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• W2589680782 abstract "Abstract Ethyl pyruvate (EP) is a simple aliphatic ester of pyruvic acid and has been shown to have robust neuroprotective effects via its anti-inflammatory, anti-oxidative, and anti-apoptotic functions. In an effort to develop novel EP derivatives with greater protective potencies than EP, we generated four EP isosteres, among them the neuroprotective potency of N,N-diethyl-2-oxopropanamide (DEOPA), in which the ethoxy group of EP was replaced with diethylamine, was far greater than that of EP. When DEOPA was administered intravenously (5 mg/kg) to rat middle cerebral artery occlusion (MCAO) model at 6 hrs post-surgery, it suppressed infarct formation, ameliorated neurological and sensory/motor deficits, and inhibited microglial activation and neutrophil infiltrations in the postischemic brain more effectively than EP. In particular, DEOPA markedly suppressed LPS-induced nitrite production and cytokine/chemokine inductions in microglia, neutrophils, and endothelial cells and these effects are attributable to inhibition of the activity of NF-κB by suppressing IκB-α degradation and p65 to DNA binding. In addition, DEOPA suppressed NMDA-induced neuronal cell death in primary cortical neuron cultures by NAD replenishment and suppression of NF-κB activity. Together, these results indicate DEOPA has multi-modal protective effects against ischemic brain damage targeting numerous cell types in the brain and also against other inflammation-related diseases." @default.
• W2589680782 created "2017-03-03" @default.
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• W2589680782 date "2017-02-21" @default.
• W2589680782 modified "2023-10-16" @default.
• W2589680782 title "Anti-inflammatory and anti-excitoxic effects of diethyl oxopropanamide, an ethyl pyruvate bioisoster, exert robust neuroprotective effects in the postischemic brain" @default.
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• W2589680782 doi "https://doi.org/10.1038/srep42891" @default.
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