Protective role of heme oxygenase-1 against liver damage caused by hepatic ischemia and reperfusion in rats.
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| 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.
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| Authors | Nari Yun, Hyun-Ae Eum, Sun-Mee Lee |
| Journal | Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 13 Issue 10 Pg. 1503-12 (Nov 15 2010) ISSN: 1557-7716 [Electronic] United States |
| PMID | 20446775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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