Regulation of postischemic liver injury following different durations of ischemia

Ian N. Hines, Jason M. Hoffman, Heleen Scheerens, Brian J. Day, Hirohisa Harada, Kevin P. Pavlick, Sulaiman Bharwani, Robert Wolf, Bifeng Gao, Sonia Flores, Joe M. McCord, Matthew B. Grisham

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


The objective of this study was to define the relationship among Kupffer cells, O2- production, and TNF-α expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-α, and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-α expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-α but were dependent on Kupffer cells and NADPH oxidase-independent production of O2-. However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived O2-, and TNF-α expression. We conclude that the sources for O2- formation and the relative importance of TNF-α in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia.

Original languageEnglish
Pages (from-to)G536-G545
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number3 47-3
Publication statusPublished - Mar 1 2003
Externally publishedYes


  • Leukocytes
  • NADPH oxidase
  • Proinflammatory cytokines
  • Reactive oxygen species
  • Transplantation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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