Multi-omics analysis reveals mitochondrial dysfunction-driven oxidative stress pathways in Caenorhabditis elegans...

The widespread application of organophosphate flame retardants (OPFRs) in everyday products has resulted in significant environmental contamination. Among these products, Antiblaze V6 has been extensively utilized in plastic manufacturing because of its low toxicity. However, the molecular mechanisms of its toxic effects remain unclear. In this study, we conducted metabolomics and transcriptomics analyses to identify convergent and divergent key events associated with the potential toxicity of V6, with the aim of uncovering common patterns of these V6-related processes. We exposed Caenorhabditis elegans (C. elegans) to V6 and performed transcriptomics and metabolomics analyses. Preliminary experiments confirmed increased oxidative stress and mitochondrial dysfunction in C. elegans exposed to V6, indicating that mitochondrial impairment is a key feature of V6-induced toxicity. Overall, 62 metabolites were altered in C. elegans that were exposed to V6. The pathways associated with oxidative stress and mitochondrial dysfunction were conserved in C. elegans. Additionally, transcriptome analysis revealed that 2392 differentially expressed genes were primarily affected by V6 exposure; the major altered pathways were the TCA cycle, oxidative phosphorylation, and mitochondrial inner membrane pathways. Integrated transcriptomics and metabolomics enrichment analyses further confirmed the findings of the investigation of individual omics modalities. Collectively, our findings provide significant insights into the development of adverse outcome pathways in species that are exposed to V6 and the regulation of the potential toxicity of V6.