The Effect of β-d-Mannuronic Acid in Animal Model of Epilepsy

Abstract

In the present study, we aimed to evaluate the therapeutic efficacy of β-d-mannuronic acid (M2000) in a rat model of epilepsy. Pentylenetetrazole (PTZ)-induced kindling model was applied in 30 Wistar rats divided into 3 groups through a total of 14 injections, while the rats in the drug-tested group were treated with M2000. Animals were observed for various seizure stages, delay that the rats developed in stages 2 and 5, and the duration of stage 5 seizures. After the last injection, the animals were euthanized and analysis was conducted in the brain for the various gene expression profiles along with histopathology assessments. Pretreatment of animals with M2000 has significantly accelerated epilepsy outcomes promptly following the first PTZ injection (mean ± standard deviation [SD] for seizure stage in the M2000 group was 3.12 ± 1.55 vs 0.75 ± 1.03 for control, P = 0.004). Notably, the mean (±SD) on the latency phase 2 and 5 seizures was lower in the M2000 group compared with control group (79.4 ± 30.7 vs 133.0 ± 38.4, P < 0.001, and 126.1 ± 27.6 vs 233.3 ± 142.8, P = 0.001, respectively). Finally, the mean (±SD) duration of phase 5 seizures was significantly higher in the M2000 pretreated group compared with control rats (344 ± 54 vs 197 ± 94, P < 0.001). Histological findings on the hippocampus showed no significant differences among all groups. Elevated expression level of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ, and cyclooxygenase-2 was seen in the PTZ-induced kindling group. An elevated expression level of IL-10 was observed in the brains of rats in the M2000 treat group. Our results indicated that rats pretreated with M2000 were predisposed to epilepsy promptly after the first PTZ injection.