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

Abstract

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.

Keywords: Anxiety; Cognitive impairment; Neurotoxicity; Phthalates; TLR 4/ NF-κB; Wistar rat.