Biomedical Engineering Reference
In-Depth Information
chronic exposure to silver causes argyria and/or argyrosis.
210
In vitro studies
using different cell lines have shown the toxicity of AgNPs number of in vitro
studies.
211-213
The size, shape, chemical composition, surface charge, solubil-
ity, and their ability to bind affect biological sites and their metabolic fate and
excretion influence the toxicity of NPs.
55,56
The high surface area to volume
ratio in metal NPs increases the potential release of metal ions in solution
214,215
but it is not clear if the toxicity of AgNPs results from released silver.
213
Some suggested that the AgNP toxicity is due to oxidative stress and indepen-
dent of silver ions
213
while other indicated that measured silver ion content
of the AgNP suspension could not fully explain the toxicity of the AgNPs in
suspension.
212,216
The studies conducted by Beer et al.
217
indicated that at low silver ion frac-
tions (2.6% and below) the toxicity of the AgNP suspension was significantly
higher than that of the supernatant, which could suggest an involvement of fac-
tors other than pure silver ions. The same observation was observed in a study
on copper oxide NPs (CuONPs) that had a higher toxicity than dissolved cop-
per ions.
218
In these studies the suspension of AgNP showed low amounts of
silver ions and the ionic fraction of the AgNP suspension could not explain the
observed toxicity. The Beer et al.
217
results indicated that there were no signifi-
cant differences in the proportion of apoptotic or necrotic cells after treatment
with AgNP suspension or AgNP supernatant. The study by Qu et al.
29
focused
on evaluating the mechanism of the antimicrobial property of AgNPs. Their
data indicated that the Ag
+
ions in solution could not be the only source of tox-
icity of the AgNPs. To elucidate the role of reactive oxygen species (ROS) in
the antibacterial mechanism of AgNPs, the antibacterial activity of AgNPs was
investigated in the presence of
N
-acetylcysteine (NAC) which is an effective
antioxidant containing a mercapto group. If ROS is the cause of AgNP toxic-
ity, the presence of NAC can prevent the oxidative damage induced by AgNPs.
In the absence of NAC, AgNPs alone killed ~50% and almost 99% when used
at 5 and 10 mg/L respectively. When combined with 10 mM NAC, cell death
decreased to 20% and 40% in the presence of AgNPs at 5 and 10 mg/L, respec-
tively. These results demonstrated that the antibacterial activity of AgNPs
was attenuated in the presence of the antioxidant NAC which is in agreement
with reports that NAC not only reduce the concentration of ROS in the culture
medium as a ROS scavenger, but also induces the production of glutathione
which is an important cellular antioxidant.
219
Thus, the presence of NAC as
ROS scavenger may have been responsible for the reduced antimicrobial activ-
ity of the AgNPs or it is equally possible that NAC induced the production of
glutathione.
29
These studies support the claim that ROS are partly responsible
for the antibacterial activity of AgNPs. Similarly, Foldberg et al.
211
indicated
that ionic and/or nanoparticulate silver induces ROS in A549 cells. In their stud-
ies, they concluded that the higher ROS production of cells treated with AgNP
supernatant is most likely due to the higher amounts of silver ions to which the
cells are exposed, where the same mass of silver was applied.
