Biomedical Engineering Reference
In-Depth Information
injection, showed none or only mild histological changes that indicate mild toxicities at highest dose
of nanorods (Chitta et al. 2009).
14.2.3.7 Toxicity of Carbon Black and Polystyrene
The RES in the liver is exposed to all nanoparticles absorbed from the GIT into the cardiovascu-
lar system, in view of the fact that all blood exiting the GIT goes into the hepatic portal vein that
directly diffuses through the liver. Nanoparticles with low toxicities, such as carbon black and
polystyrene, stimulate macrophages
via
calcium signaling and ROS to make proinflammatory cyto-
kines such as tumor necrosis factor alpha. Oxidative stress inhibited hepatocyte function and bile
formation, while proinflammatory cytokines are also associated with the pathology of liver diseases
(Brown et al. 2004).
14.2.3.8 Toxicity of ZnO Nanoparticles
Sharma et al. performed
in vivo
studies in mice to investigate the oral toxicity of ZnO nanoparticles.
Results showed that a significant accumulation of nanoparticles in the liver leads to cellular injuries
after the sub-acute oral exposure of ZnO nanoparticles (300 mg/kg) for 14 consecutive days. Orally
administered ZnO nanoparticles led to liver damage, as revealed by histopathological examination
which showed hepatocellular necrosis. This was also supported by elevated alanine aminotransfer-
ase (ALT) and alkaline phosphatase (ALP) levels in the serum. The levels of these enzymes rise in
serum when the liver is damaged. The unaltered levels of creatinine, blood urea nitrogen, and bili-
rubin in this study indicated normal renal functions in the ZnO nanoparticle exposed group (Sharma
et al. 2012). These results support the findings of Wang et al. (2008), who observed liver damage in
mice after the oral exposure of ZnO nanoparticles, although at a higher dose of 5 g/kg.
14.3
TOXICITY OF NANOMATERIALS ON THE KIDNEY
14.3.1 k
IdNey
M
orphology
The kidneys are responsible for the filtration of the blood. Their parenchyma is separated into two
sections, the cortex and the medulla (Figure 14.2a), which comprise different parts of the nephron,
the basic functional unit of the kidney (Figure 14.2b). Blood filtration occurs in the cortex through
the glomerulus, a structure formed of the glomerular capillary network (Figure 14.2c). The filtering
apparatus in the glomerular capillary network is composed of three consecutive elements that are
essential for physiological functions (Figure 14.2d). The first component is the highly fenestrated
endothelium. The fenestrations, 60-80 nm in size, are covered by a 200-300 nm thick glycocalyx
layer adsorbed onto the luminal side of the endothelium (Haraldsson et al. 2008). This flexible gly-
coprotein barrier is anchored on the surface of endothelial cells and restricts the passage of blood
components. The second structure that is essential in controlling the passage of solutes into the
urine is the glomerular basement membrane (GBM). It is a 240-370 nm hydrated, fibrous, network
layer of type IV collagen containing laminin, entactin, and proteoglycan, with high heparin and
chondroitin sulfate contents (Haraldsson et al. 2008). The fibrous mesh of collagen and the abundant
anionic charges dispersed in the GBM could together contribute to restrict fluid flux and the passage
of negatively charged solutes. However, it is now believed that the GBM alone cannot be responsible
for the high permeation selectivity of the glomerular filtration process (Haraldsson et al. 2008). The
third component of the glomerulus is the visceral layer of Bowman's capsule that is composed of
podocytes. These highly differentiated cells outline the glomerular capillaries.
Podocytes interact with the GBM via numerous inter-digitated foot processes that form filtration
slits (Haraldsson et al. 2008). Finally, the mesangial cells and their extracellular matrix form the
renal mesangium, which offers structural support to glomerular capillaries. They are derived from
smooth muscle cells and possess phagocytic properties to keep the GBM filter free of debris as well
as secretory functions solicited in case of glomerular injuries (Michael et al. 1980).
