Oxidative stress and modulation of the adenosine system profile: Relationship with epileptogenicity and SUDEP risk
DOI:
https://doi.org/10.47924/neurotarget2025478Keywords:
drug-resistant focal epilepsy, oxidative stress, adenosine, SUDEPAbstract
Purpose. To determine the relationship between oxidative stress and modulation of the adenosine system profile with the epileptogenicity and stratification of sudden unexpected death in epilepsy (SUDEP) risk in temporal and extratemporal drug-resistant focal epilepsy (DRFE).
Methods: Serum samples from 21 patients with EFFR were evaluated. Healthy participants matched for age and sex were also studied. Adenosine and serum concentrations of malonyldialdehyde (MDA) lipid peroxidation, nitric oxide (NOx) production, advanced protein oxidation and glycation products (AGE), and vitamin C were quantified. Multiple regression analysis (automatic, step-by-step) was used to delineate significant markers associated with clinical variables and SUDEP risk. A cluster analysis was performed using validation techniques based on bootstrap.
Results. Adenosine values were markedly greater in patients with DRFE t(33)=1.87, p<0.05. Serum concentrations of oxidative stress products were also significantly higher in patients than in the control group: AGE t(38) =2.577, p<0.01, NOx: t(37)=2.03, p<0.04, MDA: t(38)=3.62, p<0.0008, VitC: t(37)=2.52, p<0.016. There was a proportional directly correlation between the seizure onset age and serum AGE concentrations. (F(5,12) =2.22, p<0.118. The univariate hypothesis test (t-test) showed a trend towards higher adenosine concentrations in patients with high SUDEP risk: 126.81 vs 95.58 t(16)=1.758, p=0. 097.
Conclusions: There are increased profiles of adenosine and oxidative stress toxicity in DRFE patients, with higher prevalence in temporal lobe epilepsy patients. These profiles are associated with epileptogenicity, and are not influenced by anti-seizure medication. In DRFE patients at high SUDEP risk there is a tendency toward higher adenosine concentrations, lending support to the adenosine hypothesis in SUDEP pathophysiology.
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