Influences of TiO2 nanoparticle and fipronil co-exposure on metabolite profiles in mouse intestines

Food contaminates, such as insecticide, may influence the toxicity of nanoparticles (NPs) to intestine. The present study investigated the combined toxicity of TiO₂ NPs and fipronil to male mouse intestine. Juvenile mice (8 weeks) were orally exposed to 5.74 mg/kg TiO₂ NPs, 2.5 mg/kg fipronil, or both, once a day, for 5 days. We found that both TiO₂ NPs and fipronil induced some pathological changes in intestines, accompanying with defective autophagy, but these effects were not obviously enhanced after TiO₂ NP and fipronil co-exposure. Fipronil promoted Ti accumulation but induced minimal impact on other trace elements in TiO₂ NP-exposed intestines. Metabolomics data revealed that the exposure altered metabolite profiles in mouse intestines, and two KEGG pathways, namely, ascorbate and aldarate metabolism (mmu00053) and glutathione metabolism (mmu00480), were only statistically significantly changed after TiO₂ NP and fipronil co-exposure. Five metabolites, including 2-deoxy-D-erythro-pentofuranose 5-phosphate, 5alpha-cholestanol, beta-D-glucopyranuronic acid, elaidic acid, and isopentadecanoic acid, and maltotriose, were more significantly up-regulated after the co-exposure, whereas trisaccharide and xylonolactone were only significantly down-regulated by the co-exposure. We concluded that fipronil had minimal impact to enhance the toxicity of TiO₂ NPs to mouse intestines but altered metabolite profiles.