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Comparative experimental modeling of subchronic toxicity of
nickel (II) oxide and manganese (II,III) oxide nanoparticles
and the attenuation of their combined adverse effects with a
complex of bioprotectors.
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1The Medical Research Center for Prophylaxis and Health Protection in Industrial
Workers; 30 Popov Str., Ekaterinburg, 620014, Russia
2 The Institute of Natural Sciences, the Ural Federal University, Ekaterinburg 620000,
Russia
3 The Ural State Medical University; 17 Klyuchevskaya Str., Ekaterinburg 620109,
Russia
4Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences,
20 Sofia Kovalevskaya Str. ,Ekaterinburg 620990, Russia
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Keywords: nanoparticles, manganese (II,III) oxide; nickel (II) oxide; subchronic
toxicity; bioprotectors.
1. Introduction
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2. Materials and methods
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Testing of the in vivo genotoxicity with the Random Amplification of Polymorphic DNA
(RAPD) Test on blood nucleated cells.
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Choice of bioprotectors
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The doses and administration methods of these bio-protectors are given in Table 1.
Table 1.
Doses and the mode of administration of the bioprotectors tested in our
experiment
Bioprotectors Estimated dosage and the mode of
administration
+++ 1 g/kg (added to the fodder)
160 mg per rat (as a 1.5% drink instead of water)
' 12 mg per rat (added to the fodder)
)2'' 30 mg per rat (added to the fodder)
*
4.4 mg per rat (added to the fodder)
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4.0 mcg per rat (added to the fodder)
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2. Results
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Table 2
Total manganese and nickel contents of rat’s organs, mcg per g of dried tissue,
after repeated intraperitoneal injections of NiO-NPs or Mn3O4-NPsnanoparticles,
together or separately,and of their combination with background oral
administration of the BPC (X±s.e.)
Metal
GROUPS OF RATS given :
Control NiO-NPs Mn3O4-NPs NiO-
NPs+Mn3O4-
NPs
NiO-
NPs+Mn3O4-
NPs
and BPC
Liver
Manganese 1$$=,3. .$$=,(7 1",=,1$ .>,=,", 11=,$
Nickel $1=,.3 .(,=$".^6_ ">,=,",6$>,,=">,^ >3,=3.^6
Spleen
Manganese ">>,=1( $",,=(3 "3,,=>1 "3>$=("$ (,,="$$^6
Nickel "3.,=>7 (.13=>((^ $"3,=(.$ $.1=1" $."3=>71
Kidneys
Manganese $13=,73 ,,,=,.$^_",3,=(3^6,>,= .1=."6
Nickel >",=3. ",.,=$"$ .,,=3> 1.,="7 >.1=">
Brain
Manganese .,,=,(3 11=,7> ,13=1,^ 1.,=,> 7",=,>,^
Nickel (.1=,7. ">$=", 313="(. 3>,=".3 >.,=,.,6
13
Note:*. statistically significant difference from the control group; +. from the group given
NiO-NPs+Mn3O4-NPs (without the BPC); ○from the group given Mn3O4-NPs (p < 0.05 by
Student’s t-test)
Table 3
Total manganese and nickel renal excretion in rats after repeated intraperitoneal
injections of NiO-NPs or Mn3O4-NPs nanoparticles, together or separately, and of
their combination with background oral administration of the BPC, mcg per 24 hr)
(X±s.e.)
Metal GROUPS OF RATS given:
Control NiO-NPs Mn3O4-
NPs
NiO-
NPs+Mn3O4-
NPs
NiO-
NPs+Mn3O4-
NPs
and BPC
Manganese ,,.=,,3 ,,,>=,,,.6_ ,,.=,,6,3"=,^ ,">=,
Nickel "7=," $17=3$^6_ ,.$=,$^6.1="7^ (,>=."^6
Note:*. statistically significant difference from the control group; + from the group given
NiO-NPs+Mn3O4-NPs (without the BPC); ○from the group given Mn3O4-NPs; (p < 0.05 by
Student’s t-test )
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Table 4
Some functional indices for the condition of rat after repeated
intraperitoneal injections of NiO-NPs or Mn3O4-NPs nanoparticles
separately and of their combination with background oral
administration of the BPC (X±s.e.)
Index Control Mn3O4-NPs NiO-NPs NiO-NPs+
Mn3O4-NPs
NiO-NPs+
Mn3O4-NPs
and BPC
BPC
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#
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,1.=,,$ ,7,=,,$^6 ,>(=,,3 ,..=,,1 ,1>=,,( ,1"=,,3
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Note:*. statistically significant difference from the control group; + from the group given NiO-
NPs+Mn3O4-NPs (without the BPC); ○from the group given Mn3O4-NPs (p < 0.05 by Student’s t-test with
Bonferroni correction).
Table 5
Morphometric indices for tubular epithelium damage in the kidneys of
rats after repeated intraperitoneal injections of NiO-NPs or Mn3O4-NPs
nanoparticles, together or separately, and of their combination with
background oral administration of the BPC (X±s.e.)
18
GROUPS OF
RATS GIVEN
BRUSH BORDER LOSS
(% LENGTHWISE)
EPITHELIAL DESQUAMATION
(% LENGTHWISE)
Water (control) 3((=,7 ,,,=,
NiO-NPs ,$=1^ ,(>=,$.
Mn3O4-NPs 7,"=1^ ,">=,$"6
)%2)6$%(2) "$$="$^ "($=,^
)%2)6$%(2)6
*
1,>=1 ,,,=,6
Note:*. statistically significant difference from the control group; + from the group
given NiO-NPs+Mn3O4-NPs (without the BPC); p < 0.05 (p < 0.05 by Student’s t-test with
Bonferroni correction).
Table 6
Morphometric indices for the state of rat’s liver and spleen after repeated
intraperitoneal injections of NiO-NPs or Mn3O4-NPs nanoparticles, together or
separately, and of their combination with background oral administraon of the BPC
(X±s.e.)
INDICES GROUPS OF RATS
Contr
ol
NiO-NPs Mn3O4-
NPs
NiO-
NPs+Mn3O4-
NPs
NiO-
NPs+Mn3O4-
NPs
+ BPC
LIVER
Akaryotic
hepatocytes
per 100 liver
cells
"1$=,">
17$=,3^6 .,$=,("^
3($=,(^$$>=,$(6
Binucleated
hepatocytes
per 100 liver
cells
13=,..
($$=,.$6 >,$=,.,
>(,=,7" .",=,1"
19
Kupffer cells
per 100 liver
cells
"3=,33
,",=,.$6 "13=,(3^6
.$,=""^""=,16
SPLEEN
Red pulp to
white pulp
ratio
>$=( (3=,7^ 3"=$ $.=,(^ ."=$6
Number of
brown
pigment
micro
aggregates
per square
of the
Avtandilov’
s grid
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Table 7
Morphometric indices for the state of rat’s brain after repeated intraperitoneal
injections of NiO-NPs or Mn3O4-NPs nanoparticles, together or separately, and of
their combination with background oral administraon of the BPC (X±s.e.)
Neurons (%
%)
Control Mn3O4-NPs NiO-NPs NiO-NPs+
Mn3O4-NPs
NiO-NPs+
Mn3O4-NPs
and BPC
25
Nucleus caudatus
Without a
nucleolus
$,3,="11 .77,=17^6(1$.="(3^6.,$,="".^ $13=">76
With a
distinct
centrally
located
nucleolus
"3"=. 7$$=,7,^61,,=,(^6"$3=,73^ "$">=,76
Hippocampus (CA 1)
Without a
nucleolus
$,3,="$, 1,(3="$^ $3>=""61,(,=$13^ ($,="(^6
With a
distinct
centrally
located
nucleolus
(.(="7" $(=3^ $.=13^6,=$^ $,3=7.^6
Note:*. statistically significant difference from the control group; +. from the group given NiO-
NPs+Mn3O4-NPs (without the BPC); p < 0.05 (p < 0.05 by Student’s t-test with Bonferroni correction).
26
E>F -4 +++:*;&5'
4e(,,F +'+ < <2-
+ '-
E7. F -45++4)%$%( 0
+++:*;&5'4e(,,4
< +'0
+-
27
E,. F - 4 5+ +4 )%$%(
-* 0 +++:*;&5'
4e(,,4:+<
E>7;
Table 8
The coefficient of genomic DNA fragmentation in the blood nucleated cells of rats
after repeated intraperitoneal injections of NiO-NPs or Mn3O4-NPs nanoparticles,
together or separately, and of their combination with background oral
administration of the BPC (X±s.e.)
Control Mn3O4-NPs NiO-NPs NiO-NPs+
Mn3O4-NPs
NiO-NPs+
Mn3O4-NPs and
BPC
BPC
,("=,,, ,3=,,^ ,3=,,^ ,3,=,,^ ,(3=,,^6,(=,,
Note:*. statistically significant difference from the control group; +.from the group given NiO-
NPs+Mn3O4-NPs (without the BPC); (p < 0.05 by Student’s t-test).
28
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44
4. Discussion
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30
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Acknowledgements
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Conflict of Interest
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References
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