Ethyl Pyruvate Ameliorates Liver Injury Secondary to Severe Acute Pancreatitis

Yang, Runkuan; Shaufl, Angel L.; Killeen, Meaghan E.; Fink, Mitchell P.

doi:10.1016/j.jss.2008.04.004

Cited by 40 publications

(38 citation statements)

References 57 publications

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“…Similar results have been observed in preclinical animal models of acute pancreatitis (54). HMGB1 blocking therapy by polyclonal anti-HMGB1 antibodies, A box protein, or ethyl pyruvate administered in five models of acute pancreatitis reduces the incidence of multiple organ failure syndrome and significantly increases survival (56–58). …”

Section: Physiological and Pathophysiological Responses To Hmgb1mentioning

confidence: 99%

HMGB1 Is a Therapeutic Target for Sterile Inflammation and Infection

Andersson

Tracey

2011

Annu. Rev. Immunol.

1,259

1,296

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A key question in immunology concerns how sterile injury activates innate immunity to mediate damaging inflammation in the absence of foreign invaders. The discovery that HMGB1, a ubiquitous nuclear protein, mediates the activation of innate immune responses led directly to the understanding that HMGB1 plays a critical role at the intersection of the host inflammatory response to sterile and infectious threat. HMGB1 is actively released by stimulation of the innate immune system with exogenous pathogen-derived molecules and is passively released by ischemia or cell injury in the absence of invasion. Established molecular mechanisms of HMGB1 binding and signaling through TLR4 reveal signaling pathways that mediate cytokine release and tissue damage. Experimental strategies that selectively target HMGB1 and TLR4 effectively reverse and prevent activation of innate immunity and significantly attenuate damage in diverse models of sterile and infection-induced threat.

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Section: Physiological and Pathophysiological Responses To Hmgb1mentioning

confidence: 99%

HMGB1 Is a Therapeutic Target for Sterile Inflammation and Infection

Andersson

Tracey

2011

Annu. Rev. Immunol.

1,259

1,296

View full text Add to dashboard Cite

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“…In patients and animals with AP, serum levels of HMGB1 are significantly elevated and positively correlate with the severity of this disease (Kocsis et al, 2009; Yasuda et al, 2007; Yasuda et al, 2006). Importantly, inhibiting the release or cytokine activity of HMGB1 (e.g., HMGB1 neutralizing antibody, ethyl pyruvate, danaparoid sodium, cisplatin, A box, antithrombin III, and pyrrolidine dithiocarbamate) confers protection against experimental AP (Cheng et al, 2007; Hagiwara et al, 2009g; Jo et al, 2013; Luan et al, 2013a; Luan et al, 2012; Luan et al, 2013b; Sawa et al, 2006; Weng et al, 2012; Yan et al, 2012a; Yang et al, 2009b; Yang et al, 2008; Yuan et al, 2009; Zhang et al, 2010). However, intracellular HMGB1 in the pancreas protects against acute pancreatitis (Kang et al, 2013b).…”

Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

822

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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“…Yang et al [11] reported that ethyl pyruvate use in a model of severe acute pancreatitis reduced hepatic injury, and that ethyl pyruvate is a powerful anti-inflammatory and antioxidant. In parallel to these findings, our results support the idea that ethyl pyruvate has a protective effect against brain injury resulting from ischemiareperfusion.…”

Section: Discussionmentioning

confidence: 99%