The Effects of G2013 (α-L-guluronic Acid) in a Pentylenetetrazole-induced Kindling Animal Model of Epilepsy

Background: Recent studies have reported observing antioxidant, anti-inflammatory, and anti-aging properties of α-L-Guluronic acid (G2013) in animal and human studies. It has been theorized that the antioxidant and anti-inflammatory properties of G2013 might be beneficial in epilepsy treatment. Objective: We sought to determine G2013's effects on epileptic activity in a kindling-induced animal model. Methods: Thirty rats were randomly divided evenly into three groups (10 rats in each group): 1) the G2013 group, which was treated with daily injections of G2013 for five days prior to the start of the study; during the 14-day study period, the G2013 rats were given single, daily injections of G2013 that preceded single daily injections of pentylenetetrazole (PTZ), a compound used to induce seizures; 2) the Normal group, which only received injections of saline during the 14-day study, with no seizure induction; and 3) the Control group, which received PTZ injections alone (for seizure induction) for the 14-day study period. The latency between seizure stages and duration of seizures in the G2013 and Control groups were measured using a 5-stage seizure severity scale. Brain samples were taken from all three groups and analyzed histopathologically for parenchymal and meningeal inflammatory cell infiltration. Additionally, the brain samples were analyzed to determine gene expression levels of interleukin-1-beta (IL-1β), IL-6, IL-10), tumor necrosis factor (TNF), chemokine (C-C motif) ligand-2 (CCL2), cyclooxygenase-2 (COX-2), and interferon-gamma (IFN-γ). Results: The G2013 group demonstrated lower latency between Stages 2 and 5 seizures, with significantly longer mean duration of Stage 5 seizures, compared to the Control group. No significant differences were observed between the three groups histopathologically nor were there any observed differences in gene expression levels. Conclusion: Our results demonstrated a greater predisposition to PTZ-induced seizures in the rats who received G2013 and PTZ compared to rats who received PTZ alone, suggesting that G2013's epileptogenic property overshadows its anti-inflammatory effects when applied to a kindled animal model of study.

Keywords: Epileptogenesis; G2013; epilepsy; guluronic acid; kindling; pentylenetetrazole.