LOWER AIRWAYS RESPONSE IN RATS TO A SINGLE OR COMBINED INTRATRACHEAL INSTILLATION OF MANGANESE AND NICKEL NANOPARTICLES AND ITS ATTENUATION WITH A BIO-PROTECTIVE PRE-TREATMENT

Nickel(II) oxide and multiple manganese species [manganese(II, III) oxide included], may be jointly present in welding fumes submicron fraction. Using laser ablation of 99.99% pure metallic plates in deionized water, suspensions of NiO and Mn₃O₄ nanoparticles with mean (±σ) diameters 30±12 nm and 32±10 nm respectively were created. Both suspensions were instilled intratracheally to rats, one immediately after another in alternating sequence or separately (another instillation being with water). The broncho alveolar lavage fluid (BALF) was obtained 24 h after. The increase in total BALF cells, alveolar macrophages (AM) and neutrophil leukocytes (NL) counts and especially in the NL/AM ratio (which is a reliable сomparison index of instilled particles cytotoxicity) was significantly higher at exposure to NiO than to Mn₃O₄. Semi-contact atomic force microscopy of cell surface topography demonstrated active endocytosis of NiO and Mn3O4 nanoparticles by pulmonary phagocytes. The higher pulmonary cytotoxicity of NiO as compared with Mn₃O₄ nanoparticles was also shown by increase in some lysosomal enzyme activities. Mathematical analysis revealed a sub-additive combined action of NiO and Mn₃O₄, judging by cellular indices, while judging by different biochemical indices additivity, sub-additivity or synergism were shown. In rats fed glutamate, glycine, acetyl cysteine, iodide and a Se-containing multivitamin preparation orally during 4 weeks before exposure to NiO+Mn₃O₄ (0.25 mg each), the latter evoked a significantly weaker NL recruitment than in rats so exposed without pretreatment.

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