Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma and hemorrhagic shock by reducing local inflammation, NF-kappaB activation and HMGB1 release

PLoS ONE

Volumn 13, Issue 2, 2018, Pages

  Wagner, Nils ^a   Dieteren, Scott ^a   Franz, Niklas ^a   Köhler, Kernt ^b   Mörs, Katharina ^a   Nicin, Luka ^a   Schmidt, Julia ^a   Perl, Mario ^c   Marzi, Ingo ^a   Relja, Borna ^a  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^b JUSTUS LIEBIG UNIVERSITY   (Germany)

^c BG UNFALLKLINIK MURNAU   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTIINFLAMMATORY AGENT; ETHYL PYRUVATE; HEMOGLOBIN; HIGH MOBILITY GROUP B1 PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; SYNAPTOTAGMIN I; UNCLASSIFIED DRUG; HBP1 PROTEIN, RAT; PYRUVIC ACID DERIVATIVE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD ANALYSIS; BLOOD SAMPLING; CELL INFILTRATION; CONTROLLED STUDY; DISEASE ASSOCIATION; ENZYME ACTIVATION; FATTY LIVER; FEMALE; GENE EXPRESSION; HEMOGLOBIN BLOOD LEVEL; HEMORRHAGIC SHOCK; INFLAMMATION; LIVER INJURY; LIVER TISSUE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN SECRETION; RAT; REPERFUSION; RESUSCITATION; SURGICAL TECHNIQUE; SURVIVAL FACTOR; SURVIVAL RATE; THORAX BLUNT TRAUMA; ANIMAL; BLUNT TRAUMA; COMPLICATION; DRUG EFFECTS; INJURIES; LEWIS RAT; LIVER; METABOLISM; THORAX INJURY;

ANIMALS; FEMALE; HMGB1 PROTEIN; INFLAMMATION; LIVER; NF-KAPPA B; PYRUVATES; RATS; RATS, INBRED LEW; SHOCK, HEMORRHAGIC; THORACIC INJURIES; WOUNDS, NONPENETRATING;

EID: 85041950289     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0192171     Document Type: Article

References (61)

1. Sakran JV, Greer SE, Werlin E, McCunn M (2012) Care of the injured worldwide: trauma still the neglected disease of modern society. Scandinavian journal of trauma, resuscitation and emergency medicine 20: 64. https://doi.org/10.1186/1757-7241-20-64 PMID: 22980446
2. Robert Koch-Institut (RKI) GBE Kompakt.
3. Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J et al. (2013) Management of bleeding and coa-gulopathy following major trauma: an updated European guideline. Critical care (London, England) 17 (2): R76.
4. Esmer E, Derst P, Lefering R, Schulz M, Siekmann H et al. (2016) Prehospital assessment of injury type and severity in severely injured patients by emergency physicians. An analysis of the TraumaRegister DGU(R). Der Unfallchirurg.
5. Wutzler S, Lustenberger T, Relja B, Lehnert M, Marzi I (2013) Pathophysiologie des Polytraumas. Inten-sivmedizin und "Timing" der Versorgung. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medi-zen 84 (9): 753–758. https://doi.org/10.1007/s00104-013-2477-0 PMID: 23942889
6. Polito F, Cicciu’ M, Aguennouz M, Cucinotta M, Cristani M et al. (2016) Prognostic value of HMGB1 and oxidative stress markers in multiple trauma patients: A single-centre prospective study. International journal of immunopathology and pharmacology 29 (3): 504–509. https://doi.org/10.1177/0394632016656187 PMID: 27343243
7. Huber-Lang M, Gebhard F, Schmidt CQ, Palmer A, Denk S et al. (2016) Complement therapeutic strategies in trauma, hemorrhagic shock and systemic inflammation—closing Pandora’s box. Seminars in immunology 28 (3): 278–284. https://doi.org/10.1016/j.smim.2016.04.005 PMID: 27157701
8. Kao RL, Xu X, Xenocostas A, Parry N, Mele T et al. (2014) Induction of acute lung inflammation in mice with hemorrhagic shock and resuscitation: role of HMGB1. Journal of inflammation (London, England) 11 (1): 30.
9. Relja B, Hohn C, Bormann F, Seyboth K, Henrich D et al. (2012) Acute alcohol intoxication reduces mortality, inflammatory responses and hepatic injury after haemorrhage and resuscitation in vivo. British journal of pharmacology 165 (4b): 1188–1199. https://doi.org/10.1111/j.1476-5381.2011.01595.x PMID: 21790532
10. Maier M, Geiger EV, Wutzler S, Lehnert M, Wiercinski A et al. (2009) Role of lung contusions on post-traumatic inflammatory response and organ dysfunction in traumatized patients. European journal of trauma and emergency surgery: official publication of the European Trauma Society 35 (5): 463–469.
11. Horst K, Eschbach D, Pfeifer R, Relja B, Sassen M et al. (2016) Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation—Results from a Porcine Long-Term Trauma Model. PloS one 11 (5): e0154788. https://doi.org/10.1371/journal.pone.0154788 PMID: 27144532
12. Abt R, Lustenberger T, Stover JF, Benninger E, Lenzlinger PM et al. (2009) Base excess determined within one hour of admission predicts mortality in patients with severe pelvic fractures and severe hemorrhagic shock. European journal of trauma and emergency surgery: official publication of the European Trauma Society 35 (5): 429.
13. Pierce A, Pittet JF (2014) Inflammatory response to trauma: implications for coagulation and resuscitation. Current opinion in anaesthesiology 27 (2): 246–252. https://doi.org/10.1097/ACO.0000000000000047 PMID: 24419158
14. Partrick DA, Moore FA, Moore EE, Barnett CC JR, Silliman CC (1996) Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. New horizons (Baltimore, Md.) 4 (2): 194–210.
15. Hietbrink F, Koenderman L, Rijkers G, Leenen L (2006) Trauma: the role of the innate immune system. World journal of emergency surgery: WJES 1: 15. https://doi.org/10.1186/1749-7922-1-15 PMID: 16759367
16. Relja B, Schwestka B, Lee VS, Henrich D, Czerny C et al. (2009) Inhibition of c-Jun N-terminal kinase after hemorrhage but before resuscitation mitigates hepatic damage and inflammatory response in male rats. Shock (Augusta, Ga.) 32 (5): 509–516.
17. Tak PP, Firestein GS (2001) NF-kappaB: a key role in inflammatory diseases. The Journal of clinical investigation 107 (1): 7–11. https://doi.org/10.1172/JCI11830 PMID: 11134171
18. Dong W, Cai B, Pena G, Pisarenko V, Vida G et al. (2010) Ethyl pyruvate prevents inflammatory responses and organ damage during resuscitation in porcine hemorrhage. Shock (Augusta, Ga.) 34 (2): 205–213.
19. Levy RM, Mollen KP, Prince JM, Kaczorowski DJ, Vallabhaneni R et al. (2007) Systemic inflammation and remote organ injury following trauma require HMGB1. American journal of physiology. Regulatory, integrative and comparative physiology 293 (4): R1538–44. https://doi.org/10.1152/ajpregu.00272.2007 PMID: 17652366
20. Cotton BA, Guy JS, Morris JA JR, Abumrad NN (2006) The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies. Shock (Augusta, Ga.) 26 (2): 115–121.
21. Karmaniolou II, Theodoraki KA, Orfanos NF, Kostopanagiotou GG, Smyrniotis VE et al. Resuscitation after hemorrhagic shock: the effect on the liver—a review of experimental data. J Anesth 27 (3): 447–460. Available: http://link.springer.com.proxy.ub.uni-frankfurt.de/content/pdf/10.1007%2Fs00540-0121543-y.pdf. https://doi.org/10.1007/s00540-012-1543-y PMID: 23275009
22. Fink MP (2008) Ethyl pyruvate. Current opinion in anaesthesiology 21 (2): 160–167. https://doi.org/10.1097/ACO.0b013e3282f63c2e PMID: 18443482
23. Relja B, Omid N, Wagner N, Mors K, Werner I et al. (2016) Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-kappaB in vitro but have a low impact on hepatocellular cells. International journal of molecular medicine 37 (2): 517–525. https://doi.org/10.3892/ijmm.2015.2431 PMID: 26677054
24. Pulathan Z, Altun G, Hemsinli D, Mentese A, Yulug E et al. (2014) Role of ethyl pyruvate in systemic inflammatory response and lung injury in an experimental model of ruptured abdominal aortic aneurysm. BioMed research international 2014: 857109. https://doi.org/10.1155/2014/857109 PMID: 24575415
25. Fang R, Zheng X, Zhang M (2016) Ethyl pyruvate alleviates early brain injury following subarachnoid hemorrhage in rats. Acta neurochirurgica 158 (6): 1069–1076. https://doi.org/10.1007/s00701-016-2795-3 PMID: 27072679
26. Shen M, Lu J, Dai W, Wang F, Xu L et al. (2013) Ethyl pyruvate ameliorates hepatic ischemia-reperfusion injury by inhibiting intrinsic pathway of apoptosis and autophagy. Mediators of inflammation 2013: 461536. https://doi.org/10.1155/2013/461536 PMID: 24453420
27. Yang R, Zhu S, Tonnessen TI (2016) Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries. Journal of inflammation (London, England) 13: 37.
28. Worlein JM, Baker K, Bloomsmith M, Coleman K, Koban TL (2011) The Eighth Edition of the Guide for the Care and Use of Laboratory Animals (2011). Implications for Behavioral Management. american journal of primatology 73: 98.
29. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS biology 8 (6): e1000412. https://doi.org/10.1371/journal.pbio.1000412 PMID: 20613859
30. Seitz DH, Perl M, Mangold S, Neddermann A, Braumuller ST et al. (2008) Pulmonary contusion induces alveolar type 2 epithelial cell apoptosis: role of alveolar macrophages and neutrophils. Shock (Augusta, Ga.) 30 (5): 537–544.
31. Liener UC, Knoferl MW, Strater J, Barth TF, Pauser EM et al. (2003) Induction of apoptosis following blunt chest trauma. Shock (Augusta, Ga.) 20 (6): 511–516.
32. Lehnert M, Relja B, Sun-Young LV, Schwestka B, Henrich D et al. (2008) A peptide inhibitor of C-jun N-terminal kinase modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation. Shock (Augusta, Ga.) 30 (2): 159–165.
33. Relja B, Tottel E, Breig L, Henrich D, Schneider H et al. (2012) Plant polyphenols attenuate hepatic injury after hemorrhage/resuscitation by inhibition of apoptosis, oxidative stress, and inflammation via NF-kappaB in rats. European journal of nutrition 51 (3): 311–321. https://doi.org/10.1007/s00394-011-0216-1 PMID: 21698494
34. Relja B, Wilhelm K, Wang M, Henrich D, Marzi I et al. (2012) Acute ethanol gavage attenuates hemorrhage/resuscitation-induced hepatic oxidative stress in rats. Oxidative medicine and cellular longevity 2012: 983427. https://doi.org/10.1155/2012/983427 PMID: 22550557
35. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nature protocols 3 (6): 1101–1108. PMID: 18546601
36. Kao KK, Fink MP (2010) The biochemical basis for the anti-inflammatory and cytoprotective actions of ethyl pyruvate and related compounds. Biochemical pharmacology 80 (2): 151–159. https://doi.org/10.1016/j.bcp.2010.03.007 PMID: 20230800
37. Salahudeen AK, Clark EC, Nath KA (1991) Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo. The Journal of clinical investigation 88 (6): 1886–1893. https://doi.org/10.1172/JCI115511 PMID: 1752950
38. Mongan PD, Fontana JL, Chen R, Bünger R (1999) Intravenous pyruvate prolongs survival during hemorrhagic shock in swine. The American journal of physiology 277 (6 Pt 2): H2253–63.
39. Slovin PN, Huang CJ, Cade JR, Wood CE, Nasiroglu O et al. (2001) Sodium pyruvate is better than sodium chloride as a resuscitation solution in a rodent model of profound hemorrhagic shock. Resuscitation 50 (1): 109–115. PMID: 11719137
40. Sileri P, Schena S, Morini S, Rastellini C, Pham S et al. (2001) Pyruvate inhibits hepatic ischemia-reperfusion injury in rats. Transplantation 72 (1): 27–30. PMID: 11468530
41. Zeng J, Liu J, Yang G-Y, Kelly MJS, James TL et al. (2007) Exogenous ethyl pyruvate versus pyruvate during metabolic recovery after oxidative stress in neonatal rat cerebrocortical slices. Anesthesiology 107 (4): 630–640. https://doi.org/10.1097/01.anes.0000281898.01966.1e PMID: 17893460
42. Sharma P, Mongan PD (2010) Hypertonic sodium pyruvate solution is more effective than Ringer’s ethyl pyruvate in the treatment of hemorrhagic shock. Shock (Augusta, Ga.) 33 (5): 532–540.
43. Bennett-Guerrero E, Swaminathan M, Grigore AM, Roach GW, Aberle LG et al. (2009) A phase II multi-center double-blind placebo-controlled study of ethyl pyruvate in high-risk patients undergoing cardiac surgery with cardiopulmonary bypass. Journal of cardiothoracic and vascular anesthesia 23 (3): 324–329. https://doi.org/10.1053/j.jvca.2008.08.005 PMID: 18835526
44. Rixen D, Siegel JH (2005) Bench-to-bedside review: oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock. Critical care (London, England) 9 (5): 441–453.
45. Davis JW, Parks SN, Kaups KL, Gladen HE, O’Donnell-Nicol S (1996) Admission base deficit predicts transfusion requirements and risk of complications. The Journal of trauma 41 (5): 769–774. PMID: 8913202
46. Hauser B, Kick J, Asfar P, Ehrmann U, Albicini M et al. (2005) Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia. Critical care medicine 33 (9): 2034–2042. PMID: 16148477
47. Sims CA, Wattanasirichaigoon S, Menconi MJ, Ajami AM, Fink MP (2001) Ringer’s ethyl pyruvate solution ameliorates ischemia/reperfusion-induced intestinal mucosal injury in rats. Critical care medicine 29 (8): 1513–1518. PMID: 11505117
48. Mulier KE, Beilman GJ, Conroy MJ, Taylor JH, Skarda DE et al. (2005) Ringer’s ethyl pyruvate in hemorrhagic shock and resuscitation does not improve early hemodynamics or tissue energetics. Shock (Augusta, Ga.) 23 (3): 248–252.
49. Mutschler M, Nienaber U, Brockamp T, Wafaisade A, Fabian T et al. (2013) Renaissance of base deficit for the initial assessment of trauma patients: a base deficit-based classification for hypovolemic shock developed on data from 16,305 patients derived from the TraumaRegister DGU(R). Critical care (London, England) 17 (2): R42.
50. Rixen D, Raum M, Bouillon B, Lefering R, Neugebauer E (2001) Base deficit development and its prognostic significance in posttrauma critical illness: an analysis by the trauma registry of the Deutsche Gesellschaft fur unfallchirurgie. Shock (Augusta, Ga.) 15 (2): 83–89.
51. Davis JW, Shackford SR, Mackersie RC, Hoyt DB (1988) Base deficit as a guide to volume resuscitation. The Journal of trauma 28 (10): 1464–1467. PMID: 3172306
52. Yang R, Shaufl AL, Killeen ME, Fink MP (2009) Ethyl pyruvate ameliorates liver injury secondary to severe acute pancreatitis. The Journal of surgical research 153 (2): 302–309. https://doi.org/10.1016/j.jss.2008.04.004 PMID: 19027919
53. Tsung A, Kaizu T, Nakao A, Shao L, Bucher B et al. (2005) Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptosis. Transplantation 79 (2): 196–204. PMID: 15665768
54. Yang R, Han X, Delude RL, Fink MP (2003) Ethyl pyruvate ameliorates acute alcohol-induced liver injury and inflammation in mice. The Journal of laboratory and clinical medicine 142 (5): 322–331. https://doi.org/10.1016/S0022-2143(03)00138-0 PMID: 14647036
55. Luan ZG, Zhang H, Ma XC, Zhang C, Guo RX (2012) Therapeutic treatment with ethyl pyruvate attenuates the severity of liver injury in rats with severe acute pancreatitis. Pancreas 41 (5): 729–737. https://doi.org/10.1097/MPA.0b013e31823cd3ef PMID: 22699144
56. Liang Y, Zhou Y, Shen P (2004) NF-kappaB and its regulation on the immune system. Cellular & molecular immunology 1 (5): 343–350.
57. Ulloa L, Ochani M, Yang H, Tanovic M, Halperin D et al. (2002) Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proceedings of the National Academy of Sciences of the United States of America 99 (19): 12351–12356. https://doi.org/10.1073/pnas.192222999PMID: 12209006
58. Han Y, Englert JA, Yang R, Delude RL, Fink MP (2005) Ethyl pyruvate inhibits nuclear factor-kappaB-dependent signaling by directly targeting p65. The Journal of pharmacology and experimental therapeutics 312 (3): 1097–1105. https://doi.org/10.1124/jpet.104.079707 PMID: 15525791
59. Yu Y, Yu Y, Liu M, Yu P, Liu G et al. (2016) Ethyl pyruvate attenuated coxsackievirus B3-induced acute viral myocarditis by suppression of HMGB1/RAGE/NF-KappaB pathway. SpringerPlus 5: 215. https://doi.org/10.1186/s40064-016-1857-6 PMID: 27026909
60. Zhang M, Hu X, Li S, Lu C, Li J et al. (2017) Hepatoprotective effects of ethyl pyruvate against CCl4-induced hepatic fibrosis via inhibition of TLR4/NF-κB signaling and up-regulation of MMPs/TIMPs ratio. Clinics and research in hepatology and gastroenterology.
61. Shen M, Lu J, Cheng P, Lin C, Dai W et al. (2014) Ethyl pyruvate pretreatment attenuates concanavalin a-induced autoimmune hepatitis in mice. PloS one 9 (2): e87977. https://doi.org/10.1371/journal.pone.0087977 PMID: 24498418