Journal article
A novel iron chelator in combination with a p-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model
Transplantation, Vol.71(1), pp.112-118
01/15/2001
DOI: 10.1097/00007890-200101150-00018
PMID: 11211175
Abstract
Background: Hepatic ischemia/reperfusion (I/R) injury is associated with early and late graft failure after liver transplantation. A major mechanism is leukocyte adhesion to endothelium followed by release of reactive oxygen intermediates. We examined whether desferriexochelin 772SM (D-Exo), a lipid soluble iron chelator that prevents hydroxyl radical formation, can enhance the capacity of recombinant P-selectin glycoprotein ligand immunoglobulin (rPSGL-Ig), a glycoprotein that binds to P-selectin and inhibits neutrophil adhesion, to protect against I/R injury in an ex vivo rat liver model.
Methods: Rat livers were harvested and stored for 6 hr at 4 degrees C in University of Wisconsin solution and then perfused with oxygenated whole blood for 2 hr. Three groups were studied (n=6 rats/group): an untreated control group; a group that received 0.4 mg/kg rPSGL-Ig intraportally at the time of harvest; and a group that received 0.4 mg/kg rPSGL-Ig plus 1 micromol D-Exo intraportally both at the time of harvest and at the onset of reperfusion. Liver portal venous blood flow was assessed during perfusion, and at the end of each experiment, liver samples were collected for blinded histological evaluation and biochemical analyses.
Results: Livers treated with D-Exo + rPSGL-Ig had significantly higher blood flow than livers treated with rPSGL-1Ig alone (P<0.05), and both treatment groups had higher blood flow than controls (P<0.001). Production of carbonyl proteins, a protein oxidation product, was significantly reduced in the D-Exo + rPSGL-1Ig group (P<0.02 vs. controls), but not in the rPSGL-Ig alone group. Total reduced glutathione was significantly higher than controls in the D-Exo + rPSGL-Ig group (P<0.001 vs. controls), but not in the rPSGL-Ig alone group, indicating less oxidative stress in the D-Exo-treated group. Production of malondialdehyde, an index of lipid peroxidation, was significantly less than controls in both treatment groups (P<0.03). Histopathological findings paralleled these results with Banffs scores of 3.3+/-0.5, 1.8+/-0.4, and 1.3+/-0.5 in the control, rPSGL-Ig alone, and D-Exo plus rPSGL-Ig groups, resp.
Conclusion: rPSGL-Ig provides partial protection against I/R injury to ex vivo rat livers; however, the addition of D-Exo substantially increases protection by reducing oxidative injury. These findings may have clinical relevance in preventing the consequences of I/R injury after liver transplantation.
Details
- Title: Subtitle
- A novel iron chelator in combination with a p-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model
- Creators
- Farin Amersi - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesTom Dulkanchainun - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesMarcus A Horwitz - Division of Infectious Diseases, Department of Medicine, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesRonald W Busuttil - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesSally K Nelson - Webb-Waring Antioxidant Research Institute, Denver, CO 80262, United StatesDouglas G Farmer - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesHirohisa Kato - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesJoseph Zaky - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesJudy Melinek - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesGray D Shaw - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesJerzy W KUPIEC-WEGLINSKI - The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA School of Medicine, Los Angeles, Los Angeles, CA 90095, United StatesLawrence D Horwitz - University of Colorado Health
- Resource Type
- Journal article
- Publication Details
- Transplantation, Vol.71(1), pp.112-118
- DOI
- 10.1097/00007890-200101150-00018
- PMID
- 11211175
- NLM abbreviation
- Transplantation
- ISSN
- 0041-1337
- eISSN
- 1534-6080
- Publisher
- Lippincott
- Language
- English
- Date published
- 01/15/2001
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984656592302771
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