ArticleAntioxidants & redox signaling2012
Ethyl pyruvate induces heme oxygenase-1 through p38 mitogen-activated protein kinase activation by depletion of glutathione in RAW 264.7 cells and improves survival in septic animals.
Article in Antioxidants & redox signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Multitargeted Neuroprotective Strategies of Ethyl Pyruvate: From Molecular Mechanisms to Clinical Perspectives in CNS Disorders.Biomolecules & therapeutics · 2026Review
- Exogenous Pyruvate in Defense Against Human-Exposure Toxicants: A Review of In Vitro and In Vivo Evidence.International journal of molecular sciences · 2025Review
- Identification of altered blood metabolic pathways in equines following ethyl pyruvate administration using non-targeted metabolomics.Scientific reports · 2024Article
- NRF2 Plays a Crucial Role in the Tolerogenic Effect of Ethyl Pyruvate on Dendritic Cells.International journal of molecular sciences · 2024Article
- Ethyl pyruvate, a versatile protector in inflammation and autoimmunity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Recent Approaches to Targeting Canonical NFJournal of the American Society of Nephrology : JASN · 2021Review
- Pretreatment with chitosan oligosaccharides attenuate experimental severe acute pancreatitis via inhibiting oxidative stress and modulating intestinal homeostasis.Acta pharmacologica Sinica · 2021Article
- Melatonin Ameliorates Inflammation and Oxidative Stress by Suppressing the p38MAPK Signaling Pathway in LPS-Induced Sheep Orchitis.Antioxidants (Basel, Switzerland) · 2020Article
- Ethyl pyruvate inhibits LPS induced IPEC-J2 inflammation and apoptosis through p38 and ERK1/2 pathways.Cell cycle (Georgetown, Tex.) · 2019Article
- Ethyl pyruvate attenuates ventilation-induced diaphragm dysfunction through high-mobility group box-1 in a murine endotoxaemia model.Journal of cellular and molecular medicine · 2019Article
- Ethyl Pyruvate Directly Attenuates Active Secretion of HMGB1 in Proximal Tubular Cells via Induction of Heme Oxygenase-1.Journal of clinical medicine · 2019Article
- Efficacy and Mechanism of Panax Ginseng in Experimental Stroke.Frontiers in neuroscience · 2019Review
- Article
- Phosphorylation of Icariin Can Alleviate the Oxidative Stress Caused by the Duck Hepatitis Virus A through Mitogen-Activated Protein Kinases Signaling Pathways.Frontiers in microbiology · 2017Article
- Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries.Journal of inflammation (London, England) · 2016Review
- Naringin Decreases TNF-α and HMGB1 Release from LPS-Stimulated Macrophages and Improves Survival in a CLP-Induced Sepsis Mice.PloS one · 2016Article
- Glutamine starvation enhances PCV2 replication via the phosphorylation of p38 MAPK, as promoted by reducing glutathione levels.Veterinary research · 2015Article
- Ochratoxin A promotes porcine circovirus type 2 replication in vitro and in vivo.Free radical biology & medicine · 2015Article
- Wuzhi tablet (Schisandra Sphenanthera extract) protects against acetaminophen-induced hepatotoxicity by inhibition of CYP-mediated bioactivation and regulation of NRF2-ARE and p53/p21 pathways.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- HMGB1 in health and disease.Molecular aspects of medicine · 2014Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsWe investigated the molecular mechanism by which ethyl pyruvate (EP) induces heme oxygenase-1 (HO-1) in RAW 264.7 cells and its effect on survival rate in cecal ligation and puncture (CLP)-induced wild-type (WT) and HO-1 knockout (HO-1(-/-)) septic mice.
resultsEP induced HO-1 in a dose- and time-dependent manner, which was mediated through p38 mitogen-activated protein kinase (MAPK) and NF-E2-related factor 2 (Nrf2) signaling cascade in RAW 264.7 cells. EP significantly inhibited the lipopolysaccharide (LPS)-stimulated inducible nitric oxide synthase (iNOS) expression and high-mobility group box 1 (HMGB1) release in RAW 264.7 cells. The inhibitory effect of EP on LPS-stimulated iNOS expression and HMGB1 release was reversed by transfection with siHO-1RNA in RAW 264.7 cells, but EP failed to reduce them in HO-1(-/-) peritoneal macrophages treated with LPS. Moreover, treatment of cells with glutathione ethyl ester (GSH-Et), SB203580 (p38 MAPK inhibitor), siHO-1, or p38-siRNA transfection inhibited anti-inflammatory effect of EP. Interestingly, both HO-1 induction and phosphorylation of p38 by EP were reversed by GSH-Et, and antioxidant redox element-luciferase activity by EP was reversed by SB203580 in LPS-activated cells. EP increased survival and decreased serum HMGB1 in CLP-WT mice, whereas it did not increase survival or decrease circulating HMGB1 in HO-1(-/-) CLP-mice. INNOVATION AND
conclusionOur work provides new insights into the understanding the molecular mechanism by showing that EP induces HO-1 through a p38 MAPK- and NRF2-dependent pathway by decreasing GSH cellular levels. We conclude that EP inhibits proinflammatory response to LPS in macrophages and increases survival in CLP-induced septic mice by upregulation of HO-1 level, in which p38 MAPK and Nrf2 play an important role.
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