On the model of eukaryotic cells, it was found that NPAu of average size ~30 nm, NPAg - ~30 nm, NPFe - ~100 nm, NPCu - ~70 nm and NPMnO2- ~50 nm in the concentration range of 0.22-1061.00 ?g/ml by metal are safe due to the absence of genotoxic and membrane-toxic effects on eukaryotic test cells and mutagenic - on apical meristem Allium cepa. Experimental samples of NPCo, NPСо[Fe(CN)6] and NPZn by size of ~100 nm in the concentration range
0.12-830.00 ?g/ml by metal produce genotoxic effect (by the formation of tracks of the tail of the DNA comet and an increase in the level of the ІDNA), promutagenic with a decrease in the level of ІMIT and an increase in the number of aberrant cells (within 2.4-4.6 and 3.9-10.0 times) and membranotoxic activity (by reduction of membranous Na+, K+-ATPase activity by 19.7%; P<0.05).
By the nature of the changes in the enzymatic activity of the cell line U937 there was proved the discreteness of the membrane-toxic action of NPAu: particles ~10 nm in size caused the inhibition of the membrane Na+, K+-ATPase (up to 70 %), and particles ~30 nm and ~45 nm in size - its induction (within 20-40 %). During the testing of cytosolic LDGase activity there was determined its induction by
1.5-4.5 times with the action of NPAu in size of ~10, ~20 and ~30 nm and its inhibition by 5.0 times (P<0.05) - for the size of ~45 nm.
Under the influence of NPMe of size ~30 nm on the membrane fractions of cells Esherichia spp. and Salmonella spp. an increase in the level of total AOA was observed on average by 2.0 and 2.2 times; in general, the decrease in the activity of catalase up to 50.0 % (under the action of NPAu) and increase - up to 57.0 % (under the action of NPAg), growth activity of membrane Н+-ATPase and level of specific respiratory activity within 15.5-33.0 % and 10.7-32.6 %, (P<0.05) respectively. This has a regulatory effect on the level of formation of membrane-toxic products of LPO and carboxylic derivatives of OMР (P<0.05). Consequently, NPMe of ~30 nm in size are biocompatible and membranotropic for cells of eukaryotic and prokaryotic organisms. Whereas, NPAu of size ~20 and ~45 nm produce a prooxidant effect by testing cytological and biochemical markers.
The effect of the NPMe mixture on rats is shown, depending on the dose and duration of administration. It has been established that the toxic effect of the mixture of NPMe (Ag, Cu, Fe, MnO2) at a chronic administration in a dose of 1.0 and 4.0 mg/kg of body weight in the body of white rats leads to: hyperfermentemia of AST, GGTP, ALT and АP an average of 14.8; 22.3; 96.8 and 69.1 %), increase in the number of leukocytes on the background of reduction of erythrocytes and hemoglobin, hypoproteinemia (13.5 %), excessive formation of CIC and acute phase seromucoid proteins (by 36.1 and 62.8 %) and oxidative stress (with decreasing catalase activity and the level of total AOA of lipids (22.6 and 38.0 %), slowing the LPO process along with OMР intensification, (P<0.05) respectively. That is, the toxic effect of the mixture of NPMe and metal salts consists in the development of immunosuppression, inflammatory reactions and hepatotoxicosis through oxidative stress, in the prevalence of anabolic processes over catabolic, associated with adaptive mobilization of energy and purine metabolism, indicating the apparent intensification of removal and selective dosage tropism of metals in the body of animals. At a dose of 0.3 mg/kg of body weight, the NPMe mixture has adaptogenic effect by biocompatibility and bioavailability compared with the salts of the corresponding metals.
It has been proved the property of NPAu and NPAg of ~30 nm in size to have an inducing effect on the intensity of prokaryotic cells of production strains biomass growth after their lyophilization/rehydration. It was found that under the effect of NPAu and NPAg on E. coli cells the increase of the growth of biomass (by 28.8 and 22.3%) is accompanied by a decrease in the content of LPO products (strains 57 and 25) in their membranes and carboxylic derivatives OMР (strains 57, 25, 24 and 20) with an increase in the level of total AOA of lipids by 91.9 %, inhibition of catalase activity 1.5-4.5 times, induction of membrane Н+-ATPase 3.2 times and specific respiratory activity by 53.5 % (P<0.05). This gives grounds to consider such NPMe as protective substances because of their antioxidant effects, that is the experimental and theoretical basis for their use in obtaining biomass and as cryoprotectants during lyophilization of microorganisms. The level of accumulation of Escherichia spp., Pasteurella spp. and Salmonella spp. biomass after lyophilization and the vaccine strain B. anthracis under the effect of NPMe depends on the parameters of the structural and functional state of the membranes and with the participation of the energy metabolism resources of prokaryotic cells.
