DEHP (Di(2-ethylhexyl) phthalate) is the most abundant phthalate component detected in environmental samples as it is widely used in the manufacturing of children's toys, medical devices and furniture. Due to its wide prevalence and propensity to accumulate in the food chain, significant concerns have risen about the safety profile of DEHP. Here, we used a zebrafish model to investigate the toxicity mechanisms of DEHP. Our results indicated that exposure to DEHP altered the ROS content in zebrafish spleen and inhibited the activities of antioxidant enzymes SOD and CAT, detoxification enzyme GSH-Px and induced histopathological damage. In addition, elucidated the mechanism of DEHP significantly promoted apoptosis and caused damage in spleen cells through the bax/bcl-2 pathway. Further genetic testing demonstrated significant alterations in mitochondrial biogenesis, fission, and fusion-related genes and suggested potential mechanistic pathways, including GM10532/m6A/FIS1 axis, the STAT3/POA1 axis, and the NFR1/TFAM axis. Serological and genomic analysis indicated that DEHP exposure activated the C3 complement cascade immune pathway and interfered with innate immune function. IBRv2 analysis proposes that innate immunity may serve as a signal indicator of early toxic responses to DEHP pollutants. This study provided comprehensive cellular and genetic data for DEHP toxicity studies and emphasized the need for future management and remediation of DEHP contamination. It also provides data to specifically support the health risk assessments of DEHP, as well as contributing to broader health and environmental research.
Keywords: Apoptosis; Di(2-ethylhexyl) phthalate; Health risk; Innate immunity interference; Mitochondrial function.
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