Protective role of heme oxygenase-1 against liver damage caused by hepatic ischemia and reperfusion in rats

Antioxid Redox Signal. 2010 Nov 15;13(10):1503-12. doi: 10.1089/ars.2009.2873.

Abstract

This study investigated the time course of heme oxygenase (HO)-1 expression and the role of endogenous HO-1 in hepatic ischemia and reperfusion (I/R). Rats were pretreated with hemin, an HO-1 inducer, and zinc protoporphyrin (ZnPP), an HO-1 inhibitor. Hepatic HO activity increased at 1 h after reperfusion, reaching a maximum at 6 h after reperfusion and then declined. HO-1 mRNA and protein expression in I/R liver were upregulated prior to reperfusion and highly induced again by reperfusion. The ALT level was upregulated at all time points, with a peak at 4-6 h. This increase was augmented by ZnPP but attenuated by hemin. Lipid peroxidation and serum HMGB1 release significantly increased at 1 h after reperfusion and remained elevated throughout the 24 h of reperfusion period, whereas the glutathione content decreased markedly at 4-6 h after reperfusion. These changes were attenuated by hemin but augmented by ZnPP. The levels of serum TNF-α, iNOS, and COX-2 protein and mRNA expressions were upregulated after reperfusion, further enhanced by ZnPP, and suppressed by hemin. HO-1 overexpression protects the liver against I/R injury by modulating oxidative stress and proinflammatory mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • HMGB1 Protein / blood
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Hemin / administration & dosage
  • Lipid Peroxidation
  • Liver Diseases / enzymology*
  • Liver Diseases / metabolism
  • Liver Diseases / prevention & control*
  • Male
  • Protoporphyrins / administration & dosage
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Time Factors

Substances

  • HMGB1 Protein
  • Hbp1 protein, rat
  • Protoporphyrins
  • RNA, Messenger
  • zinc protoporphyrin
  • Hemin
  • Heme Oxygenase-1