Estudo dos efeitos da fucoidana sozinha ou em associação com ácido valpróico no modelo de convulsão induzido por pilocarpina em camundongos

Abstract

Epilepsy is one of the most common brain disorders, affecting about 1% of the world population. Seizures can cause neuronal damage, including death of neurons and the pathophysiological mechanisms involved in this process are still unclear. It is known that the seizure activity is associated with biochemical changes in some brain areas and affects several neurotransmitters, carbohydrate metabolism, the second messenger systems and gene expression. Among the biochemical changes involved, there is the increased oxidative stress that can dramatically alter cellular function, being directly related to neuronal death induced by seizure. In this context, exogenous antioxidants may have the ability to reduce oxidative stress and hence neuronal injury, acting also as adjuvants in conventional pharmacological treatment. Fucoidan is a sulfated polysaccharide whose main component is the fucose extracted from brown algae. The literature has shown that fucoidan demonstrates potent antioxidant and anti-inflammatory activities in various experimental models. This study aims to evaluate the effects of fucoidan alone or in combination with valproic acid via antioxidative mechanisms in the pilocarpine model of seizure in mice. The animals (adult male Swiss mice, 25-30g) were treated with fucoidan injection (FUCO 7.5, 15 and 30 mg/kg, i.p.), valproic acid (VPA 100, 200 and 400 mg/kg, i.p.), valproic acid + fucoidan (VPA100 + FUCO7,5) or saline (i.p.) for fourteen days. Thirty minutes after the last injection of drug or vehicle, pilocarpine in the dose of 400mg / kg was administered i.p. Next, the animals were subjected to behavioral testing and then sacrificed and had their brains dissected for further neurochemical analyzes. Pretreatment with FUCO for 14 days in higher doses increased the latency to seizures onset and latency of death. There was no significant effect at a dose of 7.5 mg/kg in these parameters, the same happened to VPA at a dose of 100 mg/kg. However, FUCO+VPA association reduces the latency of seizure onset by 52% and the latency of death by 67%. Increase was observed in MDA concentration in the hippocampus of animals treated with saline+PILO (67%) and this effect was prevented by pretreatment with fucoidan at doses of 15 and 30 mg/kg. The association of FUCO 7.5 mg/kg+VPA 100 mg/kg caused a decrease by about 45% of the MDA concentration compared with control. It was observed a significant increase in the concentration of nitrite/nitrate in the hippocampus of animals treated with saline+PILO (65%). Pretreatment with fucoidan at doses of 7.5, 15 and 30 mg/kg, prevented this increase. The association FUCO+VPA also recovered MDA levels. Pilocarpine caused a reduction in GSH levels, which were recovered by treatment with FUCO+PVA association. The results of this work suggest that fucoidan seems to be an alternative for the treatment of epilepsy when combined with valproic acid as it increases neuroprotection allowing the reduction of VPA doses and therefore, its side effects.