Free radicals are involved in methylmethacrylate-induced neurotoxicity in human primary neocortical cell cultures

Methylmethacrylate monomer (MMA), a highly volatile material, has been extensively used for the construction of complete or partial dental prostheses. While previous studies have indicated a variety of complications and untoward side-effects associated with its use, the possible neurotoxicity induced by this monomer has not been addressed. In this study, we have investigated the MMA-produced neuronal injury in human neuron-enriched primary culture. Embryonic brain tissue (8-10 weeks postconception) was used for the primary neuron-enriched culture. Phase-contrast microscopy was used to evaluate morphological changes of cultured neurons. Extracellular concentrations of lactate dehydrogenase (LDH) and nitrite was measured from the culture medium to assess the magnitude of neuronal damage and nitric oxide formation, respectively. Neocortical neurons exposed to the monomer (1/200, V(monomer)/V(glycerol)) for two days resulted in a significant increase in the LDH level but monomer (1/20000, 1/2000, 1/1000, or 1/200; V(monomer)/V(glycerol)) failed to increase the nitrite level. Morphologically, the neurons subjected to monomer treatment exhibited irregular shrunken cell bodies with dystrophic and/or fragmented neurities, or even cell lysis. Moreover, superoxide dismutase plus catalase or vitamin C pretreatment protected against monomer-induced neurotoxicity. Our results suggest that this neurotoxicity can not likely be attributed to the cytotoxic effects of nitric oxide but may be mediated through the toxicity of superoxide and other free radicals. This is the first time, to our knowledge, that neurotoxicity induced by MMA has been demonstrated in human cortical neurons.