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.