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Titolo:
Novel iron chelator in combination with a P-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model
Autore:
Amersi, F; Dulkanchainun, T; Nelson, SK; Farmer, DG; Kato, H; Zaky, J; Melinek, J; Shaw, GD; Kupiec-Weglinski, JW; Horwitz, LD; Horwitz, MA; Busuttil, RW;
Indirizzi:
Univ Calif Los Angeles, Dumont UCLA Transplant Ctr, Div Liver & Pancreas Transplantat, Dept Surg, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Sch Med, Div Infect Dis, Dept Med, Los Angeles, CA90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA90095 USA Univ Colorado, Hlth Sci Ctr, Dept Med, Div Cardiol, Denver, CO 80262 USA Univ Colorado Denver CO USA 80262 Med, Div Cardiol, Denver, CO 80262 USA Webb Waring Antioxidant Res Inst, Denver, CO 80262 USA Webb Waring Antioxidant Res Inst Denver CO USA 80262 Denver, CO 80262 USA
Titolo Testata:
TRANSPLANTATION
fascicolo: 1, volume: 71, anno: 2001,
pagine: 112 - 118
SICI:
0041-1337(20010115)71:1<112:NICICW>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOTAL HEPATIC ISCHEMIA; REPERFUSION INJURY; MYCOBACTERIUM-TUBERCULOSIS; ENDOTHELIAL-CELLS; HYDROGEN-PEROXIDE; EXPRESSION; INFILTRATION; EXOCHELINS; PROTEINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Busuttil, RW Univ Calif Los Angeles, Dumont UCLA Transplant Ctr, Div Liver& Pancreas Transplantat, Dept Surg, 77-120 Ctr Hlth Sci,10833 Le Conte Ave, Los Angeles, CA 90095 USA Univ Calif Los Angeles 77-120 Ctr Hlth Sci,10833 Le Conte Ave Los Angeles CA USA 90095
Citazione:
F. Amersi et al., "Novel iron chelator in combination with a P-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model", TRANSPLANT, 71(1), 2001, pp. 112-118

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 oxygenintermediates. 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 degreesC 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 timeof harvest; and a group that received 0.4 mg/kg rPSGL-Ig plus 1 mu mol 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 theend 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 controlsin 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 Banff's 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. rPSCL-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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 02:04:58