The Influence of Long-Term Dietary Intake of Titanium Dioxide Particles on Elemental Homeostasis and Tissue Structure of Mouse Organs

Background: Titanium dioxide (TiO2), consisting of nanoparticles and sub-microparticles, were widely used as food additive and consumed by people every day, which has aroused a public safety concern. Some studies showed TiO2 can be absorbed by intestine and then distributed to different tissues after oral intake, which is supposed to affect the content of various elements in the body whereas led to tissue damage. However, knowledge gaps still exist in the impact of TiO2 on the disorder of elemental homeostasis. Thus, this study aimed to explore the oral toxicity of TiO2 by assessing its influence on elemental homeostasis and tissues injury. Method: ICR mice were fed with normal feed, TiO2 nanoparticles (NPs)-mixed feed or TiO2 submicron particles (MPs)-mixed feed (1% mass fraction TiO2 NPs or MPs were mixed in commercial pellet diet) for 1, 3, and 6 months. Particles used in this study were characterized. The distribution of Ti and other 23 elements, the correlation among elements, and pathological change in the liver, kidney, spleen and blood cells of the mice was determined. Result: Ti accumulation only appeared in blood cells of mice treated with TiO2 MPs-mixed feed for 6 months, but TiO2 cause 12 kinds of elements (boron, vanadium, iron, cobalt, copper, zinc, selenium, sodium, calcium, magnesium, silicon, phosphorus) content changed in organ tissue. The changed kinds of elements in blood cells (6 elements), liver (7 elements) or kidney (6 elements) were more than in the spleen (1 element). The TiO2 NPs induced more elements changed in blood cells and liver, and the TiO2 MPs induced more elements changed in kidney. Significantly positive correlation between Ti and other elements was found in different organs except the liver. Organ injuries caused by TiO2 NPs were severer than TiO2 MPs. Liver exhibited obvious pathological damage which became more serious with the increase of exposure time, while kidney and spleen had slight damages. Conclusion: These results indicated long-time dietary intake of TiO2 particles could induce element imbalance and organ injury. The liver displayed more serious change than other organs, especially under the treatment with TiO2 NPs. Further research on the oral toxicity of TiO2 NPs should pay more attention to the health effects of element imbalances using realistic exposure methods.

ELEMENTAL HOMEOSTASIS IN WISTAR RATS AS A MANIFESTATION OF ADAPTATION IN AN EXPERIMENT WITH METAL LOADING IN THE FORM OF MICRO- AND NANOPARTICLES

Relevance. In recent years, various methods have been widely used to determine the state of adaptation.One of the mechanisms providing adequate adaptation reactions and resistance of the organism to the action of hazardous environmental factors is an increase in the number of intra- and intersystem connections between the content of macronutrients and trace elements, as a means of reliable functioning of the organism. Objective. To reveal the typical stages of adaptation of the organism of rats in different conditions of the action of metals by studying the correlation dependences between the content of macronutrients and trace elements in various biological media and assessing the degree of adaptation of the elemental system. Materials and methods. Determination of the content of 14 chemical elements in whole blood and endocrine organs was performed using microwave mineralization of samples and was determined by the OES-ICP method on an Optima 2100 DV device. The assessment of their ratios and the analysis of correlations between the elements and the assessment of the degree of resistance of the organism by calculating the index - the degree of adaptation of the elemental system of the organism (A) according to the formula of R.M. Baevsky were carried out. Results. The degree of a, sti of experimental animals to the action of Al and Ag, Cr and Mn compounds was estimated according to the proposed by R. M. Baevsky et al. [4] the formula, taking into account the correlations between of macronutrients and trace elements in biological media (degree of adaptation - A). During intraperitoneal administration of metal salts, they were characterized by a stress stage for Al and Cr, the training stages corresponded to a change in the balance of elements under conditions of Mn salt administration. No significant violations of adaptation were found under the conditions of Ag action. Under the conditions of oral administration of metal salts, the degree of adaptation was higher for Ag and Al compounds, the stress stage was characterized by the effect of Mn and Cr salts on elemental homeostasis. Comparison of the action of NPs metal showed a greater adaptation to the action of NPs of Al and Ag oxides and worse to the action of NPs of Mn and Cr citrates. Sex differences in adaptation of animals to the action of metal salts were also revealed. Thus, in males exposed to Al, adaptation was characterized by a training stage, while in females the response to Ag action corresponded to the stress stage. The latter gives grounds to assert that the thyroid gland is more sensitive to Ag than in males. Correlation dependences between the content of metals and hormones in animals, exposed to compounds Ag, Al, Cr, Mn, showed a multidirectional effect of Ag and Al on the correlation between the content of metal and hormone I-TG If a direct correlation was found in the control between the content of metals in the blood and free T4 for animals of all groups, and in the experiment only under the condition of exposure to Al and Cr. For the hormone C-peptide (insulin precursor), a significant correlation was found. The bond was found only under the condition of exposure to Al and Mn. Conclusions. For the first time, an approach was applied to assessing the adaptation of an organism in terms of the balance of macronutrients and trace elements as an intermediate link in the adaptation process of the endocrine system in animal experiments. Comparison of the action of metal NPs showed a greater adaptation to the action of NPs of Al and Ag oxides and worse to the action of NPs of Mn and Cr citrates. Comparison of the effects of MC effect of metal nitrates and NPs of their oxides and hydrates according to the degree of adaptation of the elementary system indicates a higher toxicity of AgNO3, Al (NO3) 3, while the degree of adaptation under the action of NPs Mn-Ctr and Cr-Ct indicates their higher toxicity. Females were found to be more sensitive to Ag2O NPs than males, and the opposite effect was found under the conditions of Al2O3 NPs. The data obtained testify in favor of the existing ideas about the higher toxicity of metals in the form of nanoparticles compared to microparticles, that is, NPs of manganese and chromium citrates are more toxic.

Intraspecific Variation in Nickel Tolerance and Hyperaccumulation among Serpentine and Limestone Populations of Odontarrhena serpyllifolia (Brassicaceae: Alysseae) from the Iberian Peninsula

Odontarrhena serpyllifolia (Desf.) Jord. & Fourr. (=Alyssum serpyllifolium Desf.) occurs in the Iberian Peninsula and adjacent areas on a variety of soils including both limestone and serpentine (ultramafic) substrates. Populations endemic to serpentine are known to hyperaccumulate nickel, and on account of this remarkable phenotype have, at times, been proposed for recognition as taxonomically distinct subspecies or even species. It remains unclear, however, to what extent variation in nickel hyperaccumulation within this taxon merely reflects differences in the substrate, or whether the different populations show local adaptation to their particular habitats. To help clarify the physiological basis of variation in nickel hyperaccumulation among these populations, 3 serpentine accessions and 3 limestone accessions were cultivated hydroponically under common-garden conditions incorporating a range of Ni concentrations, along with 2 closely related non-accumulator species, Clypeola jonthlaspi L. and Alyssum montanum L. As a group, serpentine accessions of O. serpyllifolia were able to tolerate Ni concentrations approximately 10-fold higher than limestone accessions, but a continuous spectrum of Ni tolerance was observed among populations, with the least tolerant serpentine accession not being significantly different from the most tolerant limestone accession. Serpentine accessions maintained relatively constant tissue concentrations of Ca, Mg, K, and Fe across the whole range of Ni exposures, whereas in the limestone accessions, these elements fluctuated widely in response to Ni toxicity. Hyperaccumulation of Ni, defined here as foliar Ni concentrations exceeding 1g kg−1 of dry biomass in plants not showing significant growth reduction, occurred in all accessions of O. serpyllifolia, but the higher Ni tolerance of serpentine accessions allowed them to hyperaccumulate more strongly. Of the reference species, C. jonthlaspi responded similarly to the limestone accessions of O. serpyllifolia, whereas A. montanum displayed by far the lowest degree of Ni tolerance and exhibited low foliar Ni concentrations, which only exceeded 1 g kg−1 in plants showing severe Ni toxicity. The continuous spectrum of physiological responses among these accessions does not lend support to segregation of the serpentine populations of O. serpyllifolia as distinct species. However, the pronounced differences in degrees of Ni tolerance, hyperaccumulation, and elemental homeostasis observed among these accessions under common-garden conditions argues for the existence of population-level adaptation to their local substrates.

Organ Metallome Processed with Chemometric Methods Enable the Determination of Elements that May Serve as Markers of Exposure to Iron Oxide Nanoparticles in Male Rats

The systemic influence of iron oxide nanoparticles on the elemental homeostasis of key organs was examined in male rats. In tissues taken at different intervals from nanoparticles injection, the dynamics of elemental changes was analyzed. The organ metallome was studied using total reflection X-ray fluorescence. The obtained data were processed with advanced cluster and discriminant analyses—to classify the tissues according to their organs of origin and to distinguish accurately the nanoparticle-treated and normal rats. Additionally, in the case of liver and heart, it was possible to determine the elements of highest significance for different treatments, which may serve as markers of exposure to iron oxide nanoparticles.

Intravenously administered d-mannitol-coated maghemite nanoparticles cause elemental anomalies in selected rat organs

In this study novel d-mannitol coated maghemite nanoparticles (MIONPs) are presented in terms of their influence on elemental homeostasis of living organisms and for this purpose highly sensitive total reflection X-ray fluorescence was used.