Abstract
Ethyl pyruvate (EP) is a simple derivative of pyruvic acid, which is an important endogenous metabolite that can scavenge reactive oxygen species (ROS). Treatment with EP is able to ameliorate systemic inflammation and multiple organ dysfunctions in multiple animal models, such as acute pancreatitis, alcoholic liver injury, acute respiratory distress syndrome (ARDS), acute viral myocarditis, acute kidney injury and sepsis. Recent studies have demonstrated that prolonged treatment with EP can ameliorate experimental ulcerative colitis and slow multiple tumor growth. It has become evident that EP has pharmacological anti-inflammatory effect to inhibit multiple early inflammatory cytokines and the late inflammatory cytokine HMGB1 release, and the anti-tumor activity is likely associated with its anti-inflammatory effect. EP has been tested in human volunteers and in a clinical trial of patients undergoing cardiac surgery in USA and shown to be safe at clinical relevant doses, even though EP fails to improve outcome of the heart surgery, EP is still a promising agent to treat patients with multiple inflammatory organ injuries and the other clinical trials are on the way. This review focuses on how EP is able to ameliorate multiple organ injuries and summarize recently published EP investigations. Graphical The targets of the anti-inflammatory agent EP
Highlights
Pyruvate is the final product of glycolysis and the starting substrate for the tricarboxylic acid (TCA) cycle, and this important metabolic intermediate is an effective scavenger of hydrogen peroxide and other reactive oxygen species (ROS) [1, 2]
The inflammatory cytokines play a crucial role in the pathogenesis of severe acute pancreatitis (SAP) [3, 8, 9]; the damaged pancreatic acinar cells and the activated inflammatory cells produce a large amount of oxygen radicals in Acute pancreatitis (AP), and these ROS molecules can damage the lipid membranes of pancreatic acinar cells, they can injure the capillary endothelium in the circulation to accelerate the progress of SAP [7]
Hepatic I/R induces significantly increased hepatic expression of TNF-α, IL-6, High mobility group box 1 (HMGB1) and NF-kB activation, and hepatic I/R induces markedly increased hepatic expression of Bcl-2, Bax, Beclin-1 and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, all of these changes are significantly reduced by Ethyl pyruvate (EP) treatment (1 h before the ischemia procedure, a single dose of EP was intraperitoneally injected to animals in the 20 mg/kg group, the 40 mg/kg group and the 80 mg/kg group, liver tissue samples were obtained 4 h, 6 h and 16 h after I/R), suggesting that EP ameliorates hepatic I/R injury via its antiinflammatory and its anti-apoptosis effect
Summary
Pyruvate is the final product of glycolysis and the starting substrate for the tricarboxylic acid (TCA) cycle, and this important metabolic intermediate is an effective scavenger of hydrogen peroxide and other ROS [1, 2].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
