Oxidative Damage Induced by Nano-titanium Dioxide in Rats and Mice: a Systematic Review and Meta-analysis

Nano-titanium dioxide is a kind of widely used nanomaterial that exhibits various adverse outcomes. However, the role of oxidative stress in this regard remains controversial. This study aimed to evaluate whether oxidative stress is one of the toxicity mechanisms induced by nano-titanium dioxide in rats and mice model. In this meta-analysis, 64 relevant publications were included through detailed database search. The pooled results showed that nano-titanium dioxide exposure could promote the expression of oxidants, such as malonaldehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), superoxide anion (O₂^-), and hydrogen peroxide (H₂O₂). Meanwhile, the levels of antioxidant-related enzymes and molecules, such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT), were reduced. Subgroup analysis revealed that different intervention routes, exposure periods, exposure dosages, and sample sources could affect the oxidative stress when exposed to nano-titanium dioxide. It was worth noting that the levels of MDA, 8-OHdG, and GSH significantly increased (P < 0.05) when the particle size of nano-titanium dioxide was < 10 nm, whereas H₂O₂, SOD, and GPx showed the highest effect at 10-40 nm. This study indicated that nano-titanium dioxide could cause oxidative damage by affecting the levels of enzymes and molecules involved in oxidative stress in rats and mice. And these results could provide a reference for studies of the toxicity mechanism induced by nano-titanium dioxide in the future.