Role of sialyl Lewis(x) in total hepatic ischemia and reperfusion.
BACKGROUND
Neutrophil adhesion and migration is associated with hepatic ischemia and reperfusion. The role of a Sialyl Lewis(x) (SLe)(x) oligosaccharide, a ligand for selections, was studied in hepatic ischemia and reperfusion injury.


METHODS
Total hepatic ischemia was produced in rats for 90 minutes using an extracorporeal portosystemic shunt. To assess the role of SLe(x) in hepatic ischemia and reperfusion injury, 25 mg/kg of an SLe(x) analog, CY-1503, was given five minutes before reperfusion or at reperfusion. Biochemical tests of hepatic injury, myeloperoxidase activity in hepatic tissue, and histologic studies, including neutrophil infiltration determined by the naphthol esterase technique, were analyzed six hours after reperfusion.


RESULTS
Significantly improved protection in biochemical hepatic injury tests (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) was noted between the ischemic and the SLe(x) treated groups. Myeloperoxidase activity and polymorphonuclear cell infiltration in hepatic tissue were decreased in the SLe(x) groups. Histologic protection from hepatic damage was observed in the treated groups.


CONCLUSIONS
The SLe(x) oligosaccharide analog, CY-1503, had an important protective role in hepatic ischemia and reperfusion injury. Modulation of SLe(x) in the neutrophil decreased the adhesion of polymorphonuclear cells and their subsequent migration after hepatic ischemia and reperfusion.
Misawa
K
K
Surgical Research Institute, Borgess Medical Center, Kalamazoo, MI 49001, USA.
Toledo-Pereyra
L H
LH
Phillips
M L
ML
Garcia-Cirado
F J
FJ
Lopez-Neblina
F
F
Paez-Rollys
A
A
D000818:Animals; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007983:Lewis Blood Group Antigens; D008024:Ligands; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
C090410:CY 1503; D007983:Lewis Blood Group Antigens; D008024:Ligands; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen