Effects of nano-titanium dioxide on calcium homeostasis in vivo and in vitro : a systematic review and meta-analysis.

With the extensive application of titanium dioxide nanoparticles (TiO 2 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 TiO 2 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 Ca 2+ -ATPase was significantly decreased by TiO 2 NPs in vivo and in vitro. Subgroup analysis of the studies in vivo showed that TiO 2 NPs exposure caused a significant increase in calcium levels in rats, exposure to large-sized TiO 2 NPs (>10 nm) and long-term (>30 days) exposure could significantly increase calcium levels, and the activity of Ca 2+ -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 TiO 2 NPs (≤10 nm) and high concentration (>10 μg/mL) exposure could induce a significant increase in Ca 2+ concentration, and the activity of Ca 2+ -ATPase also showed a concentration-dependent downward trend. This research showed that the physicochemical properties of TiO 2 NPs and the experimental scheme could affect calcium homeostasis.