Chemical Research in Toxicology,
Год журнала:
2024,
Номер
37(9), С. 1549 - 1561
Опубликована: Авг. 29, 2024
Emerging
environmental
contaminants,
organophosphate
flame
retardants
(OPFRs),
pose
significant
threats
to
ecosystems
and
human
health.
Despite
numerous
studies
reporting
the
toxic
effects
of
OPFRs,
research
on
their
epigenetic
alterations
remains
limited.
In
this
study,
we
investigated
exposure
2-ethylhexyl
diphenyl
phosphate
(EHDPP),
tricresyl
(TMPP),
triphenyl
(TPHP)
DNA
methylation
patterns
during
zebrafish
embryonic
development.
We
assessed
general
toxicity
morphological
changes,
measured
global
hydroxymethylation
levels,
evaluated
methyltransferase
(DNMT)
enzyme
activity,
as
well
mRNA
expression
DNMTs
ten-eleven
translocation
(TET)
methylcytosine
dioxygenase
genes.
Additionally,
analyzed
genome-wide
in
larvae
using
reduced-representation
bisulfite
sequencing.
Our
assessment
revealed
no
toxicity,
but
a
statistically
yet
subtle
decrease
body
length
following
TMPP
EHDPP,
along
with
reduction
head
height
after
TPHP
exposure,
was
observed.
Eye
diameter
width
were
unaffected
by
any
OPFRs.
There
changes
levels
group,
showed
clear
effect
DNMT
expression.
However,
EHDPP
significantly
decreased
only
DNMT1
expression,
while
reduced
several
orthologues
TETs
larvae,
leading
aberrant
methylation.
Differential
occurred
primarily
introns
(43%)
intergenic
regions
(37%),
9%
10%
occurring
exons
promoter
regions,
respectively.
Pathway
enrichment
analysis
differentially
methylated
region-associated
genes
indicated
that
enhanced
biological
molecular
functions
corresponding
metabolism
neurological
KEGG
further
TPHP-mediated
potential
signaling
pathways
including
TGFβ,
cytokine,
insulin
signaling.
This
study
identifies
specific
brings
novel
insights
into
mode
action
TPHP.
Environmental Science & Technology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 29, 2025
Aryl
phosphate
esters
have
been
detected
throughout
the
natural
environment
and
in
human
blood
samples,
making
it
important
to
determine
health
risks
associated
with
exposure
triphenyl
(TPHP)
its
metabolite
diphenyl
(DPHP).
Here,
C57BL/6J
male
mice
were
exposed
TPHP
or
DPHP
for
12
weeks
at
estimated
daily
intake
doses
of
0.1
7
μg/kg
bw/day.
affected
levels
short-chain
fatty
acids
bile
gut,
enhancing
production
29
medium-
long-chain
liver
by
3.72-fold
significantly
increasing
hepatic
lipid
cholesterol
levels.
Metabolomic
molecular
analysis
confirmed
that
elevated
persisted
after
an
8
week
recovery
period.
Gut
microbiota-dependent
alterations
toxic
end
points
observed
TPHP-fed
mice,
as
supported
results
fecal
microbiota
transplantation.
In
DPHP-fed
serotonergic
glutamatergic
synapses
simultaneously
altered
intestine,
corresponding
reduction
five
brain
neurotransmitters
(15.4-60.8%).
Decreased
carbohydrate
insulin
resistance
mice.
These
suggest
affect
metabolism
via
different
modes,
mediated
through
gut-liver
axis,
providing
novel
insights
into
mechanisms
organophosphate-ester-mediated
metabolic
disruption.
Environmental Toxicology,
Год журнала:
2024,
Номер
39(6), С. 3400 - 3409
Опубликована: Март 7, 2024
Abstract
Triphenyl
phosphate
(TPhP),
a
chemical
commonly
found
in
human
placenta
and
breast
milk,
has
been
shown
to
disturb
the
endocrine
system.
Our
previous
study
confirmed
that
TPhP
could
accumulate
interference
with
placental
lipid
metabolism
steroid
hormone
synthesis,
as
well
induce
endoplasmic
reticulum
(ER)
stress
through
PPARγ
trophoblast
JEG‐3
cells.
However,
molecular
mechanism
underlying
this
disruption
remains
unknown.
aimed
identify
role
of
PPARγ/CD36
pathway
TPhP‐induced
disruption.
We
increased
accumulation,
total
cholesterol,
low‐
high‐density
protein
progesterone,
estradiol,
glucocorticoid,
aldosterone
levels,
genes
related
hormones
including
3βHSD1
,
17βHSD1
CYP11A
CYP19
CYP21
.
These
effects
were
largely
blocked
by
co‐exposure
either
antagonist
GW9662
or
knockdown
CD36
using
siRNA
(siCD36).
Furthermore,
an
ER
inhibitor
4‐PBA
attenuated
effect
on
progesterone
glucocorticoid
siCD36
reduced
stress‐related
levels
induced
TPhP,
BiP,
PERK,
CHOP.
findings
suggest
may
also
play
synthesis
TPhP.
As
our
shed
light
pathway's
involvement
disturbance
biosynthesis
cells,
further
investigations
potential
impacts
function
following
birth
outcome
are
warranted.
Critical Reviews in Environmental Science and Technology,
Год журнала:
2023,
Номер
54(15), С. 1117 - 1137
Опубликована: Дек. 20, 2023
Aryl-phosphate
flame
retardants
(APFRs),
a
subcategory
of
organophosphate
(OPFRs),
are
present
in
diverse
range
materials
including
plastic,
and
foam
products,
furniture,
electronic
waste.
Despite
their
widespread
use,
research
on
the
toxicity
APFRs
remains
limited.
In
order
to
clarify
more
clearly
environmental
health
risks
caused
by
APFRs,
this
review
provides
comprehensive
overview
occurrence
four
APFRs:
triphenyl
phosphate
(TPHP),
2-ethylhexyl
diphenyl
(EHDPP),
isobutyl
(IDPP),
(DPHP).
Regarding
it
seems
that
EHDPP
TPHP
act
different
ways
intestine,
but
both
cause
disorders
lipid
metabolism
liver.
On
contrary,
toxic
effects
IDPP
liver
may
be
similar,
specific
mechanisms
require
further
study.
At
same
time,
DPHP,
as
main
biotransformation
should
receive
attention
for
its
toxicity.
Prioritizing
investigation
vivo
transformation
particularly
DPHP
enhancing
study
APFRs'
biodegradation
crucial
comprehensively
assess
APFRs.
Journal of Applied Toxicology,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 18, 2024
Abstract
The
reliability
of
relative
quantification
RT‐qPCR
depends
upon
the
gene
interest
being
normalized
to
one
or
more
reference
genes,
with
assumption
that
chosen
genes
do
not
experience
altered
expression
experimental
conditions.
correct
choice
stable
is
critical
when
investigating
alterations
transcript
levels
following
exposure
endocrine
and
metabolic
disrupting
chemicals,
such
as
flame
retardant
triphenyl
phosphate
(TPhP).
This
study
assessed
stability
eight
TPhP
in
embryonic
cells
derived
from
rainbow
trout
(
Oncorhynchus
mykiss
).
β‐actin
actb
)
18s
rRNA
were
stable,
while
glyceraldehyde‐3‐phosphate
dehydrogenase
gapdh)
was
found
be
increased.
gapdh
a
popular
has
been
previously
used
literature
for
teleost
fish
models.
We
discuss
implications
upregulation
context
chemical.
Furthermore,
we
quantified
tumor
suppressor
p53
relation
different
use
an
example
report
on
how
discrepancies
findings
might
arise
depending
gene.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(15), С. 8110 - 8110
Опубликована: Июль 25, 2024
Dent
disease-1
(DD-1)
is
a
rare
X-linked
tubular
disorder
characterized
by
low-molecular-weight
proteinuria
(LMWP),
hypercalciuria,
nephrolithiasis
and
nephrocalcinosis.
This
disease
caused
inactivating
mutations
in
the