Short-term oral exposure to low doses of nano-sized TiO₂ and potential modulatory effects on intestinal cells

The present study investigated potential modulatory effects of low doses of nano-sized titanium dioxide (TiO₂) on intestinal cells in vivo and in vitro. After short-term exposure to TiO₂ nanoparticles in rats, histopathological analysis of intestinal tissues indicated a gender-specific effect with increased length of intestinal villi in male rats only. Moreover the intestinal tissue showed nanoparticle deposition as revealed by ICP-MS determination of titanium. Increased serum testosterone levels were also detected. Considering the male-specific effects detected in vivo, the TiO₂ nanoparticle interaction with intestinal cells was further characterized in vitro and the modulating effect of testosterone and a hormone-induced growth factor, namely Insulin-like Growth Factor 1 (IGF-1), was also assessed. Cytotoxicity assays and analysis of Reactive Oxygen Species (ROS) production showed neither cellular alteration nor oxidative stress for nanoparticles at low concentrations, even though they were able to penetrate intestinal cells, as revealed by electron microscopy. Cell treatments with nanoparticles in association with testosterone or IGF-1 showed increased cell proliferation, compared to nanoparticles or testosterone/IGF-1 alone. Since long-term intake of TiO₂ nanoparticles at low doses is a relevant scenario for human exposure, attention should be given to the potential modulating activity of this nanomaterial on cell proliferation.