Estudo dos efeitos neuroprotetores do extrato hidroalcoolico de própolis vermelha em modelos de convulsão induzidos quimicamente em camundongos

Abstract

Epilepsy is a neurological disorder that affects approximately 1% of the world population and can lead to cognitive deficit, neuronal dysfunction, behavioral and social problems. This disease is capable of generating recurrent seizures, where currently 30 to 40% of all patients do not respond to any type of therapy. Previous studies have shown that the seizure is positively related to inflammatory and pro-oxidant pathways, which can be both the cause and the consequence. Red propolis from hives located on the stems of mangrove shrubs located in Northeastern Brazil is rich in flavonoids with proven anti-inflammatory and antioxidant activities. Previous research has proven the neuroprotective activity of the hydroalcoholic extract of red propolis (EHPV). The objective of this work was to study the neuroprotective and anticonvulsant potential of EHPV in mice submitted to the seizure models induced by pilocarpine (PILO) and pentylenetetrazole (PTZ). Male Swiss mice (20-29g) were pre-treated with EHPV (10 and 100 mg / kg, ip., N = 8) in repeated dose treatment for 7 days. Half an hour after the last dose of EHPV, seizures were induced in the animals by administering PILO 400 mg / kg, i.p. or PTZ 85 mg / kg i.p. In the behavioral analysis, the parameters were evaluated: first seizure latency, interval between the first seizure and death and death latency. After the tests, the brain areas: prefrontal cortex, hippocampus and striatum were dissected. Oxidative stress parameters were measured: malondialdehyde, nitrite and reduced glutathione (GSH) and IL-1β was measured. The project was approved by the Animal Use Ethics Committee (CEUA) of the Federal University of Ceará (UFC) filed under CEUA nº 1057050220. The results showed that the EHPV in the two tested doses, 10 and 100 mg / kg was able to significantly increase behavioral parameters: first seizure latency, interval between first seizure and death and death latency in animals submitted to the two seizure models (PTZ and PILO) evaluated in this study. In addition, EHPV 10 and 100 mg / kg, significantly reduced lipid peroxidation and nitrite levels, as well as being able to considerably increase the levels of reduced glutathione in the three brain areas studied, in animals submitted to seizure models. induced by PTZ and PILO. In assessing anti-inflammatory activity, EHPV considerably decreased the levels of IL-1β in the hippocampus of animals that received injections of seizure-inducing agents, PTZ and PILO. These data are expected to expand information on the role of inflammation and oxidative stress in seizures and on the anticonvulsant and neuroprotective role of EHPV. The results obtained in this study may open perspectives for the development of new and effective pharmacotherapeutic approaches for epilepsy and about possible mechanisms of action of EHPV and its constituents.