Effects of nano-titanium dioxide on calcium homeostasisin vivoandin vitro: a systematic review and meta-analysis

With the extensive application of titanium dioxide nanoparticles (TiO2 NPs), their impacts on calcium homeostasis have aroused extensive attention from scholars. However, there are still some controversies in relevant reports. Therefore, a systematic review was performed followed by a meta-analysis to explore whether TiO2 NPs could induce the imbalance in calcium homeostasis in vivo and in vitro through Revman5.4 and Stata15.0 in this research. Fourteen studies were included through detailed database retrieval and literature screening. Results indicated that the calcium levels were significantly increased and the activity of Ca2+-ATPase was significantly decreased by TiO2 NPs in vivo and in vitro. Subgroup analysis of the studies in vivo showed that TiO2 NPs exposure caused a significant increase in calcium levels in rats, exposure to large-sized TiO2 NPs (>10 nm) and long-term (>30 days) exposure could significantly increase calcium levels, and the activity of Ca2+-ATPase showed a concentration-dependent downward trend. Subgroup analysis of the studies in vitro revealed that intracellular calcium levels increased significantly in animal cells, exposure to small-sized TiO2 NPs (≤10 nm) and high concentration (>10 μg/mL) exposure could induce a significant increase in Ca2+ concentration, and the activity of Ca2+-ATPase also showed a concentration-dependent downward trend. This research showed that the physicochemical properties of TiO2 NPs and the experimental scheme could affect calcium homeostasis.