title: Antioxidants do not prevent acrylonitrile-induced toxicity.
abstract: Several reports have recently described that acrylonitrile (ACN) toxicity resides in its capacity for inducing oxidative stress. ACN can be conjugated with glutathione (GSH), diminishing its cellular content, or being metabolized to cyanide. In the present report, we determine the effect of ACN on the viability of primary-cultured astrocytes as well as the oxidative damage generated by ACN by measuring GSH levels in primary cultured astrocytes. We also analyzed whether the ACN (2.5mM) toxicity could be avoided by using antioxidants such as taurine (5mM), N-acetylcysteine (20 mM), trolox (100 microM), estradiol (10 microM) and melatonin (100 nM-1mM). In this cell culture model, antioxidants were not able to prevent ACN-induced cell damage, with the exception of NAC, confirming that only GSH seems to play a key role in ACN-derived toxicity. Additionally, we measured different parameters of oxidative stress such as catalase activity, lipid peroxidation and GSH concentration, as indicators of the potential oxidative stress mediated by the toxicity of ACN, after exposure of Wistar rats to a concentration of 200 ppm ACN for 14 days. At the concentration assayed, we did not find any evidence of oxidative damage in the brain of ACN-treated rats.
authors.affiliation: Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Facultad de Medicina de la Universidad de Oviedo. c/Julian Clavería, 33006 Oviedo, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Carrera
authors.forename: I
authors.initials: I
authors.lastname: Antolín
authors.forename: V
authors.initials: V
authors.lastname: Martín
authors.forename: R M
authors.initials: RM
authors.lastname: Sainz
authors.forename: J C
authors.initials: JC
authors.lastname: Mayo
authors.forename: F
authors.initials: F
authors.lastname: Herrera
authors.forename: G
authors.initials: G
authors.lastname: García-Santos
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez
mesh_terms: D000181:Acrylonitrile / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D002374:Catalase; D005978:Glutathione; D000181:Acrylonitrile