Combined proteomic and metabolomic studies on the liver of Amur sturgeon Acipenser schrenckii under titanium dioxide nanoparticle exposure

Nanomaterials, particularly titanium dioxide nanoparticles (TiO₂-NPs), are extensively utilized across various industries. However, their environmental release has raised concerns regarding their potential ecological and environmental impacts. The reproductive toxicity of TiO₂-NPs in fish species has attracted considerable attention, yet conflicting research outcomes have been reported. We investigated the effects of TiO₂-NPs exposure on the liver of juvenile Amur sturgeon Acipenser schrenckii using label-free proteomic and untargeted metabolomic analyses. The experiment included a control group and three groups exposed to different concentrations of TiO₂-NPs (low, TL; medium, TM; high, TH). Compared to the control group, 9, 19, and 25 proteins and 35, 73, and 158 metabolites were differentially expressed in the TH, TM, and TL TiO₂-NP-exposed groups, respectively. The differentially expressed genes (DEGs) were enriched in the Kyoto Encyclopedia for Genes and Genomes (KEGG) pathways related to glycolysis and gluconeogenesis. Moreover, among the 126 correlated proteins, the most enriched pathways were associated with endocytosis and protein processing in the endoplasmic reticulum. Notably, syringic acid was significantly downregulated across all three TiO₂-NP-exposed groups. To obtain a comprehensive overview of the TiO₂-NP-induced expression changes, a co-regulated network of proteins and metabolites associated with TiO₂-NPs exposure was constructed. Exposure to TiO₂-NPs led to enrichment and alteration of pathways related to immune responses, including endocytosis, protein processing in the endoplasmic reticulum, and peroxisome proliferator-activated receptor (PPAR) signaling. In conclusion, our findings indicate that exposure to TiO₂-NPs might disrupt glucose metabolism and induce immune responses, thus contributing to our understanding of the environmental impacts of nanomaterials and highlighting the need for further research and development of potential mitigation strategies.