Abstract | INTRODUCTION: Hepatocellular injury caused by ischemia-reperfusion of the liver occurs in a number of clinical situations including major trauma, elective surgery of the liver, and liver transplantation. Several strategies have been used to prevent liver injury following ischemia-reperfusion (I/R). Among these, ischemic preconditioning has shown promise as a preventative approach. In this manuscript, we hypothesized that use of remote ischemic preconditioning by brief hindlimb ischemia might prevent liver dysfunction in a mouse model of liver I/R. METHODS: RESULTS: Antecedent hindlimb ischemia (10 minutes) lessened I/R-induced elevation of serum alanine aminotransferase compared with untreated I/R animals. This protection correlated with a reduction in serum TNF-alpha protein levels as well as liver TNF-alpha mRNA and apoptosis. High Mobility Group-Box 1 (HMG-B1) levels in the blood were elevated after hindlimb ischemia and injection of HMG-B1 prior to liver recapitulated the protective effect of hindlimb occlusion. TLR4-mutant HeJ mice did not demonstrate protection with hindlimb preconditioning. CONCLUSIONS: Brief hindlimb occlusion prevents liver I/R injury. This effect appears to be related to release of HMG-B1 and is dependent on the presence of a functional TLR4. Remote ischemia preconditioning represents a novel approach to preventing distant organ injury.
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Authors | Feng Wang, Simone E Birch, Ruijan He, Patrick Tawadros, Katalin Szaszi, Andras Kapus, Ori D Rotstein |
Journal | Annals of surgery
(Ann Surg)
Vol. 251
Issue 2
Pg. 292-9
(Feb 2010)
ISSN: 1528-1140 [Electronic] United States |
PMID | 19858701
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hbp1 protein, mouse
- High Mobility Group Proteins
- Repressor Proteins
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Topics |
- Animals
- Female
- High Mobility Group Proteins
(physiology)
- Hindlimb
(blood supply)
- Ischemic Preconditioning
(methods)
- Liver
(blood supply)
- Mice
- Mice, Inbred C57BL
- Reperfusion Injury
(prevention & control)
- Repressor Proteins
(physiology)
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