Mitochondrial DNA Stress-Mediated Health Risk to Dibutyl Phthalate Contamination on Zebrafish (Danio rerio) at Early Life Stage

Abstract

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.

Moldable Plastics (Polycaprolactone) can be Acutely Toxic to Developing Zebrafish and Activate Nuclear Receptors in Mammalian Cells

“…Zebrafish are a widely used model organism in chemical and material toxicology because of their rapid development, ease of use, and well-documented phenotypes and responses to chemical toxicants (e.g., polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and bisphenol A). , Additionally, fish embryos can be more susceptible to toxicants during early development, thus providing greater sensitivity to the effects of any leached chemicals from the moldable plastic. Exposure to plastics and their associated chemicals has often resulted in sublethal effects reflected by changes in gene expression, metabolic activity, and behavior. − Only in a few instances have plastic items been acutely toxic to zebrafish embryos. In these cases, toxicity has been attributed to the release of a residual, nonintentionally added substance (e.g., acrylate monomer or surfactant). , …”