Plastics contaminations are found globally and fit the exposure profile of the planetary boundary threat. The plasticizer of dibutyl phthalate (DBP) leaching has occurred and poses a great threat to human health and the ecosystem for decades, and its toxic mechanism needs further comprehensive elucidation. In this study, environmentally relevant levels of DBP were used for exposure, and the developmental process, oxidative stress, mitochondrial ultrastructure and function, mitochondrial DNA (mtDNA) instability and release, and mtDNA-cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway with inflammatory responses were measured in zebrafish at early life stage. Results showed that DBP exposure caused developmental impairments of heart rate, hatching rate, body length, and mortality in zebrafish embryo. Additionally, the elevated oxidative stress damaged mitochondrial ultrastructure and function and induced oxidative damage to the mtDNA with mutations and instability of replication, transcription, and DNA methylation. The stressed mtDNA leaked into the cytosol and activated the cGAS-STING signaling pathway and inflammation, which were ameliorated by co-treatment with DBP and mitochondrial reactive oxygen species (ROS) scavenger, inhibitors of cGAS or STING. Furthermore, the larval results suggest that DBP-induced mitochondrial toxicity of energy disorder and inflammation were involved in the developmental defects of impaired swimming capability. These results enhance the interpretation of mtDNA stress-mediated health risk to environmental contaminants and contribute to the scrutiny of mitochondrial toxicants.
Keywords: dibutyl phthalate; health risk; mitochondria; mtDNA stress; zebrafish.