Protective effect of edaravone against manganese-induced toxicity in cultured rat astrocytes.

Abstract

Manganese (Mn), a trace metal, is essential for maintaining the normal regulation of many biochemical and cellular processes. However, accumulation of Mn due to excessive environmental exposure leads to neurological impairment, referred to as manganism. Edaravone (EDA) is a potent free radical scavenger that has been clinically shown to reduce the neuronal injury after cerebral ischemia. In the present study, we aimed to examine the protective effects of EDA against Mn toxicity in astrocyte cultures. Astrocyte cultures were prepared from cerebral cortices of newborn Sprague-Dawley rats. The experiments were performed between 16 and 18 days of cultures. Astrocytes were treated in DMEM medium containing Mn (1-1000μM) for 24h to test Mn toxicity. In order to assess the effect of EDA, cells were pre-treated with different doses of EDA (10, 100 and 1000μM) 6h before Mn treatment. Cell viability (MTT), apoptotic cell death (Hoechst test) and lipid peroxide levels were evaluated in cultures. Our results showed that Mn significantly and dose-dependently reduced cell viability in astrocyte cultures. The apoptotic cell death and lipid peroxides were significantly higher in Mn treated cultures. Treatment of astrocytes with EDA successfully suppressed oxidative stress and cell death due to Mn exposure. The findings of the present study suggest that Mn cytotoxicity is mainly associated with ROS generation and apoptotic cell death. Besides, EDA may have beneficial effects against Mn toxicity. However, further studies are needed to elucidate the molecular mechanisms underlying protective effect of EDA.