Probing the Effects of N-Acetylglucosamine and Diazepam Combination on Oxidative Stress and Epileptogenesis-Associated Genes in Murine Brain

Abstract

A body of evidence suggests that upregulating O-GlcNAcylation, a reversible post-translational modification of serine and threonine residues on target proteins, is beneficial in neurological diseases. However, this phenomenon is currently underexplored in the pharmacotherapy of epilepsy. Therefore, we aimed to explore the potential effects of combining N-acetylglucosamine (GlcNAc), a precursor for O-GlcNAcylation, and a centrally acting benzodiazepine (diazepam) on oxidative stress, a known driver of epilepsy, and some epileptogenesis-associated genes. Mice (n = 10) were randomly assigned to treatment groups and treated with varied oral doses (100, 200, and 400 mg/kg) of GlcNAc in combination with diazepam (1 mg/kg) for 14 days. Following this, seizure was chemically induced with 70 mg/kg pentylenetetrazol intraperitoneally. Brains of treated mice were excised for antioxidant assays and to determine the expression of genes associated with epileptogenesis: potassium chloride co-transporter (KCC4), interleukin (IL-6), tumour necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF). Our findings suggest that GlcNAc, when concurrently administered with diazepam, prevents oxidative stress and reduces the gene expression of IL-6, a cytokine associated with neuroinflammation and seizures, whilst increasing the gene expression of KCC4, an ion co-transporter that promotes antiepileptogenesis.