THE EFFECTS OF SORAFENIB, A C-RAF INHIBITOR, IN A KINDLING MODEL OF EPILEPSY

Epilepsy is a neurological disorder in which neuroinflammation plays a key role in seizure pathogenesis. Sorafenib may reduce neuroinflammatory factor expression by inhibiting cRaf-1, suggesting its potential therapeutic relevance in epilepsy. In this study, the effects of sorafenib were investigated in a pentylenetetrazole (PTZ)-induced kindling epilepsy model.
Forty-two Wistar albino male rats (250 ± 25 g, n=7/group) were divided into control, PTZ, PTZ+Sorafenib (10, 20, and 40 mg/kg) and PTZ+VPA (Sodium-Valproate, 150mg/kg). The kindling epilepsy was induced by PTZ (37 mg/kg/day i.p) for 22 days. Sorafenib was administered into rats on alternate days for 44 days. Morris water maze (MWM) and locomotor activity tests were performed. Hippocampal morphological alterations were assessed histopathologically. Oxidative, apoptotic and inflammatory markers in both serum and hippocampal tissue were evaluated by ELISA.
PTZ significantly increased locomotor activity compared with control and PTZ+VPA, which was reduced by sorafenib, with a significant effect observed at 40 mg/kg. PTZ impaired learning in MWM, while sorafenib (20 mg/kg) improved learning performance. PTZ-induced memory deficits were attenuated by VPA and sorafenib, with 10 mg/kg identified as the most efficacious dose. PTZ induced oxidative stress by decreasing hippocampal SOD and increasing MDA levels. Sorafenib attenuated oxidative damage and improved antioxidant status. PTZ also increased caspase-3 and TNF-α, whereas sorafenib reduced apoptotic and inflammatory markers, increased IL-10, and reduced IL-1β and NF-κB. Our results suggest that sorafenib may exert preventive effects in PTZ-induced epilepsy by modulating neuroinflammatory, oxidative, and apoptotic pathways. Supported by Eskişehir Osmangazi University Scientific Research Projects Commission (TDK-2021-1629).