Effects of 2-amino-7-phosphonoheptanoic acid, melatonin or NG-nitro-L-arginine on cyanide or N-methyl-D-aspartate-induced neurotoxicity in rat cortical cells

When cortical neuronal cells were exposed to potassium cyanide (0.01, 0.05; 0.1: 0.5, or 1.0 mM;)or N-methyl-D-aspartate (NMDA: 0.005, 0.01, 0.05, 0.1, or 0.2 mM) fbr 24 h at 37 degrees C in a 95% air and 5% CO2 environment, lactate dehydrogenase (LDH) efflux into the extracellular fluid from the cortical cells was significantly increased in a concentration dependent manner and morphological changes were observed. The increased LDH efflux and the morphological changes in cortical cells induced by potassium cyanide or NMDA were blocked by co-exposure to 2-amino-7-phosphonoheptanoic acid (AP7: 1.0 mM), a selective antagonist of the NMDA receptor, melatonin (1.0 mM), a potent hydroxyl and peroxyl radical scavenger, or NG-nitro-L-arginine (1.0 mM), an inhibitor of nitric oxide (NO) synthase. These results suggest that activation of NMDA receptor and NO synthase and/or free radical formation may contribute to the development of neurotoxicity induced by cyanide or NMDA. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.