Toxicology Research,
Год журнала:
2024,
Номер
13(6)
Опубликована: Ноя. 5, 2024
Abstract
Background
Rapid
industrialization
globally
has
led
to
a
notable
increase
in
the
production
and
utilization
of
metals,
including
cadmium
(Cd),
consequently
escalating
global
metal
pollution
worldwide.
Cd,
characterized
as
persistent
environmental
contaminant,
poses
significant
health
risks,
particularly
impacting
human
health,
notably
functionality
kidneys.
The
profound
effects
Cd
stem
primarily
from
its
limited
excretion
capabilities
extended
half-life
within
body.
Mechanisms
underlying
toxicity
encompass
generating
reactive
oxygen
species
(ROS),
disrupting
calcium-signaling
pathways
impairing
cellular
antioxidant
defense
mechanisms.
This
review
focuses
on
protective
various
herbal
active
ingredients
against
Cd-induced
nephrotoxicity.
Aim
study
aims
investigate
mechanisms
action
ingredients,
ant-oxidative,
anti-inflammatory
anti-apoptotic
pathways,
elucidate
potential
therapeutic
strategies
for
reducing
nephrotoxicity
caused
by
exposure.
Methods
A
comprehensive
search
scientific
databases,
Web
Science,
PubMed,
Scopus
Google
Scholar,
used
relevant
keywords
identify
studies
published
up
October
2024.
Results
Research
illustrates
that
protect
oxidative
stress,
enhancing
enzyme
activity,
inhibiting
inflammation,
preventing
apoptosis,
alleviating
endoplasmic
reticulum
(ER)
autophagy
improving
mitochondrial
function
kidney.
Conclusion
present
indicates
an
extensive
understanding
holds
promise
development
innovative
approaches
safeguard
integrity
detrimental
Archives of Toxicology,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 20, 2024
Abstract
Heavy
metals
are
naturally
occurring
components
of
the
Earth’s
crust
and
persistent
environmental
pollutants.
Human
exposure
to
heavy
occurs
via
various
pathways,
including
inhalation
air/dust
particles,
ingesting
contaminated
water
or
soil,
through
food
chain.
Their
bioaccumulation
may
lead
diverse
toxic
effects
affecting
different
body
tissues
organ
systems.
The
toxicity
depends
on
properties
given
metal,
dose,
route,
duration
(acute
chronic),
extent
bioaccumulation.
detrimental
impacts
human
health
largely
linked
their
capacity
interfere
with
antioxidant
defense
mechanisms,
primarily
interaction
intracellular
glutathione
(GSH)
sulfhydryl
groups
(R-SH)
enzymes
such
as
superoxide
dismutase
(SOD),
catalase,
peroxidase
(GPx),
reductase
(GR),
other
enzyme
Although
arsenic
(As)
is
believed
bind
directly
critical
thiols,
alternative
hydrogen
peroxide
production
processes
have
also
been
postulated.
known
signaling
pathways
affect
a
variety
cellular
processes,
cell
growth,
proliferation,
survival,
metabolism,
apoptosis.
For
example,
cadmium
can
BLC-2
family
proteins
involved
in
mitochondrial
death
overexpression
antiapoptotic
Bcl-2
suppression
proapoptotic
(BAX,
BAK)
thus
increasing
resistance
cells
undergo
malignant
transformation.
Nuclear
factor
erythroid
2-related
2
(Nrf2)
an
important
regulator
enzymes,
level
oxidative
stress,
oxidants
has
shown
act
double-edged
sword
response
arsenic-induced
stress.
Another
mechanism
significant
threats
metal
(e.g.,
Pb)
involves
substitution
essential
calcium
(Ca),
copper
(Cu),
iron
(Fe))
structurally
similar
(Cd)
(Pb))
metal-binding
sites
proteins.
Displaced
redox
(copper,
iron,
manganese)
from
natural
catalyze
decomposition
Fenton
reaction
generate
damaging
ROS
hydroxyl
radicals,
causing
damage
lipids,
proteins,
DNA.
Conversely,
some
metals,
cadmium,
suppress
synthesis
nitric
oxide
radical
(NO
·
),
manifested
by
altered
vasorelaxation
and,
consequently,
blood
pressure
regulation.
Pb-induced
stress
be
indirectly
responsible
for
depletion
due
its
(O
·−
resulting
formation
potent
biological
oxidant,
peroxynitrite
(ONOO
−
).
This
review
comprehensively
discusses
mechanisms
effects.
Aluminum
(Al),
(Cd),
(As),
mercury
(Hg),
(Pb),
chromium
(Cr)
roles
development
gastrointestinal,
pulmonary,
kidney,
reproductive,
neurodegenerative
(Alzheimer’s
Parkinson’s
diseases),
cardiovascular,
cancer
(e.g.
renal,
lung,
skin,
stomach)
diseases
discussed.
A
short
account
devoted
detoxification
chelation
use
ethylenediaminetetraacetic
acid
(
EDTA),
dimercaprol
(BAL),
2,3-dimercaptosuccinic
(DMSA),
2,3-dimercapto-1-propane
sulfonic
(DMPS),
penicillamine
chelators.
Cadmium
(Cd)
is
a
neurotoxic
contaminant
that
induces
cognitive
decline
similar
to
observed
in
Alzheimer's
disease
(AD).
Autophagic
flux
dysfunction
attributed
the
pathogenesis
of
AD,
and
this
study
aimed
investigate
effect
autophagy
on
environmental
Cd-induced
AD
progression
underlying
mechanism.
Here,
Cd
exposure
inhibited
autophagosome-lysosome
fusion
impaired
lysosomal
function,
leading
defects
autophagic
clearance
then
APP
accumulation
nerve
cell
death.
Proteomic
analysis
coupled
with
Ingenuity
Pathway
Analysis
(IPA)
identified
SIRT5
as
an
essential
molecular
target
Cd-impaired
flux.
Mechanistically,
hampered
expression
SIRT5,
thus
increasing
succinylation
RAB7A
at
lysine
31
inhibiting
activity,
which
contributed
blockade.
Importantly,
overexpression
led
restoration
blockade,
alleviation
Aβ
deposition
memory
deficits,
desuccinylation
Cd-exposed
FAD
