Biomedical Engineering Reference
In-Depth Information
from the spleen was slower than from other organs. Histology and hematology results showed that
the spleen was slightly affected by the injection of the Gd(OH)
3
nanorods; there was a slight hyper-
plasia in the periarteriolar lymphoid sheath of the white pulp which may be caused by a nanotoxicity
effect of the Gd(OH)
3
nanorods. This phenomenon has previously been observed in other nanopar-
ticle-treated spleen tissues (Xiong et al. 2010).
14.4.3.3 Toxicity of Silica Nanoparticles
Sergey et al. carried out an experiment to study the
in vivo
toxicity of intravenously administered
silica and silicon nanoparticles (nano-SiO
2
). Most of the
in vivo
studies demonstrated the accumu-
lation and persistence of nano-SiO
2
in macrophages of the liver and spleen, which was associated
with a variable degree of inflammatory responses. The determinants of the observed toxicity are
complex and include dose, surface area, particle size, and treatment regimen. The single intravenous
administration of 11-15 nm nano-SiO
2
to rats at a dose of 7 mg/kg resulted in granuloma formation
and mononuclear infiltration in the liver and spleen that persisted for 60 days post-injection. Silica
and silicon nanoparticles were shown to cause granuloma formation in the organs of the RES, such
as the liver and spleen (Sergey et al. 2012).
14.4.3.4 Toxicity of TiO
2
Nanoparticles
Li et al. studied splenic injury in mice induced by the intraperitoneal injection of TiO
2
NPs for 45
consecutive days and investigated the pathological changes in the spleen, the expression levels of the
apoptotic genes, apoptosis and their proteins, and oxidative stress in the spleen. It was demonstrated
that TiO
2
NPs had an obvious accumulation in the mouse spleen, resulting in the congestion and
lymph nodule proliferation of splenic tissue and splenocyte apoptosis. TiO
2
NPs effectively acti-
vated caspase-3 and -9, decreased the Bcl-2 levels of genes and proteins, and increased the levels of
cytochrome c genes and Bax and their protein expression, and promoted the accumulation of ROS.
TiO
2
NPs induced apoptosis in mouse splenocytes via mitochondrial-mediated pathways leading to
the reduction of immunity (Li et al. 2010).
14.4.3.4.1 The pathway suggested
Intraperitoneal injections of various doses of TiO
2
NPs increased coefficients of the spleen, and its
significant accumulation in the mouse spleen induced histopathological changes of spleen, including
congestion and lymph nodule proliferation. The swelling of splenocyte mitochondria was observed,
splenocyte nuclei exhibited the classical morphology characteristics of apoptosis or necrosis: A
reduction in nuclear size, chromatin condensation, and the appearance of a nucleolus cap. The
swelling of the mitochondria suggested that TiO
2
NPs enter the cell, bind to the mitochondria, and
lead to structural changes and subsequent effects (Li et al. 2010).
Apoptosis is an important way to maintain cellular homeostasis between cell division and cell
death. It is well known that apoptosis can be triggered via two principal signaling pathways: The
death receptor-mediated extrinsic apoptotic pathway and the recruitment of adaptor proteins, fol-
lowed by activation of caspase-8 and the mitochondrion-mediated intrinsic apoptotic pathway.
Previous investigations have revealed that TiO
2
NPs induced the apoptosis of the hepatocytes (Ma
et al. 2009; Li et al. 2010), and speculated that the induction of apoptosis may be through the
mitochondria-mediated pathway, in which mitochondrial permeability transition is promoted, fol-
lowed by the release of apoptogenic factors such as apoptosis-inducing factor, cytochrome c, and
caspases-3 and -9. The Bcl-2 family of proteins have also been considered as critical regulators of
mitochondria-mediated apoptosis by functioning as either promoters (e.g., Bax and Bid) or inhibi-
tors of cell death process (Suliman et al. 2001; Kandasamy et al. 2003; Yao et al. 2008).
As per the study, TiO
2
NPs were potent inducers of the expression of caspase-3 and -9 genes and
their proteins in the mouse spleen, but did not alter caspase-8 expression. The mice treated with
TiO
2
NPs showed obviously enhanced levels of Bax, the release of cytochrome c from the mito-
chondria to the cytosol, and a concomitant reduction of Bcl-2 levels. The extent of the alterations
