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 invest igated. Transient exposure to IAA caused a concentration-dependent decrease in cell viability (ED50 = 9.8 mu M). Dizocilpine maleate (MK-801), and 1,2 ,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), failed to prevent IAA toxicity. Certain antioxidant molecules were shown t o be neuroprotective against IAA when combined with MK-801 but were ineffec tive when administered alone. (S)-(-)-Trolox, butylated hydroxytoluene (BHT ), and U-83836E exhibited EC50 values of 78, 5.9, and 0.25 mu M, respective ly, in the presence of 10 mu M MK-801. IAA also induced an increase in intr acellular 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). (C) 2000 Elsevier Science I nc.