Ethyl pyruvate: a novel anti‐inflammatory agent

Fink, Mitchell P.

doi:10.1111/j.1365-2796.2007.01789.x

Cited by 154 publications

(119 citation statements)

References 86 publications

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“…Neuroprotective effects of EP have been studied extensively using animal models. The studies by Fink [1,13] emphasized EP's role as a radical scavenger, while the studies by Litt and his collaborators emphasized rescue from intracellular energy failure [16]. However, EP's effects of radical scavenging and metabolic improvement are neither exclusive nor independent.…”

Section: Discussionmentioning

confidence: 97%

“…However, studies in human patients, while showing no harm, have so far failed to reveal distinct therapeutic benefits [13].…”

Section: Discussionmentioning

confidence: 99%

“…Ethyl pyruvate (ethyl 2-oxopropanoate; CAS Registry Number: 617- , by contrast, is a stable and lipophilic derivative of pyruvate [1,12,13]. Since ethyl pyruvate (EP) is electrically neutral, it easily enters cells, apparently without the help of monocarboxylate transporters (MCT) [14] which are needed by pyruvate for intracellular entry [15].…”

Section: Introductionmentioning

confidence: 96%

“…At least three mechanisms might be responsible for exogenous EP's superiority to pyruvate in the early period after ischemia and oxidative stress: the absence of parapyruvate poisoning, better radical scavenging, and better metabolic function from EP being a fuel that boosts TCA cycle metabolism [16]. Moreover, approximately 3-6 h after ischemia or oxidative stress there is an important fourth mechanism: anti-inflammatory actions by EP but not by pyruvate [1,13,[18][19][20][21].…”

Section: Introductionmentioning

confidence: 98%

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Neuroprotective Effects of Ethyl Pyruvate on Brain Energy Metabolism after Ischemia-Reperfusion Injury: A 31P-Nuclear Magnetic Resonance Study

et al. 2008

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The neuroprotective effects of ethyl pyruvate (EP), a stable derivative of pyruvate, on energy metabolism of rat brain exposed to ischemia-reperfusion stress were investigated by (31)P-nuclear magnetic resonance ((31)P-NMR) spectroscopy. Recovery level of phosphocreatine after ischemia was significantly greater when superfused with artificial cerebrospinal fluid (ACSF) with 2 mM EP than when superfused with ACSF without EP. EP was neuroprotective against ischemia only when administered before the ischemic exposure. Intracellular pH during ischemia was less acidic when superfused ahead of time with EP. EP did not show neuroprotective effects in neuron-rich slices pretreated with 100 microM fluorocitrate, a selective glial poison. It was suggested that both the administration of EP before ischemic exposure and the presence of astrocytes are required for EP to exert neuroprotective effects. We suggest the potential involvement of multiple mechanisms of action, such as less acidic intracellular pH, glial production of lactate, and radical scavenging ability.

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Section: Discussionmentioning

confidence: 97%

“…However, studies in human patients, while showing no harm, have so far failed to reveal distinct therapeutic benefits [13].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Neuroprotective Effects of Ethyl Pyruvate on Brain Energy Metabolism after Ischemia-Reperfusion Injury: A 31P-Nuclear Magnetic Resonance Study

et al. 2008

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“…Ethyl pyruvate, a simple aliphatic ester of pyruvic acid, has been shown to act as an anti-inflammatory molecule and to improve the outcome in sepsis, hemorrhagic shock, acute respiratory distress syndrome, and acute pancreatitis (Fink 2007). Ethyl pyruvate also inhibits dopamine-induced apoptosis in PC12 cells by reducing ROS production and causing p53 upregulation and loss of mitochondria membrane potential (Wang et al 2005).…”

mentioning

confidence: 98%

Combination Treatment with Ethyl Pyruvate and Aspirin Enhances Neuroprotection in the Postischemic Brain

et al. 2009

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Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, has been shown to act as an anti-inflammatory molecule in various pathological conditions, which include sepsis or hemorrhagic shock. Recently, we showed that ethyl pyruvate has a neuroprotective effect in the postischemic brain and also in KA-induced pathogenesis in the brain. In this study, we examined whether aspirin augments neuroprotective effect of ethyl pyruvate in transient focal ischemia model by complementing the neuroprotective effects of ethyl pyruvate. Although, most of neuroprotective effect of aspirin has been attributed to the anti-platelet action, aspirin also has direct neuroprotective effects, including NF-kappaB inhibition. Ethyl pyruvate dose-dependently suppressed infarct formation in the postischemic brain, wherein intravenous administration of 5 mg/kg ethyl pyruvate 30 min after the occlusion reduced infarct volume to 34.5 +/- 15.5% (n = 6, P < 0.01) of that of the untreated control. In combination with aspirin (5 mg/kg, i.v.), the neuroprotective effect was enhanced, resulting in 16.0 +/- 5.9% (n = 6, P < 0.01) infarct volume. The time window for synergistic neuroprotection by ethyl pyruvate and aspirin extended to 9 h post-MCAO. The synergistic reduction in infarct volume was accompanied by suppression of the clinical manifestations associated with cerebral ischemia including motor impairment and neurological deficits. Inflammatory processes including microglial activation and proinflammatory cytokine expression were notably suppressed by the combination treatment in the postischemic brain and in primary microglia cultures, wherein ethyl pyruvate and aspirin modulate NF-kappaB signaling differentially. Aspirin interferes with IkappaB phosphorylation and degradation in the cytoplasm, possibly by specifically inhibiting IkappaB kinase-beta, whereas, the effect of ethyl pyruvate seems to occur in the nucleus, where it may interfere with the binding of NF-kappaB to responsive promoter elements in the target genes. Similar enhancement in neuroprotective effect was also observed in primary cortical cultures after NMDA or Zn(2+) treatment or oxygen-glucose deprivation. Together, these results indicate that combination treatment of ethyl pyruvate and aspirin affords synergistic neuroprotection in the postischemic brain with a wide therapeutic window, in part via differential modulation of the NF-kappaB signaling pathway.

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Ethyl Lactate Ameliorates Hepatic Steatosis and Acute‐on‐Chronic Liver Injury in Alcohol‐Associated Liver Disease by Inducing Fibroblast Growth Factor 21

Jiang,

Wei,

Shen

et al. 2024

Advanced Science

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Aberrant upregulation of hepatic lipogenesis induced by chronic and excessive alcohol consumption is a critical driver of the progression of alcohol‐associated liver disease (ALD), however, no effective approaches inhibiting lipogenesis are currently available for treating ALD patients. Moreover, little is known about whether and how nonethanol ingredients in alcoholic beverages regulate the pathogenesis of ALD. Here the discovery of a small molecule that activates the production and secretion of fibroblast growth factor 21 (FGF21) is reported. It is shown that the activator ethyl lactate, a nonethanol ingredient found in distilled liquors, ameliorates alcoholic hepatosteatosis, inflammation and acute‐on‐chronic liver injury by stimulating FGF21. In response to chronic‐plus‐binge ethanol feeding or fasting, ethyl lactate mimics lipogenesis lowering effects by stimulating FGF21 production through the NAD+‐dependent deacetylase sirtuin 1 (SIRT1) signaling pathway. These ethyl lactate‐mediated beneficial effects are abolished by inhibition of SIRT1 through injection of EX527. Importantly, FGF21 deficiency in hepatocytes blocks the downregulation of lipogenesis by ethyl lactate and exacerbates alcoholic steatosis, inflammation and liver injury. The regulatory mechanism is discussed during the pathophysiological conditions and suggests new lines of research into the therapeutic use of a foodborne small molecule ethyl lactate.

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Ethyl pyruvate: a novel anti‐inflammatory agent

Cited by 154 publications

References 86 publications

Neuroprotective Effects of Ethyl Pyruvate on Brain Energy Metabolism after Ischemia-Reperfusion Injury: A 31P-Nuclear Magnetic Resonance Study

Neuroprotective Effects of Ethyl Pyruvate on Brain Energy Metabolism after Ischemia-Reperfusion Injury: A 31P-Nuclear Magnetic Resonance Study

Combination Treatment with Ethyl Pyruvate and Aspirin Enhances Neuroprotection in the Postischemic Brain

Ethyl Lactate Ameliorates Hepatic Steatosis and Acute‐on‐Chronic Liver Injury in Alcohol‐Associated Liver Disease by Inducing Fibroblast Growth Factor 21

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