Biomedical Engineering Reference
In-Depth Information
and quartz were almost equal (39.85 ± 2.58 μg/mL), indicating the comparable cytotoxicity of car-
bon nanoparticles with quartz particles.
The damage to the cell membrane induced by carbon nanoparticles was also monitored by the
lactate dehydrogenase enzyme (LDH) leakage assay, as LDH, a stable cytosolic enzyme in normal
cells, can leak into the extracellular fluid only after membrane damage. Exposure to MWCNTs and
quartz particles (10-100 μg/mL) for 48 h gave rise to a greater LDH release from human embryonic
kidney (HEK) cells. The analysis of the particle exposure media for LDH demonstrates that carbon
nanomaterials increase LDH leakage in a dose-dependent manner at a 48 h exposure period.
Concomitant cellular oxidative stress was manifested by reduced glutathione (GSH) levels and
an increased lipid peroxidation. The contrary linear relationship between the exposure concentra-
tion and the GSH level indicated that the exposure to carbon nanoparticles reduced intracellular
glutathione levels (
p
< 0.01). Moreover, the increased levels of thiobarbituric acid reactive sub-
stance content resulted in the production of malondialdehyde, an indication of lipid peroxidation.
MWCNT exposures to HEK cells produced a concentration-dependent cytotoxicity. The exposure
of MWCNTs to HEK cells resulted in cell membrane damage, increased lipid peroxidation, and
decreased intracellular glutathione levels, indicating that oxidative stress contributes to MWCNTs
induced cytotoxicity in HEK cells (Reddy et al. 2010).
14.3.4.5 Toxicity of Titanium Dioxide Nanoparticles
Titanium dioxide (TiO
2
) as an inert, nontoxic pigment product, is biologically inert and used in
cosmetics, paint, and building materials (Gillian et al. 2007).
In vivo
studies of the oral uptake of
TiO
2
have shown it to enter blood circulation, leading to kidney and liver damage, severe pulmonary
inflammation (Oberdörster et al. 2005), and emphysema.
Suxing et al. carried out a study to investigate the molecular mechanism of kidney injury in mice
caused by the intragastric administration of TiO
2
nanoparticles (TiO
2
NPs). The results showed that
TiO
2
NPs were accumulated in the kidneys, resulting in cell necrosis, nephric inflammation, and
dysfunction. Nucleic factor-κB was activated by TiO
2
NPs exposure; promoting the expression of
macrophage migration inhibitory factor; tumor necrosis factor-α; interferon-γ; interleukins-1β, -2,
-4, -6, -8, -10, and -18; cross-reaction protein; transforming growth factor-β; and CYP1A1; while the
expression of heat-shock protein 70 was inhibited. These findings implied that the TiO
2
NP-induced
nephric injury in mice might be associated with the alteration in the expression of inflammatory
cytokines and reduced detoxification of TiO
2
NPs (Suxing et al. 2011). Previous studies indicated
that abnormal pathological changes in the mouse kidney and nephric dysfunction were not able
to be triggered by the intraperitoneal injection of 5 mg/kg body weight TiO
2
NPs for 14 days, but
with 50, 100, and 150 mg/kg body weight TiO
2
NPs exposure, impairment of kidney functions, and
severe inflammatory response in the kidneys were observed (Zhao et al. 2010).
Numerous studies have demonstrated that damage to the kidneys of mice can be caused by expo-
sure TiO
2
NPs. Wang et al. observed that the exposure to TiO
2
NPs to mice resulted in higher blood
urea nitrogen and creatinine levels and the renal tubule was filled with proteinic liquids (Wang et al.
2007). Chen et al. also observed the dilatation of the renal glomerulus and proteinic liquid-filled
renal tubule, but no kidney dysfunction was found in TiO
2
NP-treated mice (Chen et al. 2009).
Furthermore, TiO
2
NPs were also suggested to induce nephric inflammation and impair nephric
functions, which exerted its toxicity through ROS accumulation (Zhao et al. 2010). However, the
molecular mechanism of TiO
2
NP-induced nephric injury remains unclear.
Acute toxicity with kidney injuries is also obtained with TiO
2
NPs in mice after oral or intraperi-
toneal administration (Wang et al. 2007; Chen et al. 2009).
14.3.4.6 Toxicity of Silica Particles
Omar et al. studied the effects of orally administered silica nanoparticles (nano-SiO
2
) in a rat
model in terms of biodistribution, toxicity, and changes to the elemental composition of feces
and organs. A response to the administration of silica was observed in the rats as a change in
