Abstract
A clinically available mixture of hydroxyethylrutosides (HR) was examined as a protector against endothelial cell activation by hypoxia in perfused human umbilical vein. The results showed that 500 μg/mL HR totally inhibited the adherence of human unstimulated neutrophils to the endothelium of umbilical vein incubated in hypoxic conditions. This inhibition was confirmed by a morphological study performed by scanning electron microscopy. In addition, neutrophils adherent to the hypoxic umbilical vein endothelium became activated, as evidenced by the increased release of superoxide anions and synthesis of leukotriene B4. These processes could also be inhibited by HR. In conclusion, the results of this study suggest that the improvement in venous insufficiency observed clinically with HR could, in part, be the result of their ability to inhibit the recruitment and activation of neutrophils by endothelium activated during blood stasis.
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References
Beaglehole R. Epidemiology of varicose veins.World J Surg 1986;10:898-902.
Arnould T, Michiels C, Alexandre I, Remacle J. Effect of hypoxia upon intracellular calcium concentration of human endothelial cells. J Cell Physiol 1992;152:215-221.
Michiels C, Arnould T, Knott I, Dieu M, Remacle J. Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. Am J Physiol 1993;264:C866-C874.
Michiels C, De Leener F, Arnould T, Dieu M, Remacle J. Hypoxia stimulates human endothelial cells to release smooth muscle cell mitogens: Role of prostaglandins and bFGF. Exp Cell Res 1994;213:43-54.
Arnould T, Michiels C, Remacle J. Increased PMN adherence on endothelial cells after hypoxia: Involvement of PAF, CD18/CD11b and ICAM-1. Am J Physiol 1993;264:C1102-C1110.
Arnould T, Michiels C, Remacle J. Hypoxic human umbilical vein endothelial cells induce activation of adherent polymorphonuclear leukocytes. Blood 1994;83:3705-3716.
Michiels C, Arnould T, Remacle J. Rôle-clé de l'hypoxie et des cellules endothéliales dans le développement des veines variqueuses. Med/Sci 1994;10:845-853.
Balmer A, Limoni C. A double-blind placebo-controlled clinical trial of Venoruton on the symptoms and signs of chronic venous insufficiency. The importance of patient selection Vasa 1980;9:76-82.
Pulvertaft TB. General practise treatment of symptoms of venous insufficiency with oxerutins. Results of a 660 patient multicentre study in the UK. Vasa 1983;12:373-376.
Neumann HAM, van den Broek MJTB. Evaluation of O-(β-hydroxyethyl)-rutosides in chronic venous insufficiency by means of non-invasive techniques. Phlebologie 1990;5(Suppl. 1): 13-20.
Poynard T, Valterio C. Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency. Vasa 1994;23:244-250.
Roztocil K, Prerovsky I, Oliva I. The effect of hydroxyethylrutosides on capillary filtration rate in the lower limb of man. Eur J Clin Pharmacol 1977;11:435-438.
Cesarone MR, Laurora G, Ricci A, Belcaro G, Candani C, Leon M, Nicolaides AN. Acute effects of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy. A dose comparison study. Vasa 1992; 21:76-80.
Gerdin B, Svensjo E. Inhibitory effect of the flavonoid O-(β-hydroxyethyl)-rutosides on increased microvascular permeability induced by various agents in rat skin. Int J Microcirculation 1983;2:39-46.
Kendall S, Towart R, Michel C. Effects of hydroxyethylrutosides on the permeability of microvessels in the frog mesentery. Br J Pharmacol 1993;110:199-206.
Rehn D, Hennings G, Nocker W, Diebschlag W. Time course of the anti-oedematous effect of O-(β-hydroxyethyl)-rutosides in healthy volunteers. Eur J Clin. Pharmacol 1991;40: 625-627.
Janssens C, Michiels C, Arnould T, Remacle J. Effects of hydroxyethylrutosides on hypoxia-induced activation of human endothelial cells in vitro. Br J Pharmacol 1996;118: 599-604.
Gimbrone MA. Hemodynamics, endothelial gene expression and atherogenesis. Ann N Y Acad Sci 1997;811:1-10.
Arnould T, Michiels C, Janssens D, Delaive E, Remacle J. Hypoxia induces PMN adherence to umbilical vein endothelium. Cardiovasc Res 1995;30:1009-1016.
Coleridge-Smith PD, Thomas P, Scurr JH, Dormandy JA. Causes of venous ulceration: A new hypothesis. Br Med J 1988;296:1726-1727.
Crotty TP. The origin and the progression of varicose veins. Med Hypotheses 1992;37:198-204.
NcEwan AJ, McArdle CS. Effect of hydroxyethylrutosides on blood oxygen levels and venous insufficiency symptoms in varicose veins. Br Med J 1971;2:138-141.
Michiels C, Arnould T, Janssens D, Bajou K, Géron I, Remacle J. Interactions between endothelial cells and smooth muscle cells after their activation by hypoxia. A possible etiology for venous disease. Int Angiol 1996;15:124-130.
Dittrich P, Ostrowski J, Beubler E, Schraven E, Kukovetz W. HPLC-bestimmng von troxerutin im plasma und harn nach oraler gabe am menschen. Arzneimittel-Forschung/Drug Res 1985;35:765-767.
Michiels C, Arnould T, Janssens D, Alexandre I, Houbion A, Remacle J. Effect of naftidrofuryl on hypoxia-induced activation and mortality of human endothelial cells. J Pharmacol Exp Ther 1993;267:904-911.
Arnould T, Michiels C, Janssens D, Remacle J. Effects of aescine on hypoxia-induced activation of human endothelial cells. Eur J Pharmacol 1996, 315:227-233.
Arnould T, Michiels C, Janssens D, Berna N, Remacle J. Effect of Ginkor Fort on hypoxia-induced neutrophil adherence to human saphenous vein endothelium. J Cardiovasc Pharmacol 1998;31:456-463.
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Roland, I.H., Bougelet, C., Ninane, N. et al. Effect of Hydroxyethylrutosides on Hypoxial-Induced Neutrophil Adherence to Umbilical Vein Endothelium. Cardiovasc Drugs Ther 12, 375–381 (1998). https://doi.org/10.1023/A:1007772817842
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DOI: https://doi.org/10.1023/A:1007772817842