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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Chemical References |
- HMGB1 Protein
- Hbp1 protein, rat
- Protoporphyrins
- RNA, Messenger
- zinc protoporphyrin
- Hemin
- Heme Oxygenase-1
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Topics |
- Animals
- HMGB1 Protein
(blood)
- Heme Oxygenase-1
(genetics, metabolism)
- Hemin
(administration & dosage)
- Lipid Peroxidation
- Liver Diseases
(enzymology, metabolism, prevention & control)
- Male
- Protoporphyrins
(administration & dosage)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(metabolism)
- Time Factors
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