Transient limb ischemia induces remote preconditioning in liver among rats: The protective role of heme oxygenase-1

Background. We have reported the protective role of heme oxygenase-1 (HO-1) in the mechanism of hypoxic preconditioning. We wish to investigate the role of HO-1 in remote preconditioning (RP) against hepatic ischemia/reperfusion (I/R) injury in rats. Methods. The remote preconditioning was produced by four cycles of 10-min ischemia-reperfusion of the hind limb of rats. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 240 min of reperfusion. Zinc-protoporphyrin IX (ZnPP), a specific inhibitor of HO enzymatic activity, was intra-peritoneally injected 1 hr before the ischemia-reperfusion injury in separate groups of RP rats. Serum alanine transaminase (ALT) levels, expression of hepatic HO-1 protein and mRNA, immunohistochemical staining and HO enzymatic activity were measured. Results. HO-1 was induced in the livers of rats 4 hr after the RP stimuli, and the overexpression persisted for 24 hr. Immunohistochemical staining demonstrated induction of HO-1 in the hepatocytes. The peripheral lymphocytes did not express HO-1 after RP. RP diminished the elevation of serum ALT levels 4 hr after I/R injury (283.7 +/- 167.4 UL-1) when compared with controls (1297.7 +/- 729.3 UL-1) and RP+ ZnPP pretreated groups (1429.9 +/- 750.9 UL-1). The heme oxygenase activity in treated rats also correlated these results (286.8 +/- 34.3 pmol mg(-1) protein hr(-1) for the RP group, 156.3 +/- 27.5 pmol mg(-1) protein hr(-1) for the RP+ ZnPP pretreated group, and 170.6 +/- 19.4 pmol mg(-1) protein hr(-1) for the control group, 144.8 +/- 7.8 pmol mg(-1) protein hr(-1) for the control + ZnPP pretreated group). Conclusion. Our results indicated that the induction of HO-1 in remote preconditioning played a protective role against hepatic I/R injury.