Characterization of iodoacetate-mediated neurotoxicity in vitro using primary cultures of rat cerebellar granule cells.
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).
Malcolm
C S
CS
Cerebrus Ltd., Winnersh, Wokingham, UK.
Benwell
K R
KR
Lamb
H
H
Bebbington
D
D
Porter
R H
RH
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*
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