title: Characterization of iodoacetate-mediated neurotoxicity in vitro using primary cultures of rat cerebellar granule cells.
abstract: The neuroprotective efficacy of antioxidant molecules against iodoacetate (IAA) neurotoxicity in rat cerebellar granule cell (CGC) cultures was investigated. Transient exposure to IAA caused a concentration-dependent decrease in cell viability (ED50 = 9.8 microM). Dizocilpine maleate (MK-801), and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide (NBQX), failed to prevent IAA toxicity. Certain antioxidant molecules were shown to be neuroprotective against IAA when combined with MK-801 but were ineffective when administered alone. (S)-(-)-Trolox, butylated hydroxytoluene (BHT), and U-83836E exhibited EC50 values of 78, 5.9, and 0.25 microM, respectively, in the presence of 10 microM MK-801. IAA also induced an increase in intracellular oxidative stress, which was quenched by the antioxidants (in the presence of MK-801) in cultures loaded with the oxidant sensitive dye 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA).
authors.affiliation: Cerebrus Ltd., Winnersh, Wokingham, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Malcolm
authors.forename: K R
authors.initials: KR
authors.lastname: Benwell
authors.forename: H
authors.initials: H
authors.lastname: Lamb
authors.forename: D
authors.initials: D
authors.lastname: Bebbington
authors.forename: R H
authors.initials: RH
authors.lastname: Porter
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D007461:Iodoacetates / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D002839:Chromans; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007461:Iodoacetates; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C066382:U 78517F; D002084:Butylated Hydroxytoluene; C029569:diacetyldichlorofluorescein; D016291:Dizocilpine Maleate; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid