Membrane lipid interactions in intestinal ischemia/reperfusion-induced Injury

Abstract

Ischemia, lack of blood flow, and reperfusion, return of blood flow, is a common phenomenon affecting millions of Americans each year. Roughly 30,000 Americans per year experience intestinal ischemia-reperfusion (IR), which is associated with a high mortality rate. Previous studies of the intestine established a role for neutrophils, eicosanoids, the complement system and naturally occurring antibodies in IR-induced pathology. Furthermore, data indicate involvement of a lipid or lipid-like moiety in mediating IR-induced damage. It has been proposed that exposure of neo-antigens are recognized by antibodies, triggering action of the complement cascade. While it is evident that the pathophysiology of IR-induced injury is complex and multi-factorial, we focus this review on the involvement of eicosanoids, phospholipids and neo-antigens in the early pathogenesis. Lipid changes occurring in response to IR, neo-antigens exposed and the role of a phospholipid transporter, phospholipid scramblase 1 will be discussed.

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids

“…It has been recently discovered that the increased LysoPCs may induce inflammation, apoptosis and cardiac contractile dysfunction in CVDs ( Chen et al, 1997 ; Xu et al, 2016 ). In general, LysoPCs and free acids (e.g., arachidonic acid) can be released through hydrolysis of the ester bond of PCs ( Slone and Fleming, 2014 ). In the present study, we also found that the alterations in PCs, which possessed anti-oxidation, anti-inflammation and anti-fibrosis activities.…”

Attenuation of endothelial phosphatidylserine exposure decreases ischemia-reperfusion induced changes in microvascular permeability

“…In models of hypoxia-reoxygenation, PS exposure is linked to IgM binding and promulgation of the inflammatory response [16]. In intestinal ischemia-reperfusion injury, PS exposure promotes intestinal hyperpermeability [17]. Transmembrane exposure of PS causes complement activation in vitro after hypoxia-reoxygenation, producing further inflammation and vascular injury [18].…”

Indole-TEMPO conjugates alleviate ischemia-reperfusion injury via attenuation of oxidative stress and preservation of mitochondrial function

“…4 Reperfusion of the superior mesenteric artery (SMA) induces activation of poly-morphonuclear neutrophils (PMNs), with accompanying release of pro-inflammatory substances and enhanced production of free radicals. 5,6 These radicals, including hydroxyl radicals, play a role in the pathophysiology of intestinal I/R injury by promoting lipid and DNA oxidation/peroxidation, enhanced free radical formation and associated mitochondrial depolarization, and eventually cellular apoptosis. Additionally, these pro-inflammatory factors activated following I/R injury circulate via both venous and lymphatic systems, inducing distant organ injury that contributes to both the systemic inflammatory response and acute respiratory distress syndromes that have been highlighted by multiple studies documenting the beneficial effects of interventions to mitigate ROS effects.…”

“…Additionally, these pro-inflammatory factors activated following I/R injury circulate via both venous and lymphatic systems, inducing distant organ injury that contributes to both the systemic inflammatory response and acute respiratory distress syndromes that have been highlighted by multiple studies documenting the beneficial effects of interventions to mitigate ROS effects. 5,6 A stable piperidine nitroxide, 4-hydroxy-TEMPO (TEMPOL) is a water-soluble intermediate widely employed in electron spin resonance spectroscopy. TEMPOL permeates biological membranes, accumulates in the cytosol, and scavenges superoxide anions in vitro, thus acting as a "SOD (superoxide dismutase)-mimetic".…”