Protective effects of lycopene on TiO₂ nanoparticle-induced damage in the liver of mice

Titanium dioxide nanoparticles (nano-TiO₂ ) is one of the most widely used and produced nanomaterials. Studies have demonstrated that nano-TiO₂ could induce hepatotoxicity through oxidative stress, and lycopene has strong antioxidant capacity. The present study aimed to explore if lycopene protects the liver of mice from nano-TiO₂ damage. Ninety-six ICR mice were randomly divided into eight groups. They were control group, nano-TiO₂ -treated group (50 mg/kg BW), lycopene-treated groups (5, 20, and 40 mg/kg BW), and 50 mg/kg BW nano-TiO₂ - and lycopene-co-treated groups (nano-TiO₂  + 5 mg/kg BW of lycopene, nano-TiO₂  + 20 mg/kg BW of lycopene, nano-TiO₂  + 40 mg/kg BW of lycopene). After treated by gavage for 30 days, the histopathology of the liver was observed. Liver function was evaluated using changes in serum biochemical indicators of the liver (AST, ALT, ALP); and the level of ROS was indirectly reflected by the level of SOD, GSH-Px, MDA, GSH, and T-AOC. TUNEL assay was performed to examine the apoptosis of hepatocytes. Proteins of p53, cleaved-caspase 9, cleaved-caspase 3, Bcl-2, and Bax as well as p38 were detected. Results showed that lycopene alleviated the liver pathological damage and reduced the injury to liver function induced by nano-TiO₂ , as well as decreased nano-TiO₂ -induced ROS. Meanwhile, lycopene mitigated apoptosis resulting from nano-TiO₂ , accompanied by the reversed expression of apoptosis-related proteins. Furthermore, lycopene significantly reversed the upregulation of p-p38 induced by nano-TiO₂ . In conclusion, this study demonstrated that nano-TiO₂ resulted in hepatocyte apoptosis through ROS/ROS-p38 MAPK pathway and led to liver function injury. Lycopene protected mice liver against the hepatotoxicity of nano-TiO₂ through antioxidant property.