Role of nitric oxide in liver ischemia and reperfusion injury

  • Ian N. Hines
  • Shigeyuki Kawachi
  • Shigeyuki Harada
  • Kevin P. Pavlick
  • Jason M. Hoffman
  • Sulaiman Bharwani
  • Robert E. Wolf
  • Matthew B. Grisham
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


The present study was designed to assess the role of endothelial cell and inducible nitric oxide synthase (eNOS, iNOS)-derived NO in ischemia/reperfusion (I/R)-induced pro-inflammatory cytokine expression and tissue injury in a murine model of hepatic I/R. Forty-five min of partial hepatic ischemia and 3 h of reperfusion resulted in a significant increase in liver injury as assessed by serum alanine aminotransferase and histopathology which occurred in the absence of neutrophil infiltration. Both iNOS and eNOS deficient mice exhibited enhanced liver injury when compared to their wild type (wt) controls again in the absence of neutrophil infiltration. Interestingly, message expression for both tumor necrosis factor-alpha (TNF-a) and interleukin 12 (IL-12) were enhanced in eNOS, but not iNOS-deficient mice at 1 h post-ischemia when compared to their wt controls. In addition, eNOS message expression appeared to be up-regulated between 1 and 3 h of reperfusion in wt mice while iNOS deficient mice exhibited substantial increases at 1 but not 3 h. Taken together, these data demonstrate the ability of eNOS and iNOS to protect the post-ischemic liver, however their mechanisms of action may be very different. (Mol Cell Biochem 234/235: 229–237,2002)

Key words

cytokines inflammation interleukin 12 microcirculation mouse neutrophils reactive oxygen species transplant-tation 


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ian N. Hines
    • 1
  • Shigeyuki Kawachi
    • 1
  • Shigeyuki Harada
    • 1
  • Kevin P. Pavlick
    • 1
  • Jason M. Hoffman
    • 1
  • Sulaiman Bharwani
    • 2
  • Robert E. Wolf
    • 3
  • Matthew B. Grisham
    • 1
  1. 1.Departments of Molecular and Cellular PhysiologyShreveport, LA
  2. 2.Departments of Pediatrics; Medicine
  3. 3.Departments of LSU Health Sciences Center

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