Renal Injury and Nrf2 Modulation in Mouse Kidney Following Chronic Exposure to TiO2 Nanoparticles

TiO2 nanoparticles (NPs) are used in the food industry but have potential toxic effects in humans and animals. TiO2 NPs impair renal function and cause oxidative stress and renal inflammation in mice, associated with inhibition of nuclear factor erythroid-2-related factor 2 (Nrf2), which regulates genes encoding many antioxidants and detoxifying enzymes. This study determined whether TiO2 NPs activated the Nrf2 signaling pathway. Mice exhibited accumulation of reactive oxygen species and peroxidation of lipid, protein, and DNA in the kidney, coupled with renal dysfunction, glutathione depletion, inflammatory cell infiltration, fatty degeneration, and apoptosis. These were associated with increased expression of NOX4, cyclooxygenase-2, and nuclear factor-κB. Oxidative stress and inflammation were accompanied by decreased expression of Nrf2 and down-regulation of its target gene products including heme oxygenase 1, glutamate–cysteine ligase catalytic subunit, and glutathione S-transferase. Chronic TiO2 NP exposure is associated with suppression of Nrf2, which contributes to the pathogenesis of oxidative stress and inflammation.