p-Coumaric Acid Attenuates Lead Acetate-induced Neurotoxicity in Rats by Improving Behavioral Dysfunction and...

This study evaluated the neuroprotective effects of p-coumaric acid (p-CA) against lead acetate (PbAc)-induced neurotoxicity in rats by focusing on oxidative stress, neuroinflammation, apoptosis, and neuronal plasticity. 35 male rats were randomly assigned to five groups: Control, p-CA (100 mg/kg), PbAc (30 mg/kg), PbAc + p-CA (50 mg/kg), and PbAc + p-CA (100 mg/kg). Treatments were administered orally for 14 days. Behavioral performance was assessed using the open field test (OFT) and elevated plus maze (EPM). Biochemical analyses of brain tissue included the measurement of MDA, GSH, SOD, CAT, and GPx levels. Western blotting was performed to determine the protein expression levels of inflammatory, glial, and synaptic markers, including NF-κB, IL-1β, IL-6, TNF-α, Iba-1, GFAP, PSD-95, and AChE. Quantitative real-time PCR was used to assess the mRNA expression levels of Bax, Bcl-2, Caspase-3, MAP-2, NeuN, and GAP-43. Histological evaluations included hematoxylin-eosin (H&E) staining for neuronal morphology, immunohistochemistry (IHC) for 8-OHdG, GABA, and GFAP, and immunofluorescence (IF) staining for BDNF expression. PbAc exposure caused marked oxidative damage, neuroinflammatory activation, enhanced apoptotic signaling, and impaired neuronal plasticity, accompanied by reduced antioxidant defenses and altered expression of plasticity-related markers. Co-treatment with p-CA significantly ameliorated these biochemical, molecular, and histopathological alterations in a dose-dependent manner. The 100 mg/kg dose of p-CA showed the strongest neuroprotective effect, restoring many parameters close to control levels. Overall, these findings suggest that p-coumaric acid exerts neuroprotective effects against PbAc-induced brain injury by attenuating oxidative stress, neuroinflammation, and apoptosis while supporting neuronal plasticity. Therefore, p-CA may represent a promising natural compound for further investigation in heavy metal-induced neurotoxicity models. However, further studies are required to clarify the upstream molecular signaling pathways involved and to determine whether these protective effects can be maintained under long-term exposure conditions.