Targeting oxidative stress pathways in epilepsy: mechanistic insights into the role of ascorbic acid

Epilepsy, a neurological disease, is linked to oxidative stress generated due to the synchronous firing of neurons during seizures and use of antiseizure medications (ASMs). Among commonly prescribed ASMs, carbamazepine, valproate, and levetiracetam have been implicated in modulating oxidative stress-related signaling pathways, including Nrf2, NF-κB, and MAPK. Ascorbic acid, a potent antioxidant capable of crossing the blood-brain barrier, has emerged as a promising therapeutic candidate. This review examines the molecular mechanisms underlying ASM-associated oxidative stress in clinical, non-kindled/kindled preclinical, as well as non-epilepsy models, and highlights evidence demonstrating the ability of ascorbic acid to attenuate ROS accumulation, enhance endogenous antioxidant defenses, and modulate redox-sensitive signaling pathways implicated in epileptogenesis and ASM-induced toxicity. Collectively, the available evidence suggests that ascorbic acid has the potential to confer neuroprotection and reduce oxidative injury in epilepsy. Insights presented in this review aim to initiate research focusing on ascorbic acid as an adjuvant in epilepsy. Further studies are warranted to clarify its interactions with ASM metabolism, to optimize dosing strategies, and to establish its translational potential as an adjuvant therapy in clinical epilepsy management.