Multi-omics profiling and biochemical assays reveal the acute toxicity of environmental related concentrations of Di-(2-ethylhexyl) phthalate (DEHP) on the gill of crucian carp (Carassius auratus).

Di-(2-ethylhexyl) phthalate (DEHP) is one of the most extensively utilized plasticizers in the plastic manufacturing process. It is widely used in various fields due to its low cost and excellent effect. Although there is evidence that DEHP is harmful to animal and human health, DEHP-induced gill toxicity in aquatic organisms is inconclusive, and its mechanism has not been fully elucidated. Here, we investigated the effects of DEHP acute exposure on crucian carp gills at environmentally relevant concentrations of 20, 100, and 500 μg/L. Multi-omics profiling and biochemical assays were employed to characterize the potential toxicological mechanisms. The results showed that acute exposure to 100 and 500 μg/L of DEHP leads to oxidative stress in gills, as evidenced by overproduction of reactive oxygen species (ROS), increased antioxidant enzyme activity, and the transformation of glutathione from reduced to oxidized form, resulting in lipid peroxidation. Integrative analysis of transcriptomics and metabolomics indicated that increased purine metabolism was the potential source of increased ROS. Moreover, lipid metabolism disorder, including arachidonic acid metabolism, induces inflammation. Further, DEHP causes the imbalance of the CYP enzyme system in the gill, and DEHP-induced gill toxicity in crucian carp was associated with interference with CYP450 homeostasis. Taken together, this study broadens the molecular understanding of the DEHP-induced gill toxicity in aquatic organisms and provides novel perspectives for assessing the effects of DEHP on target and non-target aquatic organisms in the environment. [Display omitted] • DEHP activates protective responses in the antioxidant system of the gill. • ROS overproduction is related to the increase of purine metabolism. • Dysregulation of lipid metabolism contributes to increased pro-inflammatory effects. • DEHP-induced gill toxicity is associated with disrupting the CYP450 homeostasis. [ABSTRACT FROM AUTHOR]