Soluble neuroprotective antioxidant uric acid analogs ameliorate ischemic brain injury in mice

Haberman, Frank, Tang, Sung-Chun, Arumugam, Thiruma V., Hyun, Dong-Hoon, Yu, Qian-Sheng, Cutler, Roy G., Guo, Zhihong, Holloway, Harold W., Greig, Nigel H. and Mattson, Mark P. (2007) Soluble neuroprotective antioxidant uric acid analogs ameliorate ischemic brain injury in mice. NeuroMolecular Medicine, 9 4: 315-323. doi:10.1007/s12017-007-8010-1


Author Haberman, Frank
Tang, Sung-Chun
Arumugam, Thiruma V.
Hyun, Dong-Hoon
Yu, Qian-Sheng
Cutler, Roy G.
Guo, Zhihong
Holloway, Harold W.
Greig, Nigel H.
Mattson, Mark P.
Title Soluble neuroprotective antioxidant uric acid analogs ameliorate ischemic brain injury in mice
Journal name NeuroMolecular Medicine   Check publisher's open access policy
ISSN 1535-1084
1559-1174
Publication date 2007-12
Sub-type Article (original research)
DOI 10.1007/s12017-007-8010-1
Volume 9
Issue 4
Start page 315
End page 323
Total pages 9
Place of publication Totowa, NJ, United States
Publisher Humana Press
Language eng
Abstract Uric acid is a major antioxidant in the blood of humans that can protect cultured neurons against oxidative and metabolic insults. However, uric acid has a very low solubility which compromises its potential clinical use for neurodegenerative disorders. Here we describe the synthesis, characterization and preclinical development of neuroprotective methyl- and sulfur-containing analogs of uric acid with increased solubility. In vitro and cell culture screening identified 1,7-dimethyluric acid (mUA2) and 6,8-dithiouric acid (sUA2) as two analogs with high antioxidant and neuroprotective activities. When administered intravenously in mice, uric acid analogs mUA2 and sUA2 lessened damage to the brain and improved functional outcome in an ischemia-reperfusion mouse model of stroke. Analogs sUA2 and mUA2 were also effective in reducing damage to the cerebral cortex when administered up to 4 h after stroke onset in a permanent middle cerebral artery occlusion mouse model. These findings suggest a therapeutic potential for soluble analogs of uric acid in the treatment of stroke and related neurodegenerative conditions.
Keyword uric acid analogues
reactive oxygen species
middle cerebral artery occlusion
permanent middle cerebral artery occlusion
oxygen and glucose deprivation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 17 Nov 2009, 12:21:36 EST