Fumaric acid diesters deprive cultured primary astrocytes rapidly of glutathione.

摘要: Fumaric acid esters (FAE) are used for the systemic therapy of psoriasis and now considered treatment autoimmune-based neurological disorders such as multiple sclerosis. Currently, cellular metabolism FAE well mechanisms their therapeutic action poorly understood. Since glutathione (GSH) is involved in detoxification xenobiotics, we analysed consequences an application on content GSH brain cells using astroglia-rich primary cultures model system. Micromolar concentrations dimethyl fumarate (DMF) or diethyl (DEF) lowered a time- concentration-dependent manner. Halfmaximal effects after 60 min incubation were observed 10 μM DMF DEF. In contrast to diesters, monomethyl (MMF), monoethyl (MEF) had be applied mM significantly lower content. During exposure, DEF did not affect cell viability, increase disulfide, nor altered specific activities glucose-6-phosphate dehydrogenase, reductase, lactate dehydrogenase. After removal DEF, cultured astrocytes restored completely within 4 h. These data demonstrate that acute exposure fumaric diesters deprives GSH, most likely by reaction reactive α,β-unsaturated with GSH.