On the contribution of the phagocytosis and the solubilization to the iron oxide nanoparticles retention in and elimination from lungs under long-term inhalation exposure.

The aim of our study was to test a hypothesis according to which the pulmonary clearance vs. retention of metal oxide nanoparticles (NPs) is controlled not only by physiological mechanisms but also by their solubilization which in some cases may even prevail. Airborne Fe2O3 NPs with the mean diameter of 14±4nm produced by sparking from 99.99% pure iron rods were fed into a nose-only exposure tower. Rats were exposed to these NPs for 4h a day, 5days a week during 3, 6 or 10 months at the mean concentration of 1.14±0.01mg/m(3). NPs collected from the air exhausted from the exposure tower proved insoluble in water but dissolved markedly in the cell free broncho-alveolar lavage fluid supernatant and in the sterile bovine blood serum. The Fe2O3 content of the lungs and lung-associated lymph nodes was measured by the Electron Paramagnetic Resonance (EPR) spectroscopy. We found a relatively low but significant pulmonary accumulation of Fe2O3, gradually increasing with time. Besides, we obtained TEM-images of nanoparticles within alveolocytes and the myelin sheaths of brain fibers associated with ultrastructural damage. We have developed a multicompartmental system model describing the toxicokinetics of inhaled nanoparticles after their deposition in the lower airways as a process controlled by their (a) high ability to penetrate through the alveolar membrane; (b) active endocytosis; (c) in vivo dissolution. To conclude, both experimental data and the identification of the system model confirmed our initial hypothesis and demonstrated that, as concerns iron oxide NPs of the dimensions used, the dissolution-depending mechanisms proved to be dominant.

[Effectiveness of glutamate in the treatment of early manifestations of occupational fluorosis]. / Otsenka effectivnosti glutaminovoi kisloty kak sredstva korrektsii rannikh proiavlenii professionalnogo fliuoroza.

Efficiency of glutamic acid for therapy of early signs of occupational fluorosis was studied in workers engaged into cryolite production. The study proved that use of glutamic acid in occupational conditions prevents progressing of metabolic disorders. The results encourage recommendations to include glutamate into therapeutic and prophylactic nutrition of workers exposed to fluor compounds, into nutritive additions according to special recipe.

[The toxicokinetics of low-solubility substances (exemplified by 2 boron compounds)]. / K voprosu o toksikokinetike malorastvorimykh veshchestv (na primere dvukh soedinenii bora).

Multichamber toxicokinetic model studies of the resorption, distribution and excretion properties of poorly soluble substances in subchronic action of suspensions administered intragastrically can be the first step in prognosing the toxicokinetic properties of the inhaled aerosols of the substances mostly discharged from the respiratory into the gastrointestinal tract (GIT). The generally accepted quantitative characteristics of the particles' deposition and translocation into GIT can provide a further application of the model for a mathematical description of a prolonged inhalational exposure to some substances. This technique was tested with the boron compounds characterized by low solubility and revealed a good correlation between the prognosed and actual deposits of the substance in the organ and excretions. At the same time, detected were some qualitative and quantitative differences in the boron toxicokinetics influenced by magnesium deboride and hexaborate, which were explained by differences in their solubility.

[A multi-chamber model of quartz dust kinetics in the pulmonary region during chronic inhalation exposure in rats]. / Mnogokamernaia model' kinetiki kvartsevoi pyli v pul'monarnoi oblasti pri khronicheskoi ingaliatsionnoi ékspozitsii krys.

The contributors propose a multichamber model for the assessment of dust particles' concentration, elimination and translocation in deep pulmonary zones. The choice of the model structure is dominated by the following criteria: that dust penetration into the interstitial pulmonary tissues and its translocation to the lymph nodes can be performed by non-phagocytized particle only; that these processes depend on the degree of dust-induced lesions in the macrophages and the growth of compensating neutrophilic phagocytosis; that part of the penetrating particles would continuously return to the free surface of the pulmonary zone together with the mobilized interstitial lung macrophages. The model adequately corresponds to the experimental data obtained in prolonged inhalation experiments, and imitates the kinetic effects related to severe damages and protection of the pulmonary clearance macrophage mechanisms.

Development of a multicompartmental model of the kinetics of quartz dust in the pulmonary region of the lung during chronic inhalation exposure of rats.

A multicompartmental model for the kinetics of dust retention in the pulmonary region of the lung and in the tracheobronchial lymph nodes has been developed. The model reflects the following ideas concerning the basic features of this process: (1) penetration into the pulmonary interstitium and translocation to the lymph nodes are possible for non-phagocytized particles only; (2) these processes depend on the degree of damage to macrophages by dust and on the extent of compensatory enhancement in the recruitment of neutrophils taking part in the clearance of the pulmonary region free surface; (3) a certain proportion of initially penetrating particles is continuously returned to this surface together with recruited pulmonary macrophages. The model ensures a satisfactory approximation to experimental data on the retention of quartz in the lung and lymph nodes during long term inhalation exposure, and simulation of the kinetic effects associated with both the damage to and the protection of the macrophagal clearance mechanism.