title: Arsenic and fluoride induce neural progenitor cell apoptosis.
abstract: The aim of the present study is to determine the effect of inorganic arsenic (As) and its metabolites on the viability of the neural progenitor cell (NPC) line C17.2, in order to evaluate cellular mechanisms involved in As developmental neurotoxicity. Moreover, we analyzed the effects of the coexposure to As and fluoride (F), a situation to which some populations are commonly exposed. Our results show that NPCs are not susceptible to pentavalent As species [arsenate, monomethylarsonic acid, and dimethylarsinic acid] and F alone. However, the trivalent metabolites of arsenate [arsenite, monomethylarsonous acid, and dimethylarsinous acid] are toxic at concentrations below 1 mg/l, and this susceptibility increases when there is coexposure with F (≥ 5 mg/l). Arsenite triggers apoptosis after 24 h of exposure, whereas monomethylarsonous acid produces necrosis at very short times (2 h). Arsenite leads to an increase in intracellular Ca levels and generation of reactive oxygen species, which may cause a decrease in mitochondrial transmembrane potential, release of cytochrome c, and consequent activation of caspases. A slight activation of calpain also takes place, which might favor activation of the mitochondrial pathway or might activate other pathways. The treatment with some antioxidants such as quercetin and α-tocopherol shows only a partial reduction of the cytotoxicity.
authors: Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Apdo. 73, 46100 Burjassot (Valencia), Spain.
authors: R A
authors: RA
authors: Rocha
authors: J V
authors: JV
authors: Gimeno-Alcañiz
authors: R
authors: R
authors: Martín-Ibañez
authors: J M
authors: JM
authors: Canals
authors: D
authors: D
authors: Vélez
authors: V
authors: V
authors: Devesa
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001151:Arsenic / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005459:Fluorides / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D017382:Reactive Oxygen Species; D002154:Calpain; D020169:Caspases; D001151:Arsenic; D005459:Fluorides; D002118:Calcium