Sub-chronic oral exposure to titanium dioxide nanoparticles induces neurotoxicity in Wistar rats: evidence from mitochondrial, Micro-CT, and behavioral analyses

Abstract

Given their widespread use in food, cosmetics, pharmaceuticals, agriculture, and industry, titanium dioxide nanoparticles (TiO₂-NPs) pose a potential risk due to frequent and prolonged exposure, raising concerns about their impact on both human and environmental health. A few numbers of studies were interested to the neurotoxicity of TiO2 NPs through the oral pathway. This study aimed to evaluate the neurotoxic effects of sub-chronic oral exposure to TiO₂-NPs in Wistar rats and investigate their toxic mechanisms using an integrated approach that links structural, cellular, behavioral, and biochemical changes, contributing to a better understanding of their toxicity and helping to mitigate potential risks to human health and the environment. In this study, animals received daily oral gavage of TiO₂-NPs (31–15 nm) at doses of 215 or 500 mg/kg for 90 days. Oxidative stress markers were assessed using brain

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