Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons.
Novel anti-oxidants based on the buckminsterfullerene molecule were explored as neuroprotective agents in cortical cell cultures exposed to excitotoxic and apoptotic injuries. Two polyhydroxylated C60 derivatives, C60(OH)n, n = 12, and C60(OH)nOm, n = 18-20, m = 3-7 hemiketal groups, demonstrated excellent anti-oxidant capabilities when tested by electron paramagnetic spectroscopy with a spin-trapping agent and a hydroxyl radical-generating system. These water-soluble agents decreased excitotoxic neuronal death following brief exposure to NMDA (by 80%), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; by 65%), or kainate (by 50%). Electrophysiology and tracer 45Ca(2+)-uptake studies verified that buckminsterfullerenois are not NMDA or AMPA/kainate receptor antagonists. Buckminsterfullerenols also reduced neuronal apoptosis induced by serum deprivation. These results support the idea that oxidative stress contributes to both excitotoxic and apoptotic neuronal death, and furthermore suggest that fullerenols represent a novel type of biological anti-oxidant compound.
Dugan
L L
LL
Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gabrielsen
J K
JK
Yu
S P
SP
Lin
T S
TS
Choi
D W
DW
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002244:Carbon / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D016166:Free Radical Scavengers; D037741:Fullerenes; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity; D018384:Oxidative Stress; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013329:Structure-Activity Relationship; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
D000975:Antioxidants; D016895:Culture Media, Serum-Free; D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D037741:Fullerenes; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C107987:buckminsterfullerenol; D016202:N-Methylaspartate; D002244:Carbon; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid