Oxidative stress in rat brain during experimental status epilepticus: effect of antioxidants

Abstract

Antioxidants have been proposed as a treatment for diseases of the central nervous system. However, few studies actually studied their effects in the brain. To test central actions of antioxidants, we used the lithium–pilocarpine (Li-Pilo) model of status epilepticus (SE) in the rat in which seizures are accompanied by significant oxidative stress. We used in vivo microdialysis to determine isoprostane levels during SE in real time and brain homogenates for other measures of oxidative stress. Six different antioxidants were tested in acute and preventive experiments (vitamin C, vitamin E, ebselen, resveratrol, n-tert-butyl-α-phenylnitrone and coenzyme Q10). None of the antioxidants had an effect when given acutely during SE. In contrast, when antioxidants were given for 3 days prior to seizure induction, vitamins C and E reduced isoprostane formation by 58% and 65%, respectively. Pretreatment with the other antioxidants was ineffective. In brain homogenates prepared after 90 min of seizures, SE decreased the ratio of reduced vs. oxidized glutathione (GSH/GSSG ratio) from 60.8 to 7.50 and caused a twofold increase of 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels and protein carbonyls. Pretreatment with vitamin C or vitamin E mitigated these effects and increased the GSH/GSSG ratio to 23.9 and 28.3, respectively. Again, the other antioxidants were not effective. We conclude that preventive treatment with vitamin C or vitamin E ameliorates seizure-induced oxidative damage in the brain. Several well-studied antioxidants were inactive, possibly due to limited brain permeability or a lack of chain-breaking antioxidant activity in hydrophilic compounds.

Ascorbic acid mitigates the impact of oxidative stress in a human model of febrile seizure and mesial temporal lobe epilepsy

“…To find a potential mechanism for mitigating oxidative stress in severely diseased-iNSCs, we treated the cells with the antioxidant compound AA (vitamin C) prior to the administration of H 2 O 2 . Previous studies have already demonstrated the protective effects of AA in reducing neuronal damage when administered before the induction of seizures in rats 77 , 78 . In our model, pre-treatment of diseased iNSCs with AA in the presence of oxidative stress led to an up-regulation of proteins associated with cellular protection, such as HSPB1 and p62.…”

Drug Repurposing of Metformin for the Treatment of Haloperidol-Related Behavior Disorders and Oxidative Stress: A Preliminary Study

“…The GSH/GSSG ratio, a key antioxidant measure, was not significantly altered in whole brain tissue homogenate in the current study, possibly due to regional variations. Contrasting findings in studies analyzing specific brain regions like the hippocampus or striatum underscore the importance of localized assessments [73][74][75][76][77]. Also, if, in the case of human samples, the level of GSH in the brain can vary pre-and post-mortem, the same can happen in experimental animals [78].…”

Type 2 diabetes mellitus facilitates status epilepticus in adult rats: Seizure severity, neurodegeneration, and oxidative stress

“…On the other hand, SE promotes an excessive production of free radicals and reactive oxygen species (ROS), which in turn facilitates the establishment of oxidative stress (OS) and contributes to neurodegeneration and epileptogenesis. 9 , 10 , 11 DM also increases ROS generation by affecting different metabolic pathways including glycolysis, glucose auto‐oxidation, sorbitol pathway, protein glycation, and mitochondrial electron transport chain activity, 12 and decreases the body's endogenous antioxidant response, 13 which generates a redox imbalance and triggers OS. This redox imbalance may contribute to DM‐associated brain complications like seizures.…”