The sialyl lewis X analogue, CY-1503, down-regulates leucocyte-endothelium interactions and the inflammatory response

• Published in: The European journal of surgery Vol. 165; no. 7; pp. 690 - 697
• Main Authors: Garcia-Criado, Francisco J., Valdunciel-Garcia, Joaquin J., Garcia-Garcia, Jacinto, Ramos-Boyero, Manuel, Sanchez-Fernandez, Jose, Zambrano-Cuadrado, Yolanda, Gonzalo-Iglesias, Maria D., Lozano-Sanchez, Francisco S., Gomez-Alonso, Alberto
• Format: Journal Article
• Language: English
• Published: UK Taylor & Francis, Ltd 01.07.1999; Taylor & Francis
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Cell Movement - drug effects; Digestive system; Down-Regulation - drug effects; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Inflammation Mediators - metabolism; Ischemia - metabolism; Leukocytes - drug effects; Leukocytes - metabolism; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Medical sciences; Neutrophils - drug effects; Neutrophils - metabolism; Oligosaccharides - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric; Rat; Liver; Rodentia; Cytokine; Cardiovascular disease; Hepatic disease; Chemical mediator; Inflammation; Experimental study; Free radical; Vascular disease; Vertebrata; Mammalia; Ischemia; Animal; Digestive diseases; Neutrophil; Protection
• ISSN: 1102-4151; 1741-9271
• DOI: 10.1080/11024159950189762

Objective: To elucidate mechanisms of protection of ischaemic liver with the sialyl Lewis X analogue CY‐1503 by regulation of inflammatory mediators such as oxygen free radicals and cytokines as well as blocking the migration of leucocytes. Design: Laboratory study. Setting: Teaching hospital, Spain. Animals: 122 male Sprague‐Dawley rats divided into four groups: normal (n = 18), sham‐operated (n = 28), ischaemic controls (n = 38), and CY‐1503 (n = 38). Interventions: Warm total hepatic ischaemia for 90 minutes followed by various periods of reperfusion. Main outcome measures: Survival, liver histology, liver function, neutrophil infiltration, and free radical and cytokine concentrations. Results: 2/20 ischaemic controls survived, compared with 14/20 given CY‐1503. Liver function was better, as was histological appearance (judged by the Suzuki score); myeloperoxidase activity was significantly decreased (n = 6 in each group, p < 0.01) as were concentrations of free radicals (n = 12 in each group, p < 0.05) in the group given CY‐1503. CY‐1503 had no effect on concentrations of the cytokines tumour necrosis factor‐α or interleukin 1‐α. Conclusions: CY‐1503 exerts a protective effect in that it able to down‐regulate concentrations of free radicals in our rat model. It is a potent inhibitor of neutrophil migration, but has no effect on cytokine concentrations. Copyright © 1999 Taylor and Francis Ltd.