2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and diacetyldichlorofluorescein

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).

Topics: Animals; Antioxidants; Butylated Hydroxytoluene; Cells, Cultured; Cerebellar Cortex; Chromans; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Synergism; Fluoresceins; Fluorescent Dyes; Iodoacetates; Neuroprotective Agents; Neurotoxins; Oxidative Stress; Piperazines; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate