title: Ethyl pyruvate ameliorates liver injury secondary to severe acute pancreatitis.
abstract: BACKGROUND
  Ethyl pyruvate (EP) is capable of significantly decreasing serum alanine aminotransferase and reducing hepatic necrosis in a murine model of severe acute pancreatitis (SAP); however, the working mechanism is still unclear. This study aims to elucidate the underlying mechanism of EP solution ameliorating SAP-induced liver injury and provide a new therapeutic agent to treat liver injury.
  
  
  METHODS
  Acute necrotizing pancreatitis was induced in C57Bl/6 male mice by feeding the animals a choline-deficient diet supplemented with 0.5% ethionine for 24 h; then the animals were challenged with 7 hourly 50 mug/kg cerulein i.p. injections and a single i.p. injection of Escherichia coli lipopolysaccharide (4 mg/kg). Two hours after the injection of lipopolysaccharide, 40 mg/kg EP, the same volume of Ringers lactate solution (RLS), or saline solution were i.p. injected to animals of EP, RLS, and control groups every 6 h for a total 48-h period.
  
  
  RESULTS
  When mice were treated with EP, hepatic mRNA expression of tumor necrosis factor-alpha, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 was significantly lower than that in pancreatitis mice treated with RLS. Compared to RLS treatment, treatment with EP significantly decreased the number of inflammatory cell infiltration and markedly inhibited hepatic nuclear factor-kappa B DNA binding; EP therapy dramatically inhibited high motility group B1 release from inflamed hepatic tissue and significantly decreased the concentration of hepatic tissue malondialdehyde, an oxidative stress parameter. EP treatment also significantly improved body circulating blood volume.
  
  
  CONCLUSIONS
  EP is a potent anti-inflammatory and anti-oxidative agent to ameliorate hepatic local inflammatory response and resultantly decreases liver injury secondary to SAP.
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15261, USA. yangr@ccm.upmc.edu
authors.forename: Runkuan
authors.initials: R
authors.lastname: Yang
authors.forename: Angel L
authors.initials: AL
authors.lastname: Shaufl
authors.forename: Meaghan E
authors.initials: ME
authors.lastname: Killeen
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Fink
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications*; D011773:Pyruvates / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D051793:Hypoxia-Inducible Factor 1; D015850:Interleukin-6; D016328:NF-kappa B; D011773:Pyruvates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2