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

Authors


Saburo Horikawa, Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101–0062, Japan. Tel: 81 3 5280 8076. Fax: 81 3 5280 8075. e-mail: hori-pbc@mri.tmd.ac.jp

Abstract

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.

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