Reduction of oxidative damages induced by titanium dioxide nanoparticles correlates with induction of the Nrf2 pathway by GSPE supplementation in mice

Titanium dioxide nanoparticles (TiO2 NPs) are widely used to additives in cosmetics, pharmaceuticals, paints and foods. Recent studies have demonstrated that TiO2 NPs increased the risk of cancer and the mechanism might relate with oxidative stress. Grape seed procyanidin extract (GSPE) is a natural compound which has been demonstrated to possess a wide array of pharmacological and biochemical actions, including anti-inflammatory, anti-carcinogenic, and antioxidant properties. Our data show that GSPE prevents the changes of histopathology and biomarkers in heart, liver and kidney that occur in mice exposed to TiO2 NPs. After pretreatment with GSPE, the DNA damage, reactive oxygen species (ROS) generation and malondialdehyde (MDA) content in mice exposed to TiO2 NPs had statistically significant decreases in dose dependent manners. GSPE increased the expression of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), NAD(P)H dehydrogenase[quinine] 1(NQO1), heme oxygenase 1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC). We conclude that grape seed procyanidin extract prevents the majority of tissue and molecular damage resulting from nanoparticle treatment. The protective effect of GSPE may be due to its strong antioxidative activities which related with the activated Nrf2 and its down-regulated genes including NQO1, HO-1 and GCLC.