Efeitos benéficos do ácido rosmarínico em modelos de atividade epileptiforme in vivo e in vitro induzidos por pilocarpina

Abstract

Epilepsy is a chronic neurological condition marked by the occurrence of epileptic seizures that cause enormous damage to the quality of life of affected patients. Thus, understanding the molecular bases responsible for the development of epilepsy and associated comorbidities is of fundamental importance. Status epilepticus (SE) is a severe type of seizure that is often difficult to control and can lead to death. Rosmarinic acid (RA) has been linked to several biological activities, including anti-oxidant and anti-inflammatory action. In this sense, the present study evaluated the potential beneficial effect of rosmarinic acid in models of epileptiform activity induced by pilocarpine in vivo and in vitro. For this, in the in vivo model, SE was induced in male C57BL/6 mice by low doses of pilocarpine (100mg/kg/i.p.), which received RA (30 mg / kg / vo) 1, 24 and 48 h after the end of SE, we evaluated neuromotor activity by neuroscore and protein levels. carbonyl in the cortex. Using an in vitro model in combination entorhinal cortex-hippocampus of Wistar rats, we evaluated the effects of RA (10 μg / ml) on the release of lactate and fluorescent glucose analogue 2-NBDG after incubation in high potassium aCSF supplemented or not with pilocarpine, we evaluated protein expression by dot blot and western blot. Treatment with RA attenuated neuromotor impairment within 48 hours and decreased levels of carbonyl proteins. In both in vitro models, RA was able to decrease the stimulated lactate release from the slices, while no effect on 2-NBDG uptake was found. In vitro models induced no changes in oxidative stress markers, and AR alone had no effect. The results obtained that AR is a good complementary candidate in the therapy of epilepsy, since it has beneficial effects in an in vitro and in vivo model of epileptiform activity.