Protective effects of lamotrigine and vitamin B12 on pentylenetetrazole-induced epileptogenesis in rats

• Published in: Epilepsy & behavior 2021-05, Vol.118, p.107915-107915, Article 107915
• Main Authors: Filiz, Ahmet Kemal, Gumus, Erkan, Karabulut, Sebahattin, Tastemur, Yasar, Taskiran, Ahmet Sevki
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Disease Models, Animal; Epileptogenesis; Hippocampus; Kindling, Neurologic; Lamotrigine - therapeutic use; Male; Neuroinflammation; Neuronal damage; Oxidative Stress; Pentylenetetrazole; Pentylenetetrazole - toxicity; Rats; Vitamin B 12 - pharmacology; Vitamin B12
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2021.107915

•The combination of vitamin B12 and LTG attenuated PTZ-induced epileptogenesis in rats.•Vitamin B12 inhibited cognitive impairment in PTZ-kindled rats.•The combination of vitamin B12 and LTG reduced oxidative stress in PTZ-kindled rats.•The combination of vitamin B12 and LTG showed anti-inflammatory effects in PTZ-kindled rats.•The combination of vitamin B12 and LTG decreased hippocampal neuronal damage. Epileptogenesis is a process that includes molecular and cellular events that foster the establishment of hyperexcitable neuronal networks in the brain. Pentylenetetrazole (PTZ)-induced kindling model in rodents has added new information to the knowledge about the pathogenesis of epilepsy and potential targets of novel antiepileptic agents. Evidence from animal and human studies suggests that oxidative and inflammatory events may play important roles in the initiation and maintaining seizure activities. Vitamin B12 has beneficial effects on the nervous system and presents pleiotropic effects with antioxidant and anti-inflammatory aspects. In the present study, we aimed to test the hypothesis that vitamin B12 and their combination with lamotrigine prevents behavioral deficits, hippocampal damage, oxidation, and proinflammatory state during epileptogenesis. Male rats were subjected to PTZ-induced epileptogenesis and pretreated with vitamin B12 (50 µg/kg) or Lamotrigine (LTG) (25 mg/kg) or B12 (50 µg/kg) + LTG (25 mg/kg). Vitamin B12 and its combination with LTG suppressed epileptogenesis and improved the performance of rats in the passive avoidance test. In addition, Vitamin B12 and its combination with LTG decreased levels of total oxidative status (TOS), oxidative stress index (OSI), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and increased total antioxidant status (TAS) levels in the hippocampus and cerebral cortex. Furthermore, it reduced hippocampal neuronal damage. Current findings support the beneficial actions of vitamin B12 due to its antioxidative and anti-inflammatory properties during the course of disease.