Biomedical Engineering Reference
In-Depth Information
Oberdorster performed the foremost investigations that inferred uncoated fullerenes to cause
oxidative stress in the brain and the depletion of glutathione levels in juvenile largemouth bass
species [87,88]. Nielsen et al. described fullerenes as a “sword” that elicits useful effects at low
concentrations, but at high concentrations they may be able to induce inflammation and serious
disorders like cancer [89]. They concluded that direct DNA-damaging effects are low, but the for-
mation of reactive oxygen species (ROS) may cause inflammation and genetic damage. Several
authors reviewed the literature involving fullerene toxicity beginning in the early 1990s to present
and conclude that very little evidence gathered since the discovery of fullerenes indicate that C
60
is toxic [90,91]. A study on fullerenes introduced into the abdominal cavity of mice concluded that
there was evidence of asbestos-like pathogenicity [92].
CoSayes et al. found that
in vivo
inhalation of C
60
(OH)
24
and nano-C
60
in rats gave no effect,
whereas, in comparison, quartz particles produced an inflammatory response under the same con-
ditions. Utilizing these water-soluble, C
60
fullerene suspensions, several studies have reported that
exposure to C
60
fullerenes causes toxicity in various organisms. Juvenile bass fish were reported to
have increased lipid peroxidation in the brain and glutathione depletion in their gills after being placed
in 0.5 ppm water-soluble C60 fullerenes for 48 h [93].
In vitro
studies have reported cytotoxicity in
human cells exposed to water-soluble C
60
fullerenes due to the production of ROS and lipid peroxida-
tion [94,95]. One
in vitro
study reports that less than 10% of the suspension is residual solvent and that
controls for this residual solvent did not contribute to reactive oxygen production or cell death [94].
The exponential increase in patent filings and publications indicates a growing industrial interest
in fullerenes that parallels an academic interest. The discovery of fullerenes has been compared
to the discovery of benzene by many researchers. Fullerenes bring novel, three-dimensional car-
bon structures to medicine that can be made tissue selective as well as act as potential therapeutic
agents. However, before reaching a conclusive, approved formulation, its toxicity issues need to be
met or comprehended completely.
11.4.3 t
ItaNIuM
d
IoxIde
Titanium dioxide (TiO
2
) has been extensively documented as a food additive or food colorant. With
the latest advancement in nanotechnology, the use of nanosized TiO
2
has been accelerated in the
field of cosmetics and pharmaceuticals and they are finding key roles in nanotech research due
to their unique physiochemical properties. TiO
2
nanocomposites have advanced medical biotech-
nology in the same fashion as they are improving microarray and imaging technologies [96-98].
Paunesku et al. described the
in vivo
and
in vitro
behavior of TiO
2
nanocomposites combined with
oligonucleotide DNA (size ~45 Å). These nanocomposites not only retained the intrinsic photo-
catalytic capacity of TiO
2
and the bioactivity of covalently attached oligonucleotide DNA, but also
possessed the chemically and biologically unique novel property of a light-inducible nucleic acid
endonuclease, which could become a new tool for gene therapy [99].
Literature infers the association of the alveolar uptake of TiO
2
NPs with inflammation, fibrosis,
and pulmonary damage, both
in vivo
and
in vitro
[100]. These toxic effects are deemed mainly to be
due to alveolar macrophages and polymorphonuclear leukocytes, which produce excessive amounts
of mediators such as ROS, proteases, cytokines, and so on [101,102]. In addition, cytotoxicity medi-
ated by TiO
2
NPs themselves has also been reported in several cultured cell lines, mainly resulting
from the formation of ROS [103,104]. Studies are available that demonstrates that the exposure to
TiO
2
NPs also results in elevated levels of lipid peroxidation; alveolar macrophage numbers; and
increased activities of glutathione peroxidase, glutathione reductase 6-phosphate glucose dehydroge-
nase, and glutathione
S
-transferase in rats [100]. Grassian et al. demonstrated that exposing mice to
TiO
2
NPs was essentially negative and showed reversible inflammation characterized by an increase
in alveolar macrophages in lungs [105]. It is believed that exposure to TiO
2
NPs can initiate an
inflammatory reaction and induce the inflammasome activation and release of inflammatory cyto-
kines through a cathepsin-B-mediated mechanism in mouse lungs [106].
