TBPH-induced lung injury is induced by mitochondrial-derived ds-DNA-mediated inflammatory response.

Due to the ban on the use of traditional brominated flame retardants, new brominated flame retardants, such as Bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), have been developed as alternatives to traditional brominated flame retardants to replace the old ones, and TBPH has been widely used. Therefore, we need to systematically evaluate the toxicological effects of TBPH. In the current work, we analyzed the effects of TBPH on lung. In vivo model, we found that TBPH treatment caused damage to lung tissues through H&E staining, immunohistochemistry, and western-blot analysis. Furthermore, in vitro model, our study found that TBPH treatment led to a decrease in the proliferative capacity of lung cells. Furthermore, TBPH treatment led to inflammatory responses and oxidative stress in lung cells. Molecular mechanism studies showed that under exposure to TBPH, the biological function of mitochondria was disrupted, leading to the release of endogenous ds-DNA from mitochondria into the cytosol. This released ds-DNA acts as a danger signal molecule, effectively activating the cGAS-STING signaling pathway and subsequent inflammatory responses. Further research showed that the disruption of mitochondrial homeostasis by TBPH is closely related to lung injury. The current research findings not only enrich our understanding of the potential toxicological effects of new brominated flame retardants as environmental pollutants, but also provide a research foundation for further understanding TBPH toxicology.