Ministry of Health and Social Development of the Russian Federation
State Educational Institution Of Higher Professional Education
Saratov State Medical University named after V.I. Razumovsky
Authors’ of research
Saratov State Medical University n.a. V.I.
Razumovsky
N.A. Navolokin, A.B. Bucharskya, G.N.
Maslyakova,
Saratov State University
D.A. Gorin D.A., S.V. German
Actuality of research
• Nanoparticles
become widespread in the
environment and ingest by breathing, with food,
through the skin and by intravenous administration
(Oberdörster G. et al., 2005).
• Nanoparticles can have adverse health effects (Seaton
A., Donaldson K., 2005; Shvedova AA, Kisin ER,
2005).
• Medical products with nanomaterials can be
dangerous for the healths (Peters K., Unger RE, 2004).
• The medical results often are ignored if they
testify to the toxicity of nanomaterials used in
medicine (Moghimi SM et al., 2005).
• Scientific works about toxicity of nanoparticles
by morphological methods are rare in the
literature.
The purpose of the study
to investigate the morphological
changes in organs and transplanted
tumors of laboratory animals with
parenteral methods of
administration Fe nanoparticles.
Materials
and
methods
• Fe nanoparticles (20 nm ± 10) Zp = 30 mv covered
•
•
•
•
by citrate shell
White outbred male rats
Transplanted tumor of liver cancer PC-1
Morphological methods: Standard hematoxylineosin, histochemical techniques
MRI
Design of experiment
White outbred half-year-old male rats inoculated with liver cancer PC-1, citrate
coated iron nanoparticles (Fe3O4, 20 nm ± 10), Zp = -30 mv, were used in the study.
Animal experiments were performed in accordance with the guidance «International
Guiding principles for Biomedical Research Involving Animals» (2012). Animals with
tumor transplanted liver cancer PC-1 were divided into 3 groups (10 rats were in each
group). In the first group the nanoparticle solution was administered once
intravenously at a dosage of 0.2 mg / kg; in the second group the nanoparticle solution
was administered in a dosage of 16 mg/kg. The third group (comparison group)
received a single intravenous injection of 1 ml saline.
Parenteral administration
Liver
Heart
Spleen
Brain
Administration of Fe nanoparticles: results
The increase of liver and kidney weight was observed
macroscopically after administration of Fe nanoparticles,
due to the higher degree of venous congestion, the
development of vascular and degenerative processes in
hepatocytes and epithelial cells of the convoluted tubules.
Dystrophic and necrotic processes may depend on
disturbance of blood circulation due circulation of iron
nanoparticles in the lumen of blood vessels, and due to the
toxic influence of the tumor itself . Accumulations of iron
nanoparticles and hemosiderin were not found by this
method and the duration of administration.
Morphological changes in the tumor and MRT
• Statistically significant thinning of interalveolar septa and
emphysema with increasing blood supply vessels were
occured in the lungs. Clusters of nanoparticles were not
revealed, but a significant increase in the area of peribronchial
lymphoid infiltrates was noted, which indicates body’s
immune response to the introduction of foreign particles.
• The prevalence of predominance full-blooded pulp compared
over white pulp was noted in spleen after intravenous
administration. The bright active centers were detected in
follicules, which indicated the activation of B-lymphocytes
differenciation and their blast-transformation. A statistically
significant increase in the thickness of the mantle zone was
observed indicating the increasing in cooperation of T- and Blymphocyte and accumulation of B-lymphocytes of memory.
Thus, the citrate stabilized nanoparticles of iron causes the
immune stimulation in spleen.
Organs
parameter
control
comparison
Dosage NP Fe 20 Dosage NP Fe 16
Kupffer cells and Ito
8.37±2.7
8.9±0.523
6.82±0.47
lymphocytes
3.1±1.4
5.5±0.54
necrotic hepatocytes
0.87±0.7
3.5±0.454
S infiltrates (mm2)
0.017±
0.001
0.0057±
0.0021
0.068±
0.00529
0.0092±
0.00062
S glomeruli (mm2)
0.0032±
0.0001
0.0096±
0.00038
Epithelial height (mm)
0.0094±
0.0001
0.0099±
0.00025
S follicles (mm2)
0.107±0.016
0.167±0.018
2.85±0.31
**
26.8±0.818
**
0.58±0.161
**
0.0053±
0.000226
***
0.0063±
0.00016
***
0.0179±
0.00031
***
0.136±0.019
The thickness of the marginal zone
(mm)
8.37±2.7
0.0139±
0.0018
0.0189±0.0012
*
Morphometric changes in organs at group
intravenousgroup
administration
of iron nanoparticles
mg / kg
mg / kg
Liver
Lung
Interalveolar septa thickness (mm)
Kidney
Spleen
13.27±0.89
**
1.09±0.33
**
14.36±1.7
**
0.21±0.02
**
0.011±
0.0006
*
0.0073±
0.0005
***
0.017±
0.00049
***
0.22±0.027
***
0.03±0.039
***
Conclusions
The intravenous administration of citrate - stabilized
iron nanoparticles in a dosage of 20 mkg/kg leads to
disruption of blood supply to the organs, mainly due to
the plethora, while marked dystrophic cell damage is
observed in two main detoxification organs: in the liver
and kidneys. The immunostimulatory effects of iron
on the white pulp of the spleen and peribronchial
lymphoid follicles were established. Particles were
detected in the heart and brain, and their
accumulation in the tumor was significantly noted.
This data indicates that the selected dose is sufficient
for accumulation of the iron nanoparticles in tumor.
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•
•
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•
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