Toxic effect of nickel in an in vitro model of human oral epithelium

Nickel is a metal widely employed in dental alloys, and due to peculiar properties of certain nickel-based materials, it cannot be substituted with other metals in some applications. The release of nickel ions from dental alloys placed into long-term contact with mouth soft tissues is alarming because of the toxic, immunological and carcinogenic effects which have been well documented for some nickel compounds. Our study was focussed on the toxic effects induced “in vitro” on human oral epithelium by the exposure to low concentrations of nickel chloride. In view of this, we adopted a three-dimensional model of epithelial cultures, reconstituted from TR146 cells, resembling the physiological environment of the oral cavity and useful for biocompatibility testing. The effects on cell viability, apoptosis, cellular content of reduced and oxidized glutathione (GSH and GSSG) and release of prostaglandin E2 (PGE2), interleukin-8 (IL-8) and interleukin-6 (IL-6) were investigated following topical application of a NiCl2 solution ranging from 7.6 mM to 0.05 mM for 72 h. Our findings show that nickel concentrations, which do not significantly modify cell viability and inflammation mediator release, can affect the redox equilibrium and stimulate apoptosis in oral epithelium cells. Further studies are needed to demonstrate the hypothesis that the oxidative imbalance induced by nickel might be implicated in the induction of apoptosis.