Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer which is mainly used as a kind of plastic additive to increase the flexibility of plastic products. Given the widespread use of plastic products, DEHP, as a ubiquitous artificial pollutant, are widely present in the environment. In addition, DEHP could cause biological damage in various organs through oxidative stress. Nano-Selenium, a novel form of selenium, has a wide variety of biomedical applications as an antioxidant, anticancer and anti-inflammatory agent. Nevertheless, researches on the toxicity of DEHP in chicken hepatocyte lines is insufficient. In particular, researches on the interaction between DEHP and nano-selenium is insufficient in chicken cell. Therefore, the innovation of this study is to explore the theoretical mechanism of DEHP toxicity in hepatocytes and the antagonistic effect of nano-selenium on a series of damage in chicken hepatocytes caused by DEHP. Our results showed that, after DEHP exposure, oxidative stress levels in hepatocytes increased, and the mRNA and protein levels of apoptosis-related genes p53, Capsase9, Caspase3 and Bax increased significantly except Bcl-2. The protein levels of apoptosis markers cleaved-Caspase9 and cleaved-Caspase3 also increased significantly. Moreover, the result of TUNEL assay also showed that the level of apoptotic cells increased after DEHP exposure. Meanwhile, the mRNA and protein levels of PI3K, AKT and p-AKT decreased. Therefore, DEHP is able to enhance the degree of oxidative damage and apoptosis of chicken liver cells. Nevertheless, the addition of nano-selenium can reverse the above changes. Experimental results revealed that nano-selenium antagonizes the toxic effects of DEHP via the PI3K/AKT pathway.

The widespread use of plastics has led to a substantial increase in plastic waste, resulting in the dissemination of plastic debris throughout ecosystems and posing significant threats to biota. Bis(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, enhances plastic flexibility but may also exert subtle toxic effects. This study aimed to investigate the potential toxicological impacts and underlying mechanisms of microplastics (MPs), di-(2-ethylhexyl) phthalate (DEHP), and their combined exposure (MPs + DEHP) on oxidative stress, apoptotic damage, transcriptomic alterations, and metabolic disturbances in mice. The results demonstrated that exposure to MPs, DEHP, and MPs + DEHP impaired the antioxidant defense system and reduced overall antioxidant capacity. Concurrently, all three exposure conditions significantly increased biochemical markers, particularly those associated with liver dysfunction, prompting further analysis of hepatic tissues. Histopathological examination revealed apoptotic damage in hepatocytes. Integrated transcriptomic and metabolomic analyses indicated that exposure to MPs, DEHP, and MPs + DEHP disrupted carbohydrate, amino acid, and lipid metabolism, induced the expression of genes related to hepatocarcinogenesis, and impaired purine metabolism. Moreover, MP and DEHP exposure aggravated hepatic apoptosis and inflammatory responses via activation of the PI3K/AKT signaling pathway, thereby eliciting notable biotoxic effects. These findings provide new scientific evidence regarding the individual and combined toxicological effects of MPs and the plastic additive DEHP on living organisms.