Oxidative stress and ferroptosis involved in 2-ethylhexyl diphenyl phosphate -induced hepatotoxicity in chicken

Organophosphorus flame retardants (OPFRs) are increasingly being used in many industries since brominated flame retardants (BFRs) have been phase-out. However, OPFRs are associated with environmental pollution and animal health risks, especially in the farming industry. Nevertheless, no study has evaluated the toxicity of OPFRs, as a new flame retardant, on avian species. In order to investigate the specific toxic effects of 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure on chickens and the molecular biological mechanisms that cause damage to the organism, the chicken liver has been studied as a potential target organ for toxic effects. In this study, 7-day-old male chickens were treated with different concentrations of EHDPHP to further investigate the toxicity and mechanisms of OPRs on birds. The samples were taken at 14 d, 28 d, and 42 d for analysis. EHDPHP exposure affected the growth and development of chickens. Furthermore, the microstructural and ultrastructural observations clearly reflected the damage caused by EHDPHP exposure to the livers. The levels of the liver tissue asparate aminotransferase (AST) and alanine aminotransferase (ALT) decreased with increasing gavage dose. In contrast, the levels of oxidative stress in chicken liver and the mRNA expression of related factors increased with increasing gavage dose. In addition, EHDPHP exposure increased liver tissue iron content and affected mRNA expression and protein levels of ferroptosis-related factors in livers. Besides, ferroptosis causes inflammation, thus promoting the synthesis and release of inflammatory factors. This research indicates that EHDPHP can damage chicken livers through oxidative stress and ferroptosis.