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Robust protective effects of a novel multimodal neuroprotectant oxopropanoyloxy benzoic acid (a salicylic acid/pyruvate ester) in the postischemic brain

Title
Robust protective effects of a novel multimodal neuroprotectant oxopropanoyloxy benzoic acid (a salicylic acid/pyruvate ester) in the postischemic brain
Authors
Kim S.-W.Kim H.J.Shin J.-H.Kim I.-D.Lee J.-E.Han P.-L.Yoon S.-H.Lee J.-K.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2011
Journal Title
Molecular Pharmacology
ISSN
0026-895XJCR Link
Citation
vol. 79, no. 2, pp. 220 - 228
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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 t1/2 = 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-Zn2+-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. Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics Mol Pharmacol.
DOI
10.1124/mol.110.067520
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일반대학원 > 뇌·인지과학과 > Journal papers
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