The American Journal of Surgery
Volume 191, Issue 4 , Pages 510-514 , April 2006

Inosine reduces microcirculatory disturbance and inflammatory organ damage in experimental acute pancreatitis in rats

  • Lutz Schneider, M.D.

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
  • ,
  • Matthias Pietschmann, M.D.

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
  • ,
  • Werner Hartwig, M.D.

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
  • ,
  • Sara Sevillano Marcos

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
  • ,
  • Thilo Hackert, M.D.

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
  • ,
  • Martha-Maria Gebhard, M.D.

      Affiliations

    • Department of Experimental Surgery, University of Heidelberg, Heidelberg, Germany
  • ,
  • Waldemar Uhl, M.D.

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
  • ,
  • Markus W. Büchler, M.D.

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
  • ,
  • Jens Werner, M.D.

      Affiliations

    • Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
    • Corresponding Author InformationCorresponding author. Tel: +49-6221-5639692; fax: +49-6221-566922

Received 28 April 2005 ,Revised 27 September 2005

References 

  1. Werner J , Z’Graggen K , Fernandez-del Castillo C , et al.   Specific therapy for local and systemic complications of acute pancreatitis with monoclonal antibodies against ICAM-1 . Ann Surg . 1999;229:834–840 discussion 841–2
  2. Klar E , Werner J . [New pathophysiologic knowledge about acute pancreatitis] . Chirurg . 2000;71:253–264
  3. Steer ML , Meldolesi J . The cell biology of experimental pancreatitis . N Engl J Med . 1987;316:144–150
  4. Gross V , Leser HG , Heinisch A , Scholmerich J . Inflammatory mediators and cytokines—new aspects of the pathophysiology and assessment of severity of acute pancreatitis? . Hepatogastroenterology . 1993;40:522–530
  5. Johnson CD . Platelet-activating factor and platelet-activating factor antagonists in acute pancreatitis . Dig Surg . 1999;16:93–101
  6. Klar E , Schratt W , Foitzik T , et al.   Impact of microcirculatory flow pattern changes on the development of acute edematous and necrotizing pancreatitis in rabbit pancreas . Dig Dis Sci . 1994;39:2639–2644
  7. Hasko G , Nemeth ZH , Vizi ES , et al.   An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice . Eur J Pharmacol . 1998;358:261–268
  8. Schrier DJ , Lesch ME , Wright CD , Gilbertsen RB . The antiinflammatory effects of adenosine receptor agonists on the carrageenan-induced pleural inflammatory response in rats . J Immunol . 1990;145:1874–1879
  9. Szabo C , Scott GS , Virag L , et al.   Suppression of macrophage inflammatory protein (MIP)-1alpha production and collagen-induced arthritis by adenosine receptor agonists . Br J Pharmacol . 1998;125:379–387
  10. Barankiewicz J , Cohen A . Purine nucleotide metabolism in resident and activated rat macrophages in vitro . Eur J Immunol . 1985;15:627–631
  11. Fuss IJ , Marth T , Neurath MF , et al.   Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice . Gastroenterology . 1999;117:1078–1088
  12. Garcia Soriano F , Liaudet L , Marton A , et al.   Inosine improves gut permeability and vascular reactivity in endotoxic shock . Crit Care Med . 2001;29:703–708
  13. Hasko G , Kuhel DG , Chen JF , et al.   Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms . FASEB J . 2000;14:2065–2074
  14. Hasko G , Kuhel DG , Nemeth ZH , et al.   Inosine inhibits inflammatory cytokine production by a posttranscriptional mechanism and protects against endotoxin-induced shock . J Immunol . 2000;164:1013–1019
  15. Hasko G , Szabo C . Regulation of cytokine and chemokine production by transmitters and co-transmitters of the autonomic nervous system . Biochem Pharmacol . 1998;56:1079–1087
  16. Hooper DC , Bagasra O , Marini JC , et al.   Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite (implications for the treatment of multiple sclerosis) . Proc Natl Acad Sci U S A . 1997;94:2528–2533
  17. Liaudet L , Mabley JG , Soriano FG , et al.   Inosine reduces systemic inflammation and improves survival in septic shock induced by cecal ligation and puncture . Am J Respir Crit Care Med . 2001;164:1213–1220
  18. Liaudet L , Mabley JG , Pacher P , et al.   Inosine exerts a broad range of antiinflammatory effects in a murine model of acute lung injury . Ann Surg . 2002;235:568–578
  19. Schmidt J , Rattner DW , Lewandrowski K , et al.   A better model of acute pancreatitis for evaluating therapy . Ann Surg . 1992;215:44–56
  20. Granger DN , Benoit JN , Suzuki M , Grisham MB . Leukocyte adherence to venular endothelium during ischemia-reperfusion . Am J Physiol . 1989;257:G683–G688
  21. Massberg S , Enders G , Leiderer R , et al.   Platelet-endothelial cell interactions during ischemia/reperfusion (the role of P-selectin) . Blood . 1998;92:507–515
  22. Keck T , Werner J , Banafsche R , et al.   Oxygen radicals promote ICAM-1 expression and microcirculatory disturbances in experimental acute pancreatitis . Pancreatology . 2003;3:156–163
  23. Werner J , Dragotakes SC , Fernandez-del Castillo C , et al.   Technetium-99m-labeled white blood cells (a new method to define the local and systemic role of leukocytes in acute experimental pancreatitis) . Ann Surg . 1998;227:86–94
  24. Kusterer K , Poschmann T , Friedemann A , et al.   Arterial constriction, ischemia-reperfusion, and leukocyte adherence in acute pancreatitis . Am J Physiol . 1993;265:G165–G171
  25. Ames BN , Cathcart R , Schwiers E , Hochstein P . Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer (a hypothesis) . Proc Natl Acad Sci U S A . 1981;78:6858–6862
  26. Becker BF , Reinholz N , Ozcelik T , et al.   Uric acid as radical scavenger and antioxidant in the heart . Pflugers Arch . 1989;415:127–135
  27. Szabo C , Zingarelli B , Salzman AL . Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite . Circ Res . 1996;78:1051–1063
  28. Mabley JG , Pacher P , Liaudet L , et al.   Inosine reduces inflammation and improves survival in a murine model of colitis . Am J Physiol Gastrointest Liver Physiol . 2003;284:G138–G144
  29. Norman J , Michael F , Riker A , et al.   Rapid elevation of systemic cytokines during acute pancreatitis and their origination within the pancreas . Surg Forum . 1994;45:148–150
  30. Mazzon E , Dugo L , Li JH , et al.   GPI 6150, a PARP inhibitor, reduces the colon injury caused by dinitrobenzene sulfonic acid in the rat . Biochem Pharmacol . 2002;64:327–337
  31. Zingarelli B , Szabo C , Salzman AL . Blockade of poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis . Gastroenterology . 1999;116:335–345
  32. Gomez G , Sitkovsky MV . Differential requirement for A2a and A3 adenosine receptors for the protective effect of inosine in vivo . Blood . 2003;102:4472–4478
  33. Smiseth OA . Inosine infusion in dogs with acute ischaemic left ventricular failure (favourable effects on myocardial performance and metabolism) . Cardiovasc Res . 1983;17:192–199
  34. de Rougemont D , Brunner FP , Torhorst J , et al.   Superficial nephron obstruction and medullary congestion after ischemic injury (effect of protective treatments) . Nephron . 1982;31:310–320
  35. Al-Mufti RA , Williamson RC , Mathie RT . Increased nitric oxide activity in a rat model of acute pancreatitis . Gut . 1998;43:564–570

PII: S0002-9610(05)00766-X

doi: 10.1016/j.amjsurg.2005.09.009

The American Journal of Surgery
Volume 191, Issue 4 , Pages 510-514 , April 2006