The effects of inhibiting leukocyte migration with fucoidin in a rat peritonitis model

Linnemann, G.; Reinhart, Konrad; Parade, Ulli; Philipp, Alois; Pfister, W.; Straube, E; Karzai, Waheedullah

doi:10.1007/s001340000642

Cited by 20 publications

(13 citation statements)

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“…14 HMW fucoidan reduces in vivo neutrophil adhesion and leukocyte migration. 33,34 Our recent data indicate that sulfated polysaccharides, including fucoidan, inhibit the release of proinflammatory cytokines/chemokines by activated monocytes, 35 which may be relevant for the inhibition of intimal hyperplasia. 36 (3) We and other groups have described that HMW and LMW fucoidans have antithrombotic activities and reduce platelet aggregation, an important stimulus of restenosis.…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Deux

Meddahi‐Pellé

Blanche

et al. 2002

ATVB

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Objective-Smooth muscle cell (SMC) proliferation within the intima is regulated by heparan sulfates. We studied a low molecular weight (LMW) fucoidan (sulfated polysaccharide from brown seaweed) on SMC proliferation in vitro and intimal hyperplasia in vivo. Methods and Results-In vitro study revealed that LMW fucoidan reduces rabbit SMC proliferation and is internalized in SMC perinuclear vesicles. On rabbit iliac arteries perfused in vivo with fluorolabeled LMW fucoidan after angioplasty, the labeling was mainly located on sites of injury. Pharmacokinetic studies showed that LMW fucoidan exhibited in rats an elimination half-life of 56Ϯ25 minutes (nϭ8) after intravenous administration and a constant plasma rate for Ն6 hours after intramuscular administration. After stent implantation in their iliac arteries, rabbits were also treated with LMW fucoidan (5 mg/kg IM twice a day Key Words: fucoidan Ⅲ hyperplasia Ⅲ restenosis Ⅲ stent Ⅲ vascular smooth muscle cell proliferation I ntimal hyperplasia due to migration and proliferation of smooth muscle cells (SMCs) from the media to the intima is a major component of restenosis after stent implantation. 1,2 Polysaccharides constitute a large family of molecules capable of developing molecular interactions with cellular targets within the arterial wall. 3 For instance, heparin, a natural sulfated polysaccharide, displays pleiotropic effects independent of the anticoagulant activity, including SMC growth inhibition, 4 anti-inflammatory activity, 5 and growth factor protection. 6 Fucoidan is a sulfated polysaccharide extracted from brown seaweed that reduces rat SMC proliferation in vitro in a more intensive manner than heparin. 7 We recently succeeded in producing and characterizing new homogeneous fractions of low molecular weight (LMW) fucoidan with low anticoagulant activity.The aims of the present study were to investigate the ability of LMW fucoidan to regulate vascular SMCs. For this purpose, we first tested the ability of LMW fucoidan to inhibit rabbit SMC proliferation in vitro. We explored the pharmacokinetics of LMW fucoidan injected in rats and the effect of LMW fucoidan on intimal hyperplasia. The results described below indicate that LMW fucoidan is a strong inhibitor of intimal hyperplasia and may be potentially relevant for the treatment of in-stent restenosis. Methods PolysaccharidesLMW fucoidan was isolated and hydrolyzed by a radical depolymerization process 8 from high molecular weight (HMW) extracts of brown marine algae. The characteristics of LMW fucoidan according to previously reported analytical methods 9 are as follows: weightaverage molecular mass 8Ϯ1 kDa; fucose content 35% (wt/wt); uronic acid content 3% (wt/wt); and sulfate content 34% (wt/wt). The anticoagulant activity in vitro of the LMW fucoidan was measured by an activated partial thromboplastin time (APTT), and the amount of LMW fucoidan required to obtain an APTT of 80 seconds (control 40 seconds) was 25 g/mL. 10 The anticoagulant activity in vivo of LMW fucoidan was measured in rabbit...

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Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Deux

Meddahi‐Pellé

Blanche

et al. 2002

ATVB

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“…We observed a significant reduction in nitric oxide (Machiavell et al, 2007) production in the presence of high fucan concentrations (above 375 µg/mL). However, we found a bifunctional effect (Yang et al, 2006;Di Rosa et al, 1996), given that low fucan concentrations Like heparin, fucoidans have been shown to affect many biological activities, such as inflammation, cell proliferation and adhesion, viral infection, and fertilization (Linnemann et al, 2000). However, relatively few studies have interpreted the biological activity of fucoidans in terms of molecular structure (Xie et al, 2000).…”

Section: Measurement Of Nomentioning

confidence: 75%

Sulfated fucans extracted from algae Padina gymnospora have anti-inflammatory effect

Marques¹,

Azevedo²,

Nascimento³

et al. 2012

Rev. bras. farmacogn.

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Sulfated polysaccharides were extracted with acetone from brown algae Padina gymnospora. The fraction precipitated with 1.5 volumes of acetone (F1.5) purified in Sephadex G-75 was characterized by infrared and nuclear magnetic resonance of 13 C and 1 H, through which the presence of sulfate groups on the C4 of α-L-fucose could be observed. This polysaccharide showed that an MW of 25,000 Da was effective in reducing leukocyte influx into the peritoneal cavity in mice at 10 mg/kg and 25 mg/kg body weight, causing a decrease of 60 and 39%, respectively. In the present study, it was observed that this fucan has anti-inflammatory properties but no cytotoxic action, indicating its potential use in the pharmaceutical industry.

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“…9 Several reports have revealed the anti-inflammatory effect of fucoidan against ischemicÀreperfusion myocardial injury, hypoxicÀischemic brain injury, and peritonitis via inhibition of selectin-mediated extravascular transmigration of inflammatory cells. [10][11][12] These findings have indicated the therapeutic potential of fucoidan on acute myocarditis. Thus, the purpose of this study was to investigate the in vivo effect of fucoidan treatment on rat EAM.…”

Section: Introductionmentioning

confidence: 92%

Sulfated Polysaccharide Fucoidan Ameliorates Experimental Autoimmune Myocarditis in Rats

Tanaka

Ito

Kodama

et al. 2010

J Cardiovasc Pharmacol Ther

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Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of experimental autoimmune myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidan binds selectin nonselectively and blocks its function. Therefore, this study was designed to evaluate whether in vivo fucoidan treatment can improve EAM. A 21-day infusion of physiological saline or fucoidan was administrated intraperitoneally to the rats with sham operation (sham-saline, n = 5; sham-fucoidan, n = 6) or those with cardiac myosin injection (EAM-saline, n = 10; EAM-fucoidan, n = 10). After 3 weeks, fucoidan treatment improved left ventricular ejection fraction (79.04 ± 2.81 vs 65.94% ± 3.22%; P < .01 vs EAM-saline) with a reduced ratio of heart weight to body weight (4.016 ± 0.239 vs 4.975 ± 0.252 mg/g; P < .05 vs EAM-saline) in EAM. Furthermore, fucoidan treatment decreased serum levels of BNP (292.0 ± 53.4 vs 507.4 ± 89.2 ng/mL; P < .05 vs EAM-saline) and the myocarditis area (31.66 ± 1.53 vs 42.51% ± 3.24%; P < .01 vs EAM-saline) in EAM. These beneficial effects of fucoidan were accompanied by inhibition of both macrophage and CD4-positive T-cell infiltration into the myocardium. Fucoidan, a nonselective selectin blocker, attenuates the progression of EAM. This observation may be explained, at least in part, by blocking the extravasation of inflammatory cells into the myocardium.

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The effects of inhibiting leukocyte migration with fucoidin in a rat peritonitis model

Cited by 20 publications

References 13 publications

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Sulfated fucans extracted from algae Padina gymnospora have anti-inflammatory effect

Sulfated Polysaccharide Fucoidan Ameliorates Experimental Autoimmune Myocarditis in Rats

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