Hongal_2025_J.Appl.Toxicol__

Perfluorooctanoic acid is a perfluoroalkyl substance that finds many applications across numerous industrial and household products. Environmental persistence and capacity to accumulate in biological systems are well documented. Increasing evidence links PFOA exposure to neurotoxicity, though its underlying mechanisms remain unclear. The purpose of this research was to assess the neurotoxic implications of PFOA in male Wistar rats by investigating oxidative stress, mitochondrial function, histopathological changes, and glial activation in the hippocampus of the forebrain. Animals received oral doses of PFOA (48 mg/kg and 96 mg/kg) over 30, 60, and 90 days. Brain tissues were examined for lipid peroxidation levels, antioxidant enzyme activity (SOD, CAT, GPx, GST), reduced glutathione levels, mitochondrial membrane potential, and acetylcholinesterase activity. Histological analysis was performed using H&E staining, while glial response was assessed via GFAP immunohistochemistry. The outcomes indicated a marked (p < 0.05), dose- and time-dependent elevation in oxidative stress, evidenced by elevated lipid peroxidation and diminished antioxidant enzyme activity. Mitochondrial dysfunction was confirmed by a disrupted membrane potential, and reduced acetylcholinesterase activity indicated a cholinergic imbalance. Histological analysis showed pronounced neuronal degeneration, cytoplasmic vacuolation, reactive gliosis, and structural disorganization across brain tissues, with detailed microscopic evaluation focused primarily on the hippocampal region along with other affected areas. GFAP upregulation indicated astrogliosis and neuroinflammation. In conclusion, PFOA exposure induces neurotoxicity through oxidative imbalance, mitochondrial disruption, glial activation, and impaired neurotransmission. These findings highlight the neurological risks associated with prolonged PFOA exposure and reinforce the need for regulatory measures and further toxicological evaluation.