[Changes in proteome profiles of rat liver microsomes induced by silicon dioxide nanoparticles].

The effect of daily intragastric administration of an aqueous dispersion of silicon nanoparticles (NPs) (the dose range from 1.0 mg/kg to 100 mg/kg body weight for 28 days) to rats on the proteomic profile of liver microsomes has been investigated by 2D-electrophoresis followed by subsequent mass spectrometry identification. The liver microsomal fraction was isolated by differential centrifugation and its protein composition was analyzed by 2D-polyacrylamide gel electrophoresis. Identification of protein spots was carried out using MALDI-TOF mass spectrometric analysis. The mass spectrometry analysis revealed the protein GRP78 (78 kD glucose-regulated protein precursor), belonging to the family of heat shock proteins. This protein present in animals of the control group was not detected in NP-treated rats of group 2 (1 mg/kg body weight/day) and group 3 (10 mg/kg body weight/day). This protein predominantly localized in the liver cell endoplasmic reticulum and plasma membrane has the chaperone biological activity. Possible mechanisms of the effects of engineered nanoparticles on biosynthetic processes in the body are discussed.

[Toxicological and sanitary characterization of bentonite nanoclay].

Intragastric administration of nanoclay to rats during 28 days led to reductions in the relative weight of the liver, the activity of its conjugating enzymes, the antagonistic activity of bifidoflora, and the hyperproduction of colonic yeast microflora. The findings lead to the conclusion that nanoclays that may be present in foods must be the object of sanitary regulation.

[Effect of titanium dioxide nanoparticles on protein expression profiles in rat liver microsomes].

There was studied an influence of intragastric administration of titanium dioxide (anatase form) nanoparticles (NP) on protein expression profiles in rat's liver microsomes by methods of proteomics. Animals received water suspension of NP in doses from 0,1 to 10 mg per kg body weight intragastrically daily during 28 days. Microsomes were isolated from liver by means of preparative ultracentrifugation. Proteins composition was studied by 2D-electrophoresis in acrylamide gel. Protein spots were identified by MALDI-TOF analysis. The results demonstrated appearance of 53 new protein spots and disappearance of 19 spots in animals subjected to NP irrespective of their dose. In addition 25 new spots appeared and 3 disappeared in higher doses of NP when compared to low dose group and control animals. Mass-spectrum analysis showed presence of few polypeptides registered in international database among proteins expressed under influence of NP. One of this dominant expressed proteins corresponded to enzyme glutathione transpherase Mu 2 isoform (M=41,55 kD, pI=8,0). The conclusion was made of well advances of proteomic analysis in artificial NP influences on biosynthetic processes estimation.

[Studies of effects of aluminum oxide nanoparticles after intragastric administration].

Growing Wistar rats received intragastrically nanoparticles (NPs) of aluminum oxide (Al2O3) daily during 28 days at doses of 1 or 100 mg per kg body mass. There were studied body mass of animals, relative mass of internals, rate of protein macromolecules absorption in the gut, oxidative damage of DNA, pool of tissue thiols, activity of hepatic enzymes of xenobiotic detoxication system, biochemical and hematological blood indices, stability of lysosome membranes, condition of antioxidant defense system, apoptosis of hepatocytes. Conducted experiments didn't reveal any marked toxic action of Al2O3 NPs on rats after 28 days of administration both in high and low dose. Among effects probably related to NPs influence on animals there were lowering of relative liver and lung masses, decrease of hepatic thiol pool, activity of CYP1A1 isoform in liver and glutathione reductase in erythrocytes, increase of diene conjugates of fatty acids in blood plasma. Said shifts were small in magnitude, didn't come out of margins of physiological norm and didn't show any distinct relation to NPs dose. However considering great importance of this nanomaterial as probable environmental contaminant the studies of it's toxicity must be continued in conditions of low doses (less than 1 mg per kg body mass) for long period of time.

[Influence of dioxide titanium nanoparticles on immune system indicators in rats].

We investigated the possible influence of titanium dioxide TiO2 nanoparticles (NPs) (rutile form) on immunological parameters in rats. The experiment was carried out on 40 male Wistar rats, separated on 4 groups. Rats of 1 and 2 groups received intragastrically deionized water, 3 and 4 groups - aqueous dispersion of NPs in dose of 100 mg/kg body weight every day. Rats of 2 and 4 groups were immunized intraperitoneally with 100 mkg egg ovalbumin (OVA) on the 1st, 3rd and 5th days of the experiment. On day 21 was administered an additional 10 mkg OVA. In this study were assessed the concentration of specific IgG antibodies (humoral immune response), levels of IL-6, IL-10 and TNF-alpha, expression of lymphocyte antigens CD45RA, CD3, CD4, CD8, CD161alpha, phagocytic activity of neutrophils, lymphocyte apoptosis, hematology characteristics of blood. The studies showed that intra-gastric administration of rats with NPs in rutile form generates significant increase of humoral immune response against food antigen (p<0,05 according to the Student t-test). In the analysis of leukogram it was found a significant decrease of immature cells in immunized animals when exposed to NPs. Administration of NPs resulted in a significant decrease of the relative numbers of B-lymphocytes in immunized animals, and generated a significant increase in the phagocytic activity of peripheral blood neutrophils. Stimulation index of phagocytosis significantly increased at reception of NP by non-sensitized animals. Effects of NP rutile on levels of cytokine production (IL- 6, IL-10, TNF-alpha), on hematological characteristics of blood were insignificant both in intact and immunized animals. Thus, it is shown the intragastric administration of NP rutile has some influence on the specific and nonspecific unit of immune system in immunized and intact rats.

[Toxicological sanitary characterization of silver nanoparticles introduced in gastrointestinal tract of rats].

Water suspensions of silver nanoparticles were introduced intragastrically to growing male Wistar rats daily for 28 days. There were studied animals mass gain, relative masses of viscera, intestinal barrier resistance against protein macromolecules, DNA oxidative damage, tissue non-protein thiol levels, first and second phase of xenobiotic detoxication system activity, lysosomal membranes stability in liver together with routine blood biochemical and hematological indices and caecal's microbiocenose state. The data testifying to possible toxic risks, connected with reaction of silver's nanoparticles is obtained.

[Efficacy of using zinc oxide nanoparticles in nutrition. Experiments on the laboratory animal].

In experiments on rats there was researched bioavailability of zinc oxide (ZnO) nanoparticles. There were determined the content of Zn in blood serum and tibia, intestinal uptake of macromolecules of egg albumin, some hematological, biochemical and immune indices, liver cells apoptosis. The results obtained show that the uptake of nanoparticles of ZnO enables restoration of this microelement status damaged by zinc deficit diet.