PT  - JOURNAL ARTICLE
AU  - Seung-Woo Kim
AU  - Hyun Ji Kim
AU  - Joo-Hyun Shin
AU  - Il-Doo Kim
AU  - Jung-Eun Lee
AU  - Pyung-Lim Han
AU  - Sung-Hwa Yoon
AU  - Ja-Kyeong Lee
TI  - Robust Protective Effects of a Novel Multimodal Neuroprotectant Oxopropanoyloxy Benzoic Acid (a Salicylic Acid/Pyruvate Ester) in the Postischemic Brain
AID  - 10.1124/mol.110.067520
DP  - 2011 Feb 01
TA  - Molecular Pharmacology
PG  - 220--228
VI  - 79
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/79/2/220.short
4100  - http://molpharm.aspetjournals.org/content/79/2/220.full
SO  - Mol Pharmacol2011 Feb 01; 79
AB  - 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.