Induction of the protooncogene c-fos and recovery of cytosolic adenosine triphosphate in reperfused liver after transient warm ischemia: effect of nitrone free-radical spin-trap agents

Surgery. 1991 Aug;110(2):184-91.


Ischemia and reperfusion stimulate several adenosine triphosphate (ATP)-dependent processes involving release of substances including free radicals. This cellular response is mediated through receptors responsive to transcriptional products of gene expression; c-fos acts as a transcriptional factor involved in the regulation of genes associated with cellular proliferation and differentiation. We hypothesized that nitrone free-radical spin traps promote restoration of cytosolic ATP during reperfusion and prevent c-fos induction. Four control rats had no ischemia. Global hepatic ischemia was induced in 19 rats in four groups: saline solution, phenyl-N-tert-butyl nitrone (PBN), alpha 1-pyridyl-N-oxide N-tert-butyl nitrone (POBN), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). ATP and intracellular pH were measured at intervals before, during, and after ischemia. At 90 minutes of reperfusion, liver c-fos mRNA was measured. A fourfold elevation of c-fos occurred in the saline-treated group (p less than 0.001). PBN and POBN groups did not differ from the saline group. DMPO resulted in significantly less induction of c-fos than did NS. ATP depletion and recovery in all treatment groups was similar to that of the saline group. We conclude that (1) nitrone spin traps do not prevent c-fos induction or alter the pattern of ATP recovery after hepatic ischemia and reperfusion and (2) c-fos induction is not necessary for restoration of ATP, but the rate of ATP restoration is inversely related to c-fos induction.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Blotting, Northern
  • Cytosol / metabolism
  • Free Radicals*
  • Gene Expression Regulation / drug effects
  • Hydrogen-Ion Concentration
  • Ischemia / metabolism
  • Liver / blood supply*
  • Magnetic Resonance Spectroscopy
  • Male
  • Nitrogen Oxides / pharmacology*
  • Proto-Oncogenes / physiology*
  • RNA / isolation & purification
  • Rats
  • Rats, Inbred Strains
  • Reperfusion Injury / metabolism*
  • Time Factors


  • Free Radicals
  • Nitrogen Oxides
  • nitrones
  • RNA
  • Adenosine Triphosphate