title: In vitro toxicity induced by methylmercury on sympathetic neurons is reverted by L-cysteine or glutathione.
abstract: Methylmercury (MeHg) is related to several deleterious effects on the vertebrate nervous system and part of these effects are through interaction with sulfhydryl (-SH) group found in cellular proteins. We decided to characterize the dose-dependent effect of MeHg on the neurotoxicity and the neurite outgrowth induced effects on chick sympathetic neurons dissociated and purified in culture. In this model, MeHg inhibited neurite outgrowth (1-10 microM) and induced cell death (1-10 microM) after 48 h in culture. Since metal toxicity often generates reactive oxygen species, we tested if antioxidant compounds such as glutathione (GSH) or L-cysteine (L-cys) could block the deleterious effects promoted by MeHg. L-methionine, another sulfur-containing amino acid, but without a SH group, was also used in this work. We show that GSH (10-100 microM) and L-cys (100 microM), but not L-methionine (100 microM), fully blocked neurite degeneration and sympathetic neuron cell death in culture.
authors.affiliation: Laboratory Neurochemistry, Program in Neurobiology IBCCF, UFRJ, Rio de Janeiro, Brazil.
authors.forename: Ricardo Augusto
authors.initials: RA
authors.lastname: de Melo Reis
authors.forename: Anderson Manoel
authors.initials: AM
authors.lastname: Herculano
authors.forename: Maurício Castro Cabral
authors.initials: MC
authors.lastname: da Silva
authors.forename: Ronald Marques
authors.initials: RM
authors.lastname: dos Santos
authors.forename: José Luis Martins
authors.initials: JL
authors.lastname: do Nascimento
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003553:Cystine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000633:toxicity*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000166:cytology* / Q000196:embryology; D013997:Time Factors
chemical_list: D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D003553:Cystine; D020932:Nerve Growth Factor; D005978:Glutathione