Dose-dependent toxic effects of di-(2-ethylhexyl) phthalate in male rats: Focus on behavioral alterations and inducing TLR4/NF-κB signaling pathway

Di -(2-ethylhexyl) phthalate (DEHP) is a widely used phthalate that possesses a public health concern. Different concentrations of DEHP, including 50, 300, and 750 mg/kg were administrated orally for 28 days in male rats. Body weight and vital organs weight were measured as well as anxiety-like behavior, short and long-term memory were investigated. Brain inflammatory cytokines, including IL-1β, TLR4, NF-κB, TNF-α, and IL1–6 were assessed. Brain caspase-3, neuropeptide-Y (NPY), and brain histopathology were also evaluated. DEHP triggers the release of pro-inflammatory cytokines via inducing the nuclear translocation of the signaling pathway; TLR 4/ NF-κB leads to cognitive impairment and neurodegeneration, which is confirmed by the impaired brain architecture. Also, DEHP upgrades the expression levels of brain caspase-3 and NPY. In conclusion, exposure to high doses of DEHP persuades great toxicity visualized by behavioral, biochemical, and histological impairments when compared to the low doses. •DEHP caused memory impairments associated with anxiety-like behavior.•DEHP caused dose-dependent triggering in the TLR 4/ NF-κB signaling pathway.•DEHP increased the pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α.•Also, it caused neurodegeneration in the brain architecture.