Interaction of methacrylonitrile with glutathione

The interaction of methacrylonitrile (MeAN) with glutathione (GSH) was evaluated in aqueous solution and its in vivo potential to deplete GSH in male Sprague Dawley rats at the 0.5 LD50 dose of 100 mg MeAN/Kg body weight was investigated. Addition of MeAN (0-40 mM) to a solution of 0.3 mM GSH in 2 mM EDTA, pH 7.4, resulted in a time and concentration dependent depletion of GSH determined as nonprotein sulfhydryl. Thin layer chromatography analysis of incubation mixtures of MeAN with GSH and cysteine showed the appearance of distinct spots representing the adducts S-cyanopropyl GSH and S-cyanopropyl cysteine. Oral administration of MeAN to the rats resulted in significant depletion of GSH in the liver, kidney, heart, lung, brain and spleen. The maximum GSH depletion was noticed in the liver (approximately 39% of control) and in other organs it ranged between 26-34% of control. It is likely that the toxicity of MeAN may be related to in vivo GSH depletion.