Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock

被引:158
作者
Yang, R
Gallo, DJ
Baust, JJ
Uchiyama, T
Watkins, SK
Delude, RL
Fink, MP
机构
[1] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15261 USA
[3] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA
[4] Univ Pittsburgh, Sch Med, Ctr Biol Imaging, Pittsburgh, PA 15261 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2002年 / 283卷 / 01期
关键词
translocation; bacterial; permeability; mucosal; tumor necrosis factor; cyclooxygenase-2; inducible nitric oxide synthase;
D O I
10.1152/ajpgi.00022.2002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Administration of pyruvate, an effective scavenger of reactive oxygen species, has been shown to be salutary in numerous models of redox-mediated tissue or organ injury. Pyruvate, however, is unstable in solution and, hence, is not attractive for development as a therapeutic agent. Herein, ethyl pyruvate, which is thought to be more stable than the parent compound, was formulated in a calcium-containing balanced salt solution [Ringer ethyl pyruvate solution (REPS)] and evaluated in a murine model of hemorrhagic shock and resuscitation (HS/R). Resuscitation with REPS instead of Ringer lactate solution (RLS) significantly improved survival at 24 h and abrogated bacterial translocation to mesenteric lymph nodes and the development of increased ileal mucosal permeability to FITC-labeled dextran (4,000 Da) at 4 h. Mice treated with REPS instead of RLS also had lower circulating levels of alanine aminotransferase at 4 h. Treatment with REPS instead of RLS decreased activation of nuclear factor-kappaB in liver and colonic mucosa after HS/R and also decreased the expression of inducible nitric oxide synthase, tumor necrosis factor, cyclooxygenase-2, and interleukin-6 mRNA in liver, ileal mucosa, and/or colonic mucosa. These data support the view that resuscitation with REPS modulates the inflammatory response and decreases hepatocellular and gut mucosal injury in mice subjected to HS/R.
引用
收藏
页码:G212 / G221
页数:10
相关论文
共 56 条
  • [1] Oxidative stress causes nuclear Factor-κB activation in acute hypovolemic hemorrhagic shock
    Altavilla, D
    Saitta, A
    Guarini, S
    Galeano, M
    Squadrito, G
    Cucinotta, D
    Santamaria, LB
    Mazzeo, AT
    Campo, GM
    Ferlito, M
    Minutoli, L
    Bazzani, C
    Bertolini, A
    Caputi, AP
    Squadrito, F
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 2001, 30 (10) : 1055 - 1066
  • [2] [Anonymous], [No title captured]
  • [3] HEMORRHAGIC-SHOCK INDUCES BACTERIAL TRANSLOCATION FROM THE GUT
    BAKER, JW
    DEITCH, EA
    LI, M
    BERG, RD
    SPECIAN, RD
    [J]. JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 1988, 28 (07) : 896 - 906
  • [4] Lipid peroxidation is involved in the activation of NF-kappa B by tumor necrosis factor but not interleukin-1 in the human endothelial cell line ECV304 - Lack of involvement of H2O2 in NF-kappa B activation by either cytokine in both primary and transformed endothelial cells
    Bowie, AG
    Moynagh, PN
    ONeill, LAJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (41) : 25941 - 25950
  • [5] PYRUVATE-ENHANCED PHOSPHORYLATION POTENTIAL AND INOTROPISM IN NORMOXIC AND POSTISCHEMIC ISOLATED WORKING HEART - NEAR-COMPLETE PREVENTION OF REPERFUSION CONTRACTILE FAILURE
    BUNGER, R
    MALLET, RT
    HARTMAN, DA
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1989, 180 (01): : 221 - 233
  • [6] BUNTON CA, 1949, NATURE, V163, P144
  • [7] Pyruvate prevents ischemia reperfusion mucosal injury of rat small intestine
    Cicalese, L
    Lee, K
    Schraut, W
    Watkins, S
    Borle, A
    Stanko, R
    [J]. AMERICAN JOURNAL OF SURGERY, 1996, 171 (01) : 97 - 100
  • [8] Pyruvate improves myocardial tolerance to reperfusion injury by acting as an antioxidant: A chemiluminescence study
    Crestanello, JA
    Lingle, DM
    Millili, J
    Whitman, GJ
    [J]. SURGERY, 1998, 124 (01) : 92 - 99
  • [9] PYRUVATE ENHANCES RECOVERY OF RAT HEARTS AFTER ISCHEMIA AND REPERFUSION BY PREVENTING FREE-RADICAL GENERATION
    DEBOER, LWV
    BEKX, PA
    HAN, LH
    STEINKE, L
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 265 (05): : H1571 - H1576
  • [10] HEMORRHAGIC SHOCK-INDUCED BACTERIAL TRANSLOCATION - THE ROLE OF NEUTROPHILS AND HYDROXYL RADICALS
    DEITCH, EA
    BRIDGES, W
    BERG, R
    SPECIAN, RD
    GRANGER, DN
    [J]. JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 1990, 30 (08) : 942 - 952