Splenectomy ameliorates hepatic ischemia and reperfusion injury mediated by heme oxygenase-1 induction in the rat.
OBJECTIVE
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.
Ito
Koji
K
Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Ozasa
Hisashi
H
Yoneya
Rika
R
Horikawa
Saburo
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology* / Q000473:pathology; D008297:Male; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D013156:Splenectomy
D004791:Enzyme Inhibitors; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase