Efeito anti-inflamatório e neuroprotetor da fucoidana sozinha ou associada ao ácido valpróico no modelo de convulsão induzido por pilocarpina em camundongos

Abstract

Epilepsy is a neurological disorder characterized by a persistent predisposition of the brain to generate and aggravate seizures affecting about 1% of world population. Among the pathophysiological mechanisms involved in the seizure process, neuroinflammation and oxidative stress represent pharmacological targets for novel therapeutic strategies for modifying effects of clinically relevant disease. Currently, the sulfated polysaccharide brown algae (fucoidana), has shown several biological activities such as antioxidant and anti-inflammatory. Thus, the present study aims to assess the anti-inflammatory and neuroprotective fucoidana polysaccharide alone or associated with the valproic acid seizure model in mice induced by pilocarpine. The animals (mice), Swiss, adult, male, (25-30g) were injected in fucoidana (FUCO 7.5, 15 and 30 mg / kg, ip), valproic acid (AVP 100 and 400 mg / kg, ip) , valproic acid + fucoidana (AVP100 FUCO7,5 +) or saline - 0.9% NaCl ip for fourteen days. After 30 minutes the last injection of drug or vehicle was administered methylscopolamine 1 mg / kg, ip, and after 30 minutes, pilocarpine in a dose of 400 mg / kg, ip, and then the animals were subjected to behavioral testing and sacrificed, and the area of ​​the brain (hippocampus) dissected for neurochemical assays for determining the concentrations of inflammatory cytokines (TNF-α and IL-1β) and determination of changes in gene expression (qPCR) related to neuroinflammation and neurotrophic factors. Pretreatment with FUCO for 14 days increased the latency to death of the animals, but there was an increase in seizure latency only in doses of 15 and 30 mg / kg. In AVP400 dose was increased in both the latency and in seizure death, but was not observed any significant effect with the AVP dose of 100 mg / kg. However, FUCO + PVA association seizure latency reduced by 62% and the latency to death by 100% when compared to PILO group. Pilocarpine increased concentration of TNF and IL-1β in the hippocampus of animals and this effect was prevented by pretreatment with fucoidana at all doses for IL-1β and only in smaller doses for TNF. The association of FUCO + PVA caused a decrease by about 69% and 55% in the concentration of IL-1β and TNF, respectively. Pilocarpine increased BDNF mRNA expression, IL-1β and TNF. Our results suggest that fucoidana seems to be an alternative for the treatment of epilepsy when combined with valproic acid as it promotes neuroprotection allowing the reduction of the AVP dose maintained its effects.