Fructose-1,6-diphosphate and vitamin C combination increases seizure threshold in chemical kindling models

Abstract

Background: Fructose-1,6-diphosphate (FDP), through its activity in glucose metabolism, has anticonvulsant efficacy whereas vitamin C acts as neuromodulator. Aims and Objectives: To assess the antiepileptic effects of FDP, vitamin C and their combination in intravenous pentylenetetrazole (PTZ) and intracranial carbachol kindling model. Materials and Methods: PTZ kindling was induced by intravenous infusion of PTZ (10 mg/ml; infusion rate: 1 ml/min) to rats. For carbachol kindling, intracranial administration of carbachol (1 µl; 5 µg/ml) was done at well-spaced intervals by introducing maximum three injections a day, and maximum nine administrations until stage 5 epileptic convulsions were produced. The treated group animals received FDP, vitamin C or both, 28 days before the kindling. During kindling, time latency to reach a seizure stage, electroencephalogram (EEG) recording, and frequency of stimulation were recorded. Brain homogenate parameters included measurement of levels of neurotransmitters, glutathione (GSH), and malondialdehyde (MDA). One-way ANOVA was used for determination of a significant difference between the groups. Results: Slowing of seizure progression, increase in seizure threshold and required number of stimuli to reach to stage 5 convulsion was highest with FDP and Vitamin C combination followed by FDP and Vitamin C alone treatment. EEG data during the PTZ infusion indicated ictal epileptiform in disease control group and not in treatment groups. The test drugs either alone or in combination did not alter glutamate and aspartate levels in brain but increased the γ-aminobutyric acid and GSH whereas reduced MDA levels. Conclusion: It can be concluded that both FDP and Vitamin C has beneficial effects in chemical induced kindling and their combination shows synergistic effects.