The novel neuroprotective action of sulfasalazine through blockade of NMDA receptors.
Sulfasalazine is widely used to treat inflammatory diseases. Besides anti-inflammatory actions such as blockade of nuclear factor-kappaB and cyclooxygenases, we found that 30 to 1000 micro M sulfasalazine dose dependently blocked N-methyl-D-aspartate receptor-mediated excitotoxicity without intervening kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid neurotoxicity. The neuroprotective effects of sulfasalazine were attributable to prevention of Ca(2+) influx and accumulation through N-methyl-D-aspartate receptors as a low-affinity antagonist. The systemic administration of sulfasalazine reduced neuronal death following transient cerebral and retinal ischemia in adult rat. The present findings suggest that the neuroprotective action of sulfasalazine can be therapeutically applied to halt devastating neuronal death following hypoxic ischemia, trauma, and neurodegenerative diseases.
Ryu
Bo Rum
BR
Department of Neuroscience and Pharmacology, Center for the Interventional Therapy of Stroke and Alzheimer's Disease (CITSAD), Ajou University School of Medicine, Suwon, Kyunggi-do, Korea.
Lee
Young Ae
YA
Won
Seok Joon
SJ
Noh
Ji-Hyun
JH
Chang
Su-Youne
SY
Chung
Jun-Mo
JM
Choi
Jun Sub
JS
Joo
Choun Ki
CK
Yoon
Sung Hwa
SH
Gwag
Byoung Joo
BJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D007511:Ischemia / Q000517:prevention & control; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012164:Retinal Diseases / Q000517:prevention & control; D012460:Sulfasalazine / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D007527:Isoenzymes; D016328:NF-kappa B; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D012460:Sulfasalazine; D016202:N-Methylaspartate; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium