Splenectomy ameliorates hepatic ischemia and reperfusion injury mediated by heme oxygenase-1 induction in the rat

Liver. 2002 Dec;22(6):467-73. doi: 10.1034/j.1600-0676.2002.01685.x.

Abstract

Background/aims: Ischemia/reperfusion (I/R) induces severe organic injury. I/R injury seems to be mainly caused by oxidative stress. The aim of this study was to determine the role of the spleen in experimental hepatic I/R injury in the rat. Stress protein heme oxygenase (HO)-1 plays a protective role against the oxidative injury. In normal state, HO-1 is highly expressed in the spleen.

Methods: Liver HO-1 expression was assessed by Western blot before and after splenects. Liver injury was assessed by measurement of ALT and AST and by histopathology.

Results: Although HO-1 was not detected in normal liver, levels of HO-1 protein gradually increased and peaked on 3 days after splenectomy. When splenectomy was performed 3 days prior to the hepatic (45-min) ischemia followed by (2-h) reperfusion, the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT), as markers for hepatic injury, were improved compared to the rats with I/R alone. In addition, prior administration of zinc-protoporphyrin IX, a specific inhibitor of HO, suppressed the protective effect of the splenectomy on the subsequent hepatic I/R injury. Histopathological examination also confirmed these results.

Conclusions: Our findings suggest that the elevated HO-1 levels by splenectomy play a protective role against hepatic I/R injury.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Blotting, Western
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Heme Oxygenase (Decyclizing) / antagonists & inhibitors
  • Heme Oxygenase (Decyclizing) / biosynthesis*
  • Heme Oxygenase-1
  • Liver / enzymology*
  • Liver / pathology
  • Liver Diseases / enzymology*
  • Liver Diseases / pathology
  • Male
  • Protoporphyrins / pharmacology
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / blood
  • Reperfusion Injury / enzymology*
  • Reperfusion Injury / pathology
  • Splenectomy*

Substances

  • Enzyme Inhibitors
  • Protoporphyrins
  • zinc protoporphyrin
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Aspartate Aminotransferases
  • Alanine Transaminase