Interaction of ascorbic acid with the neurotoxic effects of NMDA and sodium nitroprusside.
We have previously shown that ascorbic acid (AA) protects cortical neurons in culture from the toxic effects of NMDA. In the present study, we examined the interactions of AA with toxicity produced by nitric oxide (NO) that is generated from the breakdown of sodium nitroprusside (SNP), and with NMDA toxicity measured 24 h later. AA enhanced SNP toxicity, but it reduced toxicity of NMDA. We propose that these data support a model wherein AA produces neuroprotection by an action at the NMDA receptor, and indirectly with respect to NO. This effect occurs probably by antagonizing Ca2+ influx starting the cascade of biochemical events that lead to the production of NO.
Neuroimaging and Drug Action Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
J A
JA
Bell
C L
CL
Beglan
E D
ED
London
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000196:embryology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005260:Female; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D009599:Nitroprusside / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014665:Vasodilator Agents / Q000633:toxicity*
D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D016202:N-Methylaspartate; D001205:Ascorbic Acid; D002118:Calcium