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Robust Protective Effects of a Novel Multimodal Neuroprotectant Oxopropanoyloxy Benzoic Acid (a Salicylic Acid/Pyruvate Ester) in the Postischemic Brain.
MedLine Citation:
PMID:  21036874     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Cerebral ischemia leads to brain injury via a complex series of pathophysiological events. Therefore, multidrug treatments or multitargeting drug treatments are attractive options in efficiently limiting brain damage. Here, we report a novel multifunctional compound oxopropanoyloxy benzoic acid (OBA-09), a simple ester of pyruvate and salicylic acid. This protective effect was manifested by recoveries from neurological and behavioral deficits. OBA-09 exhibited antioxidative effects in the postischemic brain, which was evidenced by remarkable reduction of lipid peroxidation and 4-hydroxy-2-nonenal staining in OBA-09-administered animals. Reactive oxygen species generation was markedly suppressed in primary cortical cultures under oxygen-glucose deprivation. More interestingly, OBA-09 was capable of scavenging hydroxyl radical in cell-free assays. High-performance liquid chromatography results demonstrated that OBA-09 was hydrolyzed to salicylic acid and pyruvate with t(1/2) = 43 min in serum and 4.2 h in brain parenchyma, indicating that antioxidative function of OBA-09 is executed by itself and also by salicylic acid after the hydrolysis. In addition to antioxidative function, OBA-09 exerts anti-excitotoxic and anti-Zn(2+)-toxic functions, which might be attributed to attenuation of ATP and nicotinamide adenine dinucleotide depletion and to the suppression of nuclear factor-κB activity induction. Together these results indicate that OBA-09 has a potent therapeutic potential as a multimodal neuroprotectant in the postischemic brain and these effects were conferred by OBA-09 itself and subsequently its hydrolyzed products.
Authors:
Seung-Woo Kim; Hyun Ji Kim; Joo-Hyun Shin; Il-Doo Kim; Jung-Eun Lee; Pyung-Lim Han; Sung-Hwa Yoon; Ja-Kyeong Lee
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Publication Detail:
Type:  Journal Article     Date:  2010-10-29
Journal Detail:
Title:  Molecular pharmacology     Volume:  79     ISSN:  1521-0111     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  220-8     Citation Subset:  IM    
Affiliation:
Department of Anatomy, Inha University School of Medicine. 7-241 Shinheung-dong, Jung-Gu, Inchon, 400-712, Republic of Korea. jklee@inha.ac.kr.
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