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The resulting glutamine surplus aggravates glutamine-induced osmotic stress in the cytoplasm, rendering more glutamine available for: (i) its system y + L (Slc7a6)-mediated exchange for extracellular arginine (Arg), which increases the intra-astrocytic accumulation of reactive oxygen-nitrogen species (ROS), (ii) glutamine enter to astrocytic mitochondria, where, hydrolyzed to glutamate and NH 4 + by PAG leads to open mitochondrial permeability transition pore (mPTP), and mitochondrial dysfunction (the Trojan Horse mode of action)