Structure-Dependent Cytotoxic and Cytoprotective Effects of Molybdenum(VI) Schiff Base Complexes in the Neuronal Cells in Vitro

Coordination compounds with transition metals, especially of molybdenum, are promising cytoprotective agents. In this work, we analyzed the changes in HT-22 cell viability under the influence of molybdenum(VI) Schiff base complexes per se or in cellular injury induced by hydrogen peroxide (annexin V and propidium iodine staining assay). The results allowed to identify the most active compound with dioxidomolybdenum(VI) ion coordinated to Schiff base derived from 1S,2S-(+)-2-amino-1-(4-nitrophenyl)-1,3-propanediol and 5-methoxysalicylaldehyde, protecting the cells and possessing low cytotoxicity. We addressed a range of active concentrations (statistically significant effect from 5 µM to 50 µM) and the temporal characteristics of the effect (which is evident in 1-h preincubation regimen or adding the compound 1 h after hydrogen peroxide). Importantly, the effect was present at different levels of glucose in the medium and in cellular injury induced by glutamate. Less pronounced protective effect was seen in SH-SY5Y cells on the model of hydrogen peroxide-induced (but not in glutamate-induced) cytotoxicity. Among the possible mechanisms of cytoprotective activity, there is a direct interaction with hydrogen peroxide (measured by cyclic voltammetry), decrease in reactive oxygen species generation (DCFH-DA assay in HT-22 cells) and maintenance of catalase activity (assessed in lysates of HT-22 cells on the model of hydrogen peroxide-induced injury).