UDP-glucuronosyltransferase
1A9
(UGT1A9),
an
important
detoxification
and
inactivation
enzyme
for
toxicants,
regulates
the
exposure
level
of
environmental
pollutants
in
human
body
induced
various
toxicological
consequences.
However,
a
method
high-throughput
monitoring
UGT1A9
function
under
to
is
still
missing
date.
In
this
study,
1,3-dichloro-7-hydroxy-9,9-dimethylacridin-2(9H)-one
(DDAO)
was
found
exhibit
excellent
specificity
high
affinity
toward
UGT1A9.
Remarkable
changes
absorption
fluorescence
signals
after
reacting
with
were
observed
due
intramolecular
charge
transfer
(ICT)
mechanism.
Importantly,
DDAO
successfully
applied
monitor
biological
functions
response
not
only
microsomes
samples
but
also
living
cells
based
on
screening
method.
Meanwhile,
identified
that
disturbed
significantly
influence
retention
time
bisphenol
S/bisphenol
A
cells.
Furthermore,
molecular
mechanism
underlying
inhibition
by
these
pollutant-derived
disruptors
elucidated
docking
dynamics
simulations.
Collectively,
fluorescent
probe
characterize
responses
towards
developed,
which
beneficial
elucidating
health
hazards
from
new
perspective.
Ecotoxicology and Environmental Safety,
Год журнала:
2024,
Номер
271, С. 115960 - 115960
Опубликована: Янв. 16, 2024
Triphenyl
phosphate
(TPhP)
serves
as
a
major
organophosphorus
flame
retardant,
and
its
induced
neurodevelopmental
toxicity
has
attracted
widespread
attention,
but
the
mechanism
remains
unclear.
In
this
study,
we
involved
zebrafish
to
explore
new
of
TPhP
inducing
oxidative
stress
ferroptosis
promote
toxicity.
The
results
suggested
that
affected
embryonic
development,
reduced
number
neurons,
led
abnormal
neural
behavior
in
larvae.
also
ROS
accumulation,
activated
antioxidant
defense
signal
Nrf2
Keap1,
significantly
changed
activities
Acetylcholinesterase
(AChE),
Adenosine
triphosphatase
(ATPase)
glutathione
S-transferase
(GST).
addition,
zebrafish,
which
was
reflected
increase
Fe2+
content,
expression
GPX4
protein
genes
related
iron
metabolism
(gpx4a,
slc7a11,
acsl4b,
tfa,
slc40a1,
fth1b,
tfr2,
tfr1a,
tfr1b
ncoa4).
Astaxanthin
intervention
specifically
inhibited
levels,
reversed
SLC7A11
levels
thus
alleviating
by
TPhP.
partially
activity
AChE,
GST
neurodevelopmental-related
(gap43,
gfap,
neurog1
syn2a),
so
rescue
developmental
abnormalities
motor
disorders
More
interestingly,
mitochondrial
apoptosis-related
BAX,
anti-apoptotic
BCL-2,
Caspase3
Caspase9
altered
exposed
group,
could
be
intervention.
summary,
our
exposure
can
induce
ferroptosis,
thereby
causing
neurodevelopment
while
reverse
reduce
larvae
activating
Nrf2/Keap1/HO-1
signaling
pathway.
Environmental Science & Technology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 10, 2025
Safer
chemical
alternatives
to
bisphenol
(BP)
have
been
a
major
pursuit
of
modern
green
chemistry
and
toxicology.
Using
similarity-based
approach,
it
is
difficult
identify
minor
structural
differences
that
contribute
the
significant
changes
toxicity.
Here,
we
used
omics
computational
toxicology
features
associated
with
BP
analogue-induced
embryonic
toxicity,
offering
valuable
insights
inform
design
safer
alternatives.
The
zebrafish
acute
behavioral
effects,
concentration-dependent
transcriptome
analysis
17
analogues
were
tested,
structure
characteristics
key
biological
activities-induced
toxicity
explored.
BPE,
BPF,
BPP,
BPBP,
BPS
induced
lower
lethality
than
BPA.
And,
8
triggered
hyperactive
behavior
at
environmentally
human
relevant
concentrations.
phenol
rings
linked
via
hydrophobic
segments
("chain:alkaneBranch_neopentyl_C5")
disturbed
stress
response,
leading
lethality,
introducing
groups
on
meta
position
augmented
their
effects.
"3DACorr_TotChg_3"
physicochemical
feature
for
disorders,
3DACorr_TotChg_3
value
<
0.11
could
induce
by
perturbing
neurodevelopment
pathways.
This
study
provides
an
integrated
strategy,
combining
data-driven
profiling
mechanism-based
