Sulfo-LewisXDiminishes Neutrophil Infiltration and Free Radicals with Minimal Effect on Serum Cytokines after Liver Ischemia and Reperfusion

Abstract

cytes. One mechanism of accumulation is cell adhesion. Background: Cell adhesion plays a central role in The selectin family of adhesion molecules play a pivotal the pathogenesis of neutrophil-induced hepatic injury role in the leukocyte/endothelial cell events associated after ischemia and reperfusion. Sialyl Lewis x binds to with tissue inflammation and damage following ischselectins mediating neutrophil adherence to endothe-emia and reperfusion (I/R) [1][2][3][4]. Previous in vitro and lium, thereby facilitating subsequent migration and in vivo studies have clearly implicated neutrophil mitissue damage. Aim: We studied the effect of a novel gration as one of the key mechanisms involved in hesulfo-derivative of sialyl Lewis x , GM-1998, on the liver patic I/R injury [5][6][7][8].inflammatory response after ischemia and reperfu-P-and E-selectin, expressed on the activated vassion. Specifically, we evaluated its impact on three key cular endothelium following I/R, mediate neutrophil inflammatory mediators: neutrophil migration, free adhesion at sites of tissue injury and inflammation radicals, and serum cytokines. Material and methods: [9 -12] In this study, we investigated the effect of a glya), and liver histology were analyzed 4 hr after reperfusion. Additionally, survival was followed for up to 7 comimetic [17, 18], novel sulfo-derivative of sialyl days. Results: Seven-day survival significantly in-Lewis x , GM-1998, in an in vivo model of liver I/R. We creased from 20% in the control group to 65% in the hypothesized that this synthetic glycomimetic could sulfo-Lewis x treated group. Liver function tests and compete against the natural sialyl Lewis x ligand for histological damage scores were improved in compari-the selectin receptor, thereby blocking selectin-medison to controls. We observed significant downregula-ated neutrophil adhesion. In addition, we explored tion of free radicals and neutrophil migration. This the effects of GM-1998 on the regulation of two other compound did not significantly affect serum cytokine key inflammatory mediators, free radicals and serum levels. Conclusions: GM-1998 showed a protective ef-cytokines (specifically IL-1 and TNF-a levels), in livfect in an in vivo model of severe liver ischemia and ers subjected to I/R. reperfusion by decreasing tissue free radical levels and selectin-mediated neutrophil migration. This pro-MATERIAL AND METHODS tective effect was also reflected in improved liver function tests and histological response leading to better survival. We confirmed the beneficial effect of neutroOne hundred and fifty male Sprague-Dawley rats (Charles River Breeding Laboratories, Inc., Portage, MI), weighing 250-275 g, were phil blockade as a key target to prevent damage after fasted for 12 hr before surgery and allowed water ad libitum. Rats the reperfusion phenomenon by using a glycomimetic were anesthetized with Ketamine hydrochloride (Ketalar, Parke-

Effects of Ascorbic Acid, Alpha-Tocopherol and Allopurinol on Ischemia-Reperfusion Injury in Rabbit Skeletal Muscle: An Experimental Study

“…Through this, it prevents the formation of OH − radicals, which are more toxic. Criado found that CAT enzyme levels increased in 30 minutes after I/R damage (47). For GPx catalyses H 2 O 2 and lipid hydroperoxidase, it protects to cellular membranes from damage, prevents the start and development of lipid peroxidation.…”

Effect of ONO-4057 and tacrolimus on ischemia-reperfusioninjury of the liver

“…Neutrophils are mainly responsible for the physiopathological changes that occur after ischemia-reperfusion injury [1][2][3] . These cells are markedly activated when the ischemically damaged liver is transplanted.…”

Respuesta inflamatoria y cirugía protésica. Su control con donadores de óxido nítrico

“…En nuestro estudio, la menor expresión detectada en ICAM-1, VCAM-1 y PECAM-1 determinará una menor interacción leucocito-endotelio y consecuentemente una menor infiltración neutrofílica, aspecto éste directamente relacionado con el daño en la respuesta inflamatoria; a su vez la menor activación e infiltración neutrofílica conducirá a una menor producción de radicales libres del oxígeno causantes de lesión tisular, éstos a su vez, como mediadores inflamatorios de primer orden, tienen la capacidad de activar factores transcripcionales como NFκB responsable, como vimos en apartados anteriores, de la producción de diferentes citocinas proinflamatorias como el TNF-α, la IL-1 y el INF-γ responsables del incremento de la expresión de CAMs (295) y en el caso del TNF-α del incremento de producción de RLO. Todo ello redundará en una menor lesión tisular con un mantenimiento de la función del órgano y consecuentemente una menor morbi-mortalidad (70,95,97,277) .…”