Mitigating effect of ferulic acid on di-(2-ethylhexyl) phthalate-induced neurocognitive dysfunction in male rats with a comprehensive in silico survey

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 397; no. 5; pp. 3493 - 3512
• Main Authors: Khalifa, Mhasen, Fayed, Rabie H., Ahmed, Yasmine H., Sedik, Ahmed A., El-Dydamony, Nehad M., Khalil, Heba M. A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2024; Springer Nature B.V
• Subjects: Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; Anxiety; Anxiety - chemically induced; Anxiety - drug therapy; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain architecture; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Caspase-3; Cognition; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - metabolism; Computer Simulation; Coumaric Acids - pharmacology; Coumaric Acids - therapeutic use; Dietary supplements; Diethylhexyl Phthalate - toxicity; Ferulic acid; Glutathione; Heme oxygenase (decyclizing); Immunohistochemistry; Male; Memory; Molecular Docking Simulation; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Neurotoxicity; Nitric oxide; Nitric-oxide synthase; Oxidative stress; Oxidative Stress - drug effects; Pharmacology/Toxicology; Public health; Rats; Rats, Wistar; Redox properties; Short term memory; Spatial memory; Superoxide dismutase; Oxidative stress; Docking; Neurotoxicity; Cognition; DEHP; Ferulic acid
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-023-02831-9

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.