Comparative Metabolomic Approaches to Nanoplastic Toxicity in Mammalian and Aquatic Systems.

Nanoplastics (NPs), emerging contaminants originating from the degradation of larger plastics, have raised significant environmental and health concerns due to their ability to penetrate biological barriers and disturb cellular homeostasis. Exposure to NPs has been shown to induce oxidative stress, mitochondrial dysfunction, and inflammatory responses in both mammalian and aquatic systems, ultimately leading to metabolic imbalance. Metabolomics, a comprehensive analytical approach focusing on small-molecule metabolites, provides a direct reflection of these biochemical alterations and offers critical insights into the mechanisms underlying NP-induced toxicity. This review summarizes recent metabolomic studies investigating nanoplastic toxicity across mammalian and aquatic organisms, highlighting commonly perturbed pathways such as lipid metabolism, arachidonic acid metabolism, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. These disruptions indicate that NPs impair energy production, lipid regulation, and redox balance. In mammals, polystyrene and polyethylene terephthalate nanoplastics have been shown to alter hepatic and intestinal metabolism and induce oxidative and inflammatory stress, while in aquatic species, similar metabolic disturbances occur in the gills, liver, and brain. Collectively, the evidence emphasizes metabolomics as a powerful approach for elucidating the molecular basis of nanoplastic toxicity and suggests that integration with other omics techniques is essential for comprehensive risk assessment and mechanistic understanding.