Рівень показників імунної реактивності у крові щурів за умов одноразового внутрішньошлункового введення суміші наночастинок металів (Ag, Fe, Cu, двоокис Mn)

М. Є. Романько



M. Ye. Roman'ko


Metal nanoparticles (NPMe) in the form of colloidal dispersions - is one of the most bioavailable forms of Me in comparison with the traditionally used salts of  corresponding metals.

Research of potential risks of using nanomaterials may be adequate at the use of key system characteristics of a living organism that is susceptible to toxic effects.

Blood as one of the biological fluids in the body corresponds to qualitative and quantitative changes in its composition to any exogenous and endogenous factors, that is a unique biomarker, and the study of clinical and biochemical parameters of blood is one of the informative methods that allows to establish the transition of the physiological state of the organism to the pathological .

The aim of the research was to determine the level of indices of humoral and cellular immunity links in rat blood under conditions of one-time intragastric administration of a mixture of NPMe (Ag, Cu, Fe, Mn dioxide) in a dose range compared to a mixture of salts of corresponding metals.

The colloidal dispersions of the following NPMe were used in this work: nano-particles of Argentum (NPAg) – ~ 30 nm with an initial concentration of 86.4 μg/cm3; Ferrum Nanoparticles (NPFe) – ~ 100 nm, 3174.0 μg/cm3; Cuprum nanoparticles (NPCu) – ~ 70 nm, 2678.6 μg/cm3; nanoparticles of manganese dioxide (NP of dioxide Mn) – ~ 50 nm, 2785.0 μg/ cm3 by metal, respectively, obtained by chemical condensation by restoring the corresponding metal salts in an aqueous medium, which allows to obtaining stable aqueous dispersions of nanoparticles of a certain size.

The NPMe mixture contained NPAg, NPFe, NPCu, and NP of Mn dioxide in an aliquot ratio, with final concentration of 100 μg/cm3 by metal, respectively.

As a drug - comparison in the studies there was used a solution of a mixture of salts of the corresponding metals in the ionic form: AgNO3, (CuSO4 • 5H2O), (MnSO4 • 5H2O) and (FeSO4 • 7H2O) in an aliquot with a final concentration of 100 μg/cm3 by metal, respectively.

The studies were conducted in the vivarium conditions,  and in the Toxicological Monitoring Laboratory of the Department of Toxicology, Safety and Quality of the Agricultural Products of the NSC "IECVM" on 144 sexually mature male rats of the Wistar line, mass (200-250) g. On the principle of analogues, 6 groups of animals were formed, 24 rats in each.

Animals of the 1st and 2nd experimental groups were administered single-dose intragastrically with a probe a solution of mixture of  NPMe and salts of the respective metals in a dose of 0.3 mg/kg of body weight, III, IV and V  experimental groups – NPMe at doses exceeding the recommended biotic dose of the preparation in 3 , 3, 6.7 and 13.3 times (1.0, 2.0 and 4.0 mg/kg of body weight), respectively.

The animals of the control group were administered for analogues' wits the help of probe 2 cm3 / rat of physiological solution sodium hydroxide (NaCl).

To determine the level of hematological and biochemical blood parameters, on the 1st-, 3rd-, 7th- and 14th day after the administration of a mixture of metals in both forms, 6 rats from each group were decapitated under light chloroform anesthesia and blood samples were taken by total bleeding.

In the whole blood of experimental rats, the content of the form elements was determined, in blood plasma – the concentration of circulating immune complexes (CIC) of the average molecular weight and  seromucoids (Sm), the level of total protein, albumin, the fractions of globulins and cellular mediators, γ-interferon and interleukin-1β, respectively, were determined.

The statistical processing of the results was carried out using the Microsoft Excel 2003 application package (for Windows XP) using the Student's T-test (P<0/05).

By determination of the level of hematologic indices and indices of nonspecific resistance and cellular mediators of immune reactivity in rats, the biocompatibility of the mixture of NPMe (Ag, Cu, Fe, Mn dioxide) in a dose of 0.3 mg/kg of body weight has been proved, which in the future is expedient to be considered in the development of mineral food supplements in such a composition with directed adaptive immunomodulatory action.

Studied clinical and biochemical parameters of the blood came to the physiological levels in the rats at the end of the experiment, both at the introduction of solutions of a mixture of metals in both disperse forms in a biotic dose (0.3 mg/kg of body weight), and a mixture of NPMe – in a dose of 2.0 mg/kg of body weight, but due to the effect of the NPMe mixture at doses of 1.0 and 4.0 mg/kg of body weight – certain changes in the parameters did not have reverse dynamics until the end of the experiment, which indicates the selective dose immunotoxicity of the latter.

The oscillatory nature of the changes in the number of leukocytes, the decrease in the number of red blood cells against the background of moderate decrease in the hemoglobin content (27.4 and 17.6%), hyperglobulinemia, along with the excess formation of such immunotoxic metabolites as CIC of the medium molecular weight and seromucoids (50.8 and 30.5%) and markers of acute-phase immune reactivity – γ-interferon and interleukin-1β (in 2.9 and 2.4 times, (P≤0.05)) - in blood plasma of experimental rats indicates an aggravation of the pathological process with the development of inflammatory reactions due to the immunotoxic effects of the NPMe mixture  in doses of 1.0 and 4.0 mg/kg of body weight, respectively.

The obtained data became a prerequisite for an experiment to determine the effects of chronic effects of the NPMe mixture on the organism of laboratory animals, and knowledge of their biocompatibility and bioavailability is the basis for preclinical and clinical testing of nanoparticles as substances of veterinary preparations and feed bioadditives.

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