decreased
BDNF,
BMP-4,
IGF-1,
IL-7,
IL-10,
Leptin.
These
findings
validated
second
phase
ELISA.
Significant
positive
correlations
found
IL-17.
Negative
observed
Multivariate
regression
confirmed
that
affects
these
PPI
networks
revealed
DEPs
had
strong
interactions
multiple
proteins,
indicating
their
central
role
GO
KEGG
highlighted
pathways
related
neurotoxicity
inflammatory
responses,
"negative
regulation
myotube
differentiation,"
"neurotrophin
signaling
pathway,"
"alcoholism."
This
provides
insights
cytokines
offers
comprehensive
analysis
involved.
underscore
importance
early
detection
intervention
updated
thresholds.
Toxicology,
Journal Year:
2024,
Volume and Issue:
503, P. 153771 - 153771
Published: March 1, 2024
Lead
(Pb2+)
is
a
hazardous
heavy
metal
that
pervasive
in
the
human
environment
as
result
of
anthropogenic
activity,
and
poses
serious
health
risks,
particularly
children.
Due
to
its
innumerable
unique
physical
chemical
properties,
it
has
various
applications;
therefore,
become
common
environmental
pollutant.
may
cause
oxidative
stress,
accumulating
evidence
indicates
stress
influences
pathophysiology
lead
poisoning,
also
called
plumbism.
The
immune
system
continually
exposed
pathogens
xenobiotics,
including
metals
such
lead,
appears
be
one
most
vulnerable
targets.
After
being
cells
are
subjected
reactive
oxygen
species
(ROS)
production.
When
generation
consumption
ROS
out
equilibrium,
cell
structures,
phospholipids
disrupted
leading
lipid
peroxidation.
Various
inflammatory
signalling
pathways
activated
consequence,
along
with
reduced
disease
resistance,
inflammation,
autoimmunity,
sensitization
disruption
cell-mediated
humoral
systems.
negatively
affects
metabolism
cytokines,
interleukins
IL-2,
IL-1b,
IL-6,
IL-4,
IL-8,
tumor
necrosis
factor-alpha
(TNF-α),
interferon-gamma
(IFN),
well
expression
functioning
enzymes
cyclooxygenases.
However,
toxicity
depends
on
kind
dosage,
route
entry,
exposure
period,
age,
host
genetic
predisposition.
Environment International,
Journal Year:
2024,
Volume and Issue:
184, P. 108479 - 108479
Published: Feb. 1, 2024
Lead
is
an
environmentally
widespread
neurotoxic
pollutant.
Although
the
neurotoxicity
of
lead
has
been
found
to
be
closely
associated
with
metabolic
disorders,
effects
short-chain
fatty
acids
on
and
its
mechanisms
have
not
yet
explored.
In
this
study,
results
open
field
tests
Morris
water
maze
demonstrated
that
chronic
exposure
caused
learning
memory
deficits
anxiety-like
symptoms
in
mice.
The
serum
butyric
acid
content
lead-treated
mice
decreased
a
dose-dependent
manner,
oral
administration
butyrate
significantly
improved
cognitive
impairment
anxiety
lead-exposed
Moreover,
alleviated
neuroinflammation
by
inhibiting
STAT3
signaling
microglia.
Butyrate
also
promoted
expression
acetyl-CoA
synthetase
ACSS2
hippocampal
neurons,
thereby
increasing
restoring
both
histone
H3K9ac
downstream
BDNF.
We
median
concentration
high-lead
humans
was
remarkably
lower
than
low-lead
(45.16
μg/L
vs.
60.92
μg/L,
P
<
0.01),
mediated
relationship
Montreal
assessment
scores,
contribution
rate
27.57%.
conclusion,
our
suggest
supplementation
possible
therapeutic
strategy
for
lead-induced
neurotoxicity.
Environment International,
Journal Year:
2023,
Volume and Issue:
181, P. 108253 - 108253
Published: Oct. 13, 2023
Lead
is
a
common
environmental
heavy
metal
contaminant.
Humans
are
highly
susceptible
to
lead
accumulation
in
the
body,
which
causes
nervous
system
damage
and
leads
variety
of
diseases,
such
as
Alzheimer's
disease,
Parkinson's
autism
spectrum
disorder.
Recent
research
has
focused
on
mechanisms
lead-induced
neurotoxicity
at
multiple
levels,
including
DNA
methylation,
histone
modifications,
non-coding
RNAs,
involved
various
diseases.
We
reviewed
latest
articles
summarised
emerging
roles
modification,
RNAs
neurotoxicity.
Our
summary
provides
theoretical
basis
directions
for
future
prevention,
diagnosis,
treatment
neurological
Ecotoxicology and Environmental Safety,
Journal Year:
2024,
Volume and Issue:
271, P. 115991 - 115991
Published: Jan. 17, 2024
Heavy
metal
toxicity
is
a
significant
global
health
concern,
with
particular
attention
given
to
lead
(Pb)
exposure
due
its
adverse
effects
on
cognitive
development,
especially
in
children
exposed
low
concentrations.
While
Pb
neurotoxicity
has
been
extensively
studied,
the
analysis
and
molecular
mechanisms
underlying
transgenerational
of
exposure-induced
remain
poorly
understood.
In
this
study,
we
utilized
Drosophila,
powerful
developmental
animal
model,
investigate
phenomenon.
Our
findings
demonstrated
that
during
stage
had
profound
effect
neurodevelopment
F0
fruit
flies.
Specifically,
observed
loss
correlation
between
terminal
motor
area
muscle
fiber
area,
along
an
increased
frequency
β-lobe
midline
crossing
phenotype
mushroom
bodies.
Western
blot
indicated
altered
expression
levels
synaptic
vesicle
proteins,
decrease
Synapsin
(SYN)
increase
Bruchpilot
(BRP)
expression,
suggesting
changes
release
sites.
These
were
corroborated
by
electrophysiological
data,
showing
amplitude
evoked
excitatory
junctional
potential
(EJP)
spontaneous
(mEJP)
following
exposure.
Importantly,
our
results
further
confirmed
resulting
from
grandparental
exhibited
effect.
The
F3
offspring
displayed
neurodevelopmental
defects,
function
abnormalities,
repetitive
behavior
despite
lacking
direct
MeDIP-seq
revealed
alterations
DNA
methylation
several
associated
genes
(eagle,
happyhour,
neuroglian,
bazooka,
spinophilin)
Pb.
suggest
modifications
may
underlie
inheritance
acquired
phenotypic
traits
environmental
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(7), P. 6575 - 6575
Published: March 31, 2023
Autism
spectrum
disorders
(ASD)
are
neurobehavioral
disabilities
characterized
by
impaired
social
interactions,
poor
communication
skills,
and
restrictive/repetitive
behaviors.
Cadmium
is
a
common
heavy
metal
implicated
in
ASD.
In
this
study,
we
investigated
the
effects
of
Cd
exposure
on
BTBR
T+
Itpr3tf/J
(BTBR)
mice,
an
ASD
model.
We
looked
for
changes
repetitive
behaviors
sociability
through
experiments.
also
explored
molecular
mechanisms
underlying
exposure,
focusing
proinflammatory
cytokines
pathways.
Flow
cytometry
measured
IL-17A-,
IL-17F-,
IL-21-,
TNF-α-,
STAT3-,
RORγt-expressing
CD4+
T
cells
from
spleens
experimental
mice.
then
used
RT-PCR
to
analyze
IL-17A,
IL-17F,
IL-21,
TNF-α,
STAT3,
RORγ
mRNA
expression
brain.
The
results
behavioral
experiments
showed
that
significantly
increased
self-grooming
marble-burying
mice
while
decreasing
interactions.
number
CD4+IL-17A+,
CD4+IL-17F+,
CD4+IL-21+,
CD4+TNF-α+,
CD4+STAT3+,
CD4+RORγt+
cells,
upregulating
six
molecules
Overall,
our
suggest
oral
aggravates
immune
abnormalities
animal
These
findings
have
important
implications
etiology
provide
further
evidence
metals
contributing
neurodevelopmental
effects.