Protective Effects of Polysaccharide Fucoidin on Myocardial Ischemia-Reperfusion Injury in Rats

Omata, M; Matsui, Naoko; Inomata, Norio; Ohno, Tomochika

doi:10.1097/00005344-199712000-00003

Cited by 61 publications

(45 citation statements)

References 49 publications

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“…Several studies have demonstrated that intestinal ischemi a! reperfusion injury in rats is dependent on neutrophil recruitment (25)(26)(27)(28)(29)(30)(31). Postischemic treatment of animals with reparixin inhibited the increase of vascular permeability and neutrophil recruitment in a dose-dependent manner (23).…”

Section: Lps-induced Blood Neutrophilia In Rats Four Hours After Lmentioning

confidence: 99%

Reparixin, a Specific Interleukin-8 Inhibitor, Has No Effects on Inflammation during Endotoxemia

Leitner

Mayr

Firbas

et al. 2007

Int J Immunopathol Pharmacol

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Reparixin antagonizes interleukin-8 (IL-8) on the level of signal transduction in vitro. We hypothesized that IL-8 mediates some of the reactions occurring during acute inflammation and specifically that IL-8 may be a mediator of endotoxin induced neutrophilia. We therefore tested the effects of reparixin on humoral and cellular parameters in LPS-induced acute systemic inflammation. The study is a randomized (3:2 active:placebo), double-blind, placebo-controlled parallel group trial. Twenty healthy male volunteers randomly received either reparixin (12) or placebo (8) intravenously. One hour after the start ofreparixin/placebo infusion a bolus of2 ng/kg endotoxin was infused over t-2 min. Blood samples were obtained over 24 h. Reparixin, being metabolized to ibuprofen, suppressed serum thromboxane 82 levels by 78% compared to baseline and control at 8 h. LPS-induced neutrophilia was not significantly affected by reparixin in human volunteers. Consistently, reparixin did not alter the lymphocyte or monocyte counts and had no effect on LPS-induced systemic inflammation as measured by tumor necrosis factor alpha (TNF-a) or interleukin-6 (IL-6) release. Regulation of IL-8 receptors CXCRt and 2 and the degranulation marker CDllb showed the expected kinetics. Reparixin had no effect on thrombin formation as measured by prothrombin fragment (F 1 + 2 ) . In conclusion, our study showed that reparixin was safe but had no impact on endotoxin induced inflammation. In contrast to previous studies with its metabolite ibuprofen, reparixin does not enhance inflammation in this model.Reparixin is a small molecule, which is structurally related to the known anti-inflammatory drug ibuprofen. It was developed as a novel, potent and specific inhibitor of the chemokine interleukin-8 (IL-8) on the level of intracellular signal transduction (1). Reparixin acts as a noncompetitive allosteric inhibitor of IL-8 receptors (CXCRI/2) which, by locking CXCR1I2 in an inactive conformation, prevents receptor signalling and human polymorphonuclear leukocyte (PMN) chemotaxis. IL-8 is responsible for several reactions occurring during acute inflammation and is able to induce neutrophilia (2-3). In particular, IL-8 infusion markedly increases neutrophil counts in non-human primates (2). Interleukin-8 induced neutrophilia results from demargination or by a release of neutrophils from bone marrow (3). In circulating monocytes, IL-6 and IL-8 induce tissue factor

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Section: Lps-induced Blood Neutrophilia In Rats Four Hours After Lmentioning

confidence: 99%

Reparixin, a Specific Interleukin-8 Inhibitor, Has No Effects on Inflammation during Endotoxemia

Leitner

Mayr

Firbas

et al. 2007

Int J Immunopathol Pharmacol

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“…Fucoidan, a sulfated polyfucose polysaccharide found in the extracellular matrix of brown algae, exhibits biological properties, including antithrombotic, 1) antiinflammatory, [2][3][4] antiviral, 5,6) anti-adhesive, 7) and antitumor [8][9][10] activities, and it plays a role in modulating host immune systems, 11) arresting the cell cycle, and inducing apoptosis. 12) Recently, it was found that intraperitoneal injection and venous injection of fucoidan can rapidly mobilize hematopoietic stem/progenitor cells with long-term potential to repopulate the bone marrow in mice and monkeys.…”

mentioning

confidence: 99%

Development of a Fucoidan-Specific Antibody and Measurement of Fucoidan in Serum and Urine by Sandwich ELISA

Tokita

Nakajima

Mochida

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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Fucoidan exhibits various biological properties. We raised a novel antibody against fucoidan extracted from Cladosiphon okamuranus and developed a sandwich ELISA method to measure fucoidan. The fucoidan antibody was specific and did not cross-react with other polysulfated polysaccharides. Fucoidan recovery from serum and urine by ELISA was 86-113%. Intra-and inter-assay CVs were 1.5-13.4%. Assay linearity was maintained after 3-fold dilution of each sample with phosphate-buffer saline (PBS). In the serum and urine of healthy volunteers (n ¼ 10), fucoidan was not detected before administration, and the levels markedly increased 6 and 9 h after oral administration. The molecular weight of the serum fucoidan determined by HPLC gel filtration remained unchanged, whereas that of urine fucoidan was significantly reduced. This is the first ELISA method of measuring serum and urine fucoidan levels after oral administration. The method is simple, reliable, and practical for the analysis of samples, especially urine samples.

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“…The vegetation-to-background uptake ratio was 5.2 (2.7-9.1). On autoradiography, the 99m Tc-fucoidan uptake ratio was 17 (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Coregistration of autoradiography with histologic analysis performed after routine staining of tissue slices showed a clear delineation of the tracer uptake within the vegetations (Supplemental Fig.…”

Section: Endocarditic Vegetationsmentioning

confidence: 97%

“…Moreover, its pharmacologic effect as an in vivo selectin inhibitor has been assessed in various models of ischemia-reperfusion. After transient myocardial ischemia, fucoidan administration was associated with a decrease of neutrophil infiltration and pla-telet deposition in reperfused myocardium and finally reduced the extent of necrosis (16,17).…”

mentioning

confidence: 93%

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

Rouzet

Bachelet-Violette

Alsac³

et al. 2011

J Nucl Med

116

107

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P-selectin expression is involved in the pathophysiology of biologically active arterial thrombus and endothelial activation after a transient ischemic event. Fucoidan is a polysaccharidic ligand of P-selectin, with a nanomolar affinity. In the present study, we propose a new approach of P-selectin molecular imaging based on radiolabeled fucoidan. Methods: Two kinds of experimental models were selected to evaluate the ability of radiolabeled fucoidan to detect P-selectin expression: plateletrich arterial thrombi (vegetations of infective endocarditis and arterial mural thrombus) and myocardial ischemia-reperfusion. These 2 settings were chosen because they were clinically relevant, and both were associated with an important overexpression of platelet and endothelial P-selectin, respectively. Results: 99m Tc-fucoidan SPECT was able to detect the presence of platelet-rich arterial thrombi in all animals, with a median target-to-background ratio of 5.2 in vegetations of endocarditis and 3.6 in mural aneurysmal thrombus, and to detect a persistent endothelial activation at 2 h after reperfusion. In this latter model, the magnitude of the signal was correlated with the extent of myocardium that underwent transient ischemia. The sensitivity of selectivity of the uptake and retention of 99m Tc-fucoidan in both settings was excellent. Conclusion: This study supports 99m Tc-fucoidan as a relevant imaging agent for in vivo detection of biologic activities associated with P-selectin overexpression, such as arterial thrombus and ischemic memory. Given the reported wide availability at a low cost, and its low toxicity, fucoidan seems to overcome some of the limitations of previous P-selectin-targeted imaging agents.Key Words: P-selectin; fucoidan; thrombus; ischemia; imaging J Nucl Med 2011; 52:1433-1440 DOI: 10.2967/jnumed.110.085852 P-sel ectin is an adhesion molecule expressed at the surface of endothelial cells and platelets on activation. It mediates leukocyte rolling on activated endothelium (1) and leukocyte trapping on platelet aggregates (2), through the interaction with its counterreceptor P-selectin glycoprotein ligand 1. In the cardiovascular field, P-selectin expression is involved in the pathophysiology of 2 settings of prominent clinical relevance: the renewal and growth of biologically active (at risk) arterial thrombus (2) and endothelial activation after an acute transient myocardial ischemic event referred to as ischemic memory (3). Activated platelets expose granular P-selectin on their membrane surface, and myocardial injury is associated with activation of endothelial cells resulting in Weibel-Palade bodies exocytosis and overexpression of adhesion molecules (1,4), which persists after ischemia has resolved. Therefore, P-selectin promotes platelet, endothelium, and leukocyte interactions, whatever the cardiovascular events, representing an important molecular target in acute and in chronic cardiovascular diseases.Consequently, many efforts have been made to develop imaging agents targeting P-selectin (5...

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Protective Effects of Polysaccharide Fucoidin on Myocardial Ischemia-Reperfusion Injury in Rats

Cited by 61 publications

References 49 publications

Reparixin, a Specific Interleukin-8 Inhibitor, Has No Effects on Inflammation during Endotoxemia

Reparixin, a Specific Interleukin-8 Inhibitor, Has No Effects on Inflammation during Endotoxemia

Development of a Fucoidan-Specific Antibody and Measurement of Fucoidan in Serum and Urine by Sandwich ELISA

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

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