Ketogenic Diet Mitigates Hippocampal CA3 Degeneration in Male Wistar Rats with PTZ-Induced Kindling Seizures

Abstract

The ketogenic diet (KD) is a high-fat, low-carb diet used to treat neurological illnesses, inborn metabolic abnormalities, and pharmaco-refractory epilepsy. The pathophysiology of KD is unknown. The PTZ-kindling (PTZK) 35 mg/kg every other day model was utilised to study KDs' effects on epilepsy. Thirty adult male Wistar rats were divided into six groups of five rats each. Group 1, control (standard feed); Group 2 PTZK; Group 3 PTZK + standard feed and levetiracetam (10 mg/kg); Group 4, PTZK + palm-kernel-oil-KD; Group 5, PTZK + castor-oil-KD; and Group 6, PTZK + olive-oil-KD. To promote kindling, the PTZ i.p. dose was increased progressively (5 mg/kg) after the fourth injection. Animals were fed their diets for 14 days after 21 days of Kindling induction. Ketone bodies' (KB) and levetiracetam's binding-affinity to free fatty acid receptor 2 and 3 (FFAR2 and FFAR3) were determined by molecular docking in silico. To assess memory, Y-maze was used. The Unbiased designed-based stereological approach assessed hippocampi CA3 neurons, and the Feulgen reaction examined DNA-fragmentation. The KB has a stronger binding-affinity to FFAR2 and FFAR3 than levetiracetam in silico analysis. The KD groups (4, 5, and 6) had a seizure score of 3 compared to the PTZK group (2)'s 4. KD (4) has reversed memory loss. The PTZK group (2) had fewer pyramidal layer CA3 neurons and higher DNA-breakage than the KD groups (4, 5, and 6). The study shows that KB binding to FRR2 and FFR3 may improve seizure resistance, short-term memory, and neurodegenerative safety.