Pentoxifylline Interferes with Potental Sources of Free Radical Generation during Endotoxemia

  • Megan R. Lerner
  • Andre K. Balla
  • Michael F. Wilson
  • Daniel J. Brackett
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 366)

Abstract

Increased concentrations of tumor necrosis factor concentrations, activated neutrophils, and inadequate oxygen delivery to tissue are associated with free radical generation and also with endotoxic shock. Pentoxifylline suppresses the synthesis of tumor necrosis factor in endotoxin stimulated macrophages1 and when administered in vivo significantly attenuates circulating tumor necrosis factor and survival in mice challenged with endotoxin.2 Pentoxifylline also inhibits neutrophil activation induced by tumor necrosis factor.3 Additionally, pentoxifylline possesses antithrombotic activity and induces synthesis of endothelial cell prostacyclin, both of which should promote tissue perfusion during endotoxin-induced low flow conditions. This study was designed to determine the effect of pentoxifylline on the development of cardiovascular, metabolic, and pathologic responses to endotoxin.

Keywords

Tumor Necrosis Factor Free Radical Generation Endotoxic Shock Center 3Veterans Affair Medical Antithrombotic Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

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    R.M. Stieter, D.G. Remick, P.A. Ward, R.N. Spengler, J.P. Lynch, J. Larrick, and S.L. Kuhkel, Cellular and molecular regulation of TNF-alpha production by pentoxifylline, Biochem. Biophys. Res. Comm. 155: 1230 (1988).CrossRefGoogle Scholar
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    U.F. Schade, Pentoxifylline increases survival in murine endotoxin shock and decreases formation of tumor necrosis factor, Circ. Shock 31: 171 (1990).PubMedGoogle Scholar
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    H. Zheng, J.J. Crowley, J.C. Chan, H. Hoffmann, J.R. Hatherill, A. Ishizaka, and T.A. Raffin, Attenuation of TNF-induced endothelial cell cytotoxicity and neutrophil chemiluminescence, Am. Rev.Respir. Dis. 42:1073 (1990).Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Megan R. Lerner
    • 1
    • 3
  • Andre K. Balla
    • 2
  • Michael F. Wilson
    • 4
  • Daniel J. Brackett
    • 1
    • 3
  1. 1.Departments of Surgery and AnesthesiologyUniversity of Oklahoma Health Sciences CenterUSA
  2. 2.Department of PathologyUniversity of Oklahoma Health Sciences CenterUSA
  3. 3.Veterans Affairs Medical CenterOklahoma CityUSA
  4. 4.Department of MedicineState University of New York Millard Fillmore HospitalsBuffaloUSA

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