Neuroprotective effects of creatine administration against NMDA and malonate toxicity.
We examined whether creatine administration could exert neuroprotective effects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid. Oral administration of 1% creatine significantly attenuated striatal excitotoxic lesions produced by NMDA, but had no effect on lesions produced by AMPA or kainic acid. Both creatine and nicotinamide can exert significant protective effects against malonate-induced striatal lesions. We, therefore, examined whether nicotinamide could exert additive neuroprotective effects with creatine against malonate-induced lesions. Nicotinamide with creatine produced significantly better neuroprotection than creatine alone against malonate-induced lesions. Creatine can, therefore, produce significant neuroprotective effects against NMDA mediated excitotoxic lesions in vivo and the combination of nicotinamide with creatine exerts additive neuroprotective effects.
Malcon
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C
Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Kaddurah-Daouk
R
R
Beal
M F
MF
D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D003401:Creatine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008314:Malonates / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008314:Malonates; D018696:Neuroprotective Agents; D009536:Niacinamide; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C030290:malonic acid; D003401:Creatine; D007608:Kainic Acid; D002118:Calcium