Effects of di-(2-ethylhexyl) phthalate on oxidative stress and lipid metabolism in livers of male Xenopus tropicalis

Abstract Di-(2-ethylhexyl) phthalate (DEHP), used as a popular plasticizer to enhance the flexibility of plastics, is a major pollutant in aquatic environments. DEHP poses severe risks to aquatic organisms since it is an endocrine-disrupting compound. To comprehensively evaluate the toxicity of DEHP on the growth and livers of male Xenopus tropicalis(X. tropicalis), sexually mature male X. tropicalis were exposed to environmentally relevant concentrations of DEHP, 0.2, 0.6, 1.8, 5.4 mg/L, for 49 days. The results showed that DEHP had a severe toxic effect on the livers of male X. tropicalis. Histopathological analysis of livers in all the DEHP-exposed groups showed changes in terms of vacuolization, loose cell cords, and an increasing amount of melanin. Large lipid droplets were markedly formed, and there were changes in the mitochondrial morphology upon DEHP exposure. In addition, oxidative stress (excessive ROS and inhibition of antioxidants) was induced through the suppression of biochemical indicators and the downregulation in the mRNA expression of genes (nrf2, cat, sod, gst, and gpx) related to oxidative stress. A reduction in expression of fatty acid metabolism-related gene (pparα) was seen post-DEHP exposure. Thus, our study suggests that the hepatotoxicity induced by DEHP could be attributed to oxidative stress and disordered fatty acid metabolism. In conclusion, long-term exposure to DEHP at environmentally relevant concentrations poses ecological risks to aquatic organisms, which serves as a reminder that the application of DEHP and other plasticizers should be limited.