Co-Exposure to Food-Grade and Nano-TiO2 with High-Fat Diet Induces Multi-Organ Injury in Liver, Intestine, Brain, and Testicles.

Titanium dioxide nanoparticles (TiO2 NPs), widely used as food additives, frequently coexist with high-fat diets (HD) in modern dietary patterns, yet their combined in vivo toxicity remains poorly understood. This study investigated the multi-organ effects of co-exposure to TiO2 NPs or food-grade E171 and HD in male C57BL/6J mice. Mice were randomly assigned to six groups and fed regular or high-fat diets containing 1 wt% TiO2 NPs or E171 for 13 weeks. Histopathology, serum biochemistry, organ coefficients, and open-field behavioral tests were used to assess tissue injury and functional alterations. Co-exposure to TiO2 NPs and HD markedly exacerbated tissue damage across multiple organs. In the liver, more severe ballooning degeneration, necrosis, and inflammatory infiltration were observed, accompanied by altered liver enzymes and reduced organ coefficients. Intestinal injury was characterized by crypt distortion and increased inflammation, particularly in the HD + TiO2 group. Testicular tissues showed disorganized seminiferous tubules, loss of spermatogenic cells, and interstitial hyperplasia. In the brain, hippocampal neurons exhibited pyknosis and disarray, with decreased brain coefficients and impaired exploratory behavior. E171 induced similar but milder effects. These findings indicate that HD enhances TiO2 NPs induced multi-organ toxicity, highlighting the health risks of realistic co-exposure to dietary nanoparticles and high-fat foods.