RESUMO
Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate threatening public health-induced neurotoxicity. This neurotoxicity is associated with behavioral and biochemical deficits in male rats. Our study investigated the neuroprotective effect of ferulic acid (FA) on male rats exposed to DEHP. Thirty-two male Wistar rats were assigned to four groups. Group I control rats received corn oil, group II intoxicated rats received 300 mg/kg of DEHP, group III received 300 mg/kg of DEHP + 50 mg/kg of FA, and group IV received 50 mg/kg of FA, all agents administrated daily per os for 30 days. Anxiety-like behavior, spatial working memory, and recognition memory were assessed. Also, brain oxidative stress biomarkers, including brain malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), brain-derived neurotrophic factor (BDNF) as well as heme oxygenase-1 (HO-1) were measured. Moreover, brain histopathology examinations associated with immunohistochemistry determination of brain caspase-3 were also evaluated. Furthermore, docking simulation was adapted to understand the inhibitory role of FA on caspase-3 and NO synthase. Compared to DEHP-intoxicated rats, FA-treated rats displayed improved cognitive memory associated with a reduced anxious state. Also, the redox state was maintained with increased BNDF levels. These changes were confirmed by restoring the normal architecture of brain tissue and a decrement in the immunohistochemistry caspase-3. In conclusion, FA has potent antioxidant and antiapoptotic properties that confirm the neuroprotective activity of FA, with a possible prospect for its therapeutic capabilities and nutritional supplement value.
RESUMO
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-1ß, 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.