Toxicological Effects and Potential Therapeutics of Chronic Exposure to Polyurethane Nanoplastics in Caenorhabditis elegans

Despite growing concerns about the ecological and health risks of nanoplastics at environmentally relevant concentrations (ERCs), the effects of polyurethane nanoplastics (PU NPs) on environmental organisms remain unclear. This study assessed the toxicity of PU NPs in the μg/L range in <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) through chronic exposure. Our results showed that 10 μg/L PU NP exposure significantly reduced brood size, head thrashes, and body bends, while 100 μg/L PU NP exposure decreased lifespan, and 1000 μg/L PU NP exposure increased mortality in wild-type <i>C. elegans</i>. Analysis of oxidative stress showed that both 10 and 1000 μg/L PU NP exposures elevated reactive oxygen species (ROS), SKN-1::GFP, and GST-4::GFP levels. Notably, while ROS production rose at 1000 μg/L, SKN-1::GFP and GST-4::GFP expression decreased compared to the 10 μg/L group, suggesting a compensatory response in <i>C. elegans</i> at lower exposure levels. The expression of oxidative stress-related genes and phenotype of differentially expressed genes indicated that <i>C. elegans</i> was in a compensatory phase when exposed to 10 μg/L of PU NPs, participating in the protective response of <i>C. elegans</i> to PU NPs. However, when exposed to 1000 μg/L of PU NPs, <i>C. elegans</i> was in a decompensatory phase, participating in the toxic regulation of PU NPs. In addition, under 10 μg/L PU NP exposure, cinnamon essential oil (CIEO) can enhance the expression of more antioxidant enzymes, thereby increasing the protective effect. Under 1000 μg/L PU NP exposure, CIEO could alleviate the toxic response of <i>C. elegans</i> to PU NPs exposure by promoting the expression of <i>skn-1</i>. Molecular docking analysis showed that the main active component of CIEO, cinnamaldehyde (CID), has a strong affinity with SKN-1/Nrf2. Our study is the first to emphasize the toxic effects of PU NPs on environmental organisms at ERCs and that CIEO might serve as a potential antidote for nanoplastic poisoning.