Induction of Heme Oxygenase-1 Improves Cold Preservation Effect of Liver Graft

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Liu Ming^1,2, Wang Bo¹, Zhao Xiaoyu¹, Wang Guangyi¹, and Zhou Hong^1*

¹Institute of Transfusion Medicine, Academy of Military Medical Sciences, Beijing 100850, China; E-mail: zhouhtt@yahoo.com.cn

²Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150086, China

^* To whom correspondence should be addressed.

Received October 12, 2006; Revision received October 31, 2006

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We have examined the protective effect and mechanisms of heme oxygenase-1 (HO-1) induction in rat liver model of ex vivo cold ischemia preservation using cobalt protoporphyrin (CoPP) as HO-1 inducer and zinc protoporphyrin (ZnPP) as HO-1 inhibitor. There was a decrease in both aspartate transaminase and lactate dehydrogenase activities and in malondialdehyde level in liver of the CoPP-treated group compared with controls (p < 0.05). In the CoPP-treated rats, the histological signs of reperfusion injury were much lower than in control. Up-regulation of HO-1 expression was also associated with reduced levels of tumor necrosis factor alpha and interleukin-6. Markedly fewer apoptotic liver cells (determined by TUNEL assay) could be detected in CoPP-treated group compared with the control group. These protective effects were prevented by administration of ZnPP. In conclusion, induction of HO-1 provides protection against liver injury during cold ischemia preservation and improves the preservation of liver graft. The mechanisms underlying these beneficial effects include reduction of oxidative injury and of inflammatory response and prevention of apoptosis.

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KEY WORDS: heme oxygenase-1, cobalt protoporphyrin, organ transplantation, cold ischemia preservation

DOI: 10.1134/S0006297907050112

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