Ototoxicity of polystyrene nanoplastics in mice, HEI-OC1 cells and zebrafish

Front Mol Neurosci. 2024 Feb 19:17:1345536. doi: 10.3389/fnmol.2024.1345536. eCollection 2024.

Abstract

Polystyrene nanoplastics are a novel class of pollutants. They are easily absorbed by living organisms, and their potential toxicity has raised concerns. However, the impact of polystyrene nanoplastics on auditory organs remains unknown. Here, our results showed that polystyrene nanoplastics entered the cochlea of mice, HEI-OC1 cells, and lateral line hair cells of zebrafish, causing cellular injury and increasing apoptosis. Additionally, we found that exposure to polystyrene nanoplastics resulted in a significant elevation in the auditory brainstem response thresholds, a loss of auditory sensory hair cells, stereocilia degeneration and a decrease in expression of Claudin-5 and Occludin proteins at the blood-lymphatic barrier in mice. We also observed a significant decrease in the acoustic alarm response of zebrafish after exposure to polystyrene nanoplastics. Mechanistic analysis revealed that polystyrene nanoplastics induced up-regulation of the Nrf2/HO-1 pathway, increased levels of malondialdehyde, and decreased superoxide dismutase and catalase levels in cochlea and HEI-OC1 cells. Furthermore, we observed that the expression of ferroptosis-related indicators GPX4 and SLC7A11 decreased as well as increased expression of ACLS4 in cochlea and HEI-OC1 cells. This study also revealed that polystyrene nanoplastics exposure led to increased expression of the inflammatory factors TNF-α, IL-1β and COX2 in cochlea and HEI-OC1 cells. Further research found that the cell apoptosis, ferroptosis and inflammatory reactions induced by polystyrene nanoplastics in HEI-OC1 cells was reversed through the pretreatment with N-acetylcysteine, a reactive oxygen species inhibitor. Overall, our study first discovered and systematically revealed the ototoxicity of polystyrene nanoplastics and its underlying mechanism.

Keywords: environmental ototoxicants; ferroptosis; hearing loss; inflammation; ototoxicity; polystyrene nanoplastics; reactive oxygen species.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (82371137, 81873697, 81400467, 81530030, and 81500797). Shandong Provincial Natural Science Foundation of China (ZR2021MB091, ZR2022MC149, and ZR2023QH402), the Training Program of Innovation and Entrepreneurship for Undergraduates of China (S202310440178). Science Fund of Shandong Laboratory of Advanced Materials and Green Manufacturing (Yantai) (AMGM2021F08). Shandong Provincial Graduate Quality Education Teaching Resources Project (SDYAL2022186 and SDYKC2023184). Binzhou Medical University teaching reform and research project (JYKTMP2021013).