RESUMO
The antiperoxidative properties of alpha-mangostin, a xanthone isolated from mangosteen fruit, were tested for the first time in nerve tissue exposed to different toxic insults. Two reliable biological preparations (rat brain homogenates and synaptosomal P2 fractions) were exposed to the toxic actions of a free radical generator (ferrous sulfate), an excitotoxic agent (quinolinate), and a mitochondrial toxin (3-nitropropionate). alpha-Mangostin decreased the lipoperoxidative action of FeSO(4) in both preparations in a concentration-dependent manner, and completely abolished the peroxidative effects of quinolinate, 3-nitropropionate and FeSO(4) + quinolinate at all concentrations tested. Interestingly, when tested alone in brain homogenates, alpha-mangostin significantly decreased the lipoperoxidation even below basal levels. alpha-Mangostin also prevented the decreased reductant capacity of mitochondria in synaptosomal fractions. Our results suggest that alpha-mangostin exerts a robust antiperoxidative effect in brain tissue preparations probably through its properties as a free radical scavenger. In light of these findings, this antioxidant should be tested in other neurotoxic models involving oxidative stress.
Assuntos
Antioxidantes/farmacologia , Encéfalo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Xantonas/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/ultraestrutura , Relação Dose-Resposta a Droga , Compostos Ferrosos/antagonistas & inibidores , Compostos Ferrosos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Nitrocompostos/antagonistas & inibidores , Nitrocompostos/farmacologia , Propionatos/antagonistas & inibidores , Propionatos/farmacologia , Ácido Quinolínico/antagonistas & inibidores , Ácido Quinolínico/farmacologia , Ratos , Ratos Wistar , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Sinaptossomos/ultraestrutura , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Alpha-mangostin is a xanthone with antioxidant properties isolated from mangosteen fruit. The reactive oxygen species (ROS) scavenging capacity and the potential protective effect of alpha-mangostin against the mitochondrial toxin 3-nitropropionic acid (3-NP) in primary cultures of cerebellar granule neurons (CGNs) were studied in the present work. It was found that alpha-mangostin was able to scavenge in a concentration-dependent way singlet oxygen, superoxide anion and peroxynitrite anion. In contrast, alpha-mangostin was unable to scavenge hydroxyl radicals and hydrogen peroxide. Furthermore, alpha-mangostin was able to ameliorate in a concentration-dependent way the neuronal death induced by 3-NP. This protective effect was associated with an amelioration of 3-NP-induced reactive oxygen species formation. It is concluded that alpha-mangostin is able to scavenge directly several ROS and has a neuroprotective effect against 3-NP in primary cultures of CGNs, which is associated with its ability to ameliorate 3-NP-induced ROS production.