The protective role of heme oxygenase-1 on the liver after hypoxic preconditioning in rats.
BACKGROUND
Hypoxic preconditioning (HP) confers cytoprotection against ischemia/reperfusion (I/R) injury. This effect is in part attributable to the induction of heme oxygenase (HO)-1. This experiment evaluates liver cell damage after I/R injury in HP rats.


METHODS
HP rats were prepared by exposure (15 hr/day) to an altitude chamber (5500 m) for 2 weeks. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 180 min of reperfusion. Zinc (Zn) protoporphyrin (PP), a specific inhibitor of HO enzymatic activity, was subcutaneously injected 1 hr before the I/R injury into separate groups of sea-level (SL) control and HP rats. Serum alanine aminotransferase (ALT) levels, liver HO-1 mRNA and protein, and HO enzymatic activity were measured.


RESULTS
HO-1 was induced in the livers of rats exposed to HP. The levels of HO-1 mRNA and protein were obviously overexpressed after 2 weeks of HP. HP diminished the elevation of serum ALT levels after I/R injury (83.7+/- 4.9 U/L) when compared with SL controls (280.8+/-19.4 U/L) and HP+ZnPP-pretreated groups (151.3+/-4.4 U/L). The HO activity in treated rats also was correlated with these results (237.9+/-19.8 pmol/mg of protein per hour for the HP group, 164.3+/-12.7 pmol/mg of protein per hour for the HP+ZnPP group, and 182.6+/-8 pmol/mg of protein per hour for the SL controls).


CONCLUSIONS
The authors' results indicated that the induction of HO-1 in hypoxic preconditioning played a protective role against hepatic I/R injury.
Lai
I-Rue
IR
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
Ma
Ming-Chieh
MC
Chen
Chau-Fong
CF
Chang
King-Jen
KJ
D000818:Animals; D019610:Cytoprotection; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000502:physiology*; D051547:Heme Oxygenase-1; D000860:Hypoxia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1