Are in vivo and in vitro assessments of comparative and combined toxicity of the same metallic nanoparticles compatible, or contradictory, or both? A juxtaposition of data obtained in respective experiments with NiO and Mn₃O₄ nanoparticles

Comparative and combined damaging effects of NiO and Mn₃O₄ nanoparticles were estimated on cultures of several established human cell lines. The cytotoxicity indices used were: (a) reduction in cellular dehydrogenase activity, (b) decrease in the ATP-content, (c) for SH-SY5Y cells also decrease in the tyrosine hydroxylase content. The combined cytotoxicity was modeled using the Response Surface Methodology. When assessing the stability of metal oxide nanoparticles (MeO-NPs) in cultural media used by us, we found that the addition of the fetal bovine serum (FBS) to them renders NiO-NPs and, to even greater extent, Mn₃O₄-NPs exponentially slow soluble while without FBS their dissolution was virtually undetectable. At the same time, sedimentation of these MeO-NPs noticeably slowed down in the presence of the same FBS. We have found dependence of cell damage on concentrations of MeO-NPs and higher cytotoxicity of Mn₃O₄-NP compared with NiO-NP. Thus, comparative assessment of the NPs unspecific toxicity obtained in our animal experiments was reproduced by the "in vitro" tests. However, with respect to manganese-specific brain damage "in vivo" discovered previously, present experiments on neurons "in vitro" showed only a certain enhancing effect of Mn₃O₄-NP on the action of NiO-NP, but the role of NiO-NP in the combination prevailed.