Evaluation of a New Venoactive Micronized Flavonoid Fraction (S 5682) in Symptomatic Disturbances of the Venolymphatic Circulation of the Lower Limb: A Double-Blind, Placebo-Controlled Study

Gilly, R; Pillion, G; Frileux, C

doi:10.1177/026835559400900206

Cited by 49 publications

(41 citation statements)

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“…Its antiedematous properties have been demonstrated in animals [1] and man [2]. Recently, experimental studies have been conducted to elucidate the mechanism of action of the compound and more specifically its effects on the microcirculation by intravital microscopy.…”

Section: Introductionmentioning

confidence: 99%

Leukocyte Adhesion after Oxidant Challenge in the Hamster Cheek Pouch Microcirculation

Bouskela

Cyrino²,

Lerond³

1999

J Vasc Res

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Oral administration of S-5682 (Daflon 500 mg, 90% diosmin, 10% hesperidin) inhibits oxidant-induced increase in macromolecular permeability in the postcapillary venules of the hamster cheek pouch microcirculation. In this study, the effect of S-5682 on leukocyte-endothelium interaction was evaluated using the same experimental model. Hamsters kept on a standard diet were divided into 5 groups (n = 6) and treated orally, twice a day, with placebo (10% lactose solution), S-5682, 5, 20 or 80 mg/kg/day (suspended in 10% lactose solution) or α-tocopherol, 1 mg/kg/day, for 10 days prior to the oxidant challenge with tert-butylhydroperoxide (TBOOH). Topical application of TBOOH (10^–4 M for 5 min) to hamsters given acridine orange prior to TBOOH resulted in increases in the number of rolling and sticking (no movement for at least 30 s) leukocytes in postcapillary venules. No changes in the number of rolling leukocytes could be observed in the treated groups compared with the placebo group (p > 0.05). On the contrary, leukocyte adhesion was inhibited in groups treated with S-5682 (5, 20 and 80 mg/kg/day) or α-tocopherol: placebo 105 ± 3/6 mm² (mean ± SEM); S-5682, 5 mg/kg/day 68 ± 3/6 mm² (p < 0.01), 20 mg/kg/day 55 ± 3/6 mm² (p < 0.001) and 80 mg/ kg/day 39 ± 2/6 mm² (p < 0.001) and α-tocopherol 36 ± 1/6 mm² (p < 0.001). The inhibition of oxidant-induced leukocyte adhesion by S-5682 was similar to that seen for ischemia-reperfusion and the higher dose of S-5682 was as effective as α-tocopherol in inhibiting it.

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Section: Introductionmentioning

confidence: 99%

Leukocyte Adhesion after Oxidant Challenge in the Hamster Cheek Pouch Microcirculation

Bouskela

Cyrino²,

Lerond³

1999

J Vasc Res

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“…Undoubtedly, Dafion® 500 mg has pro found phlebotropic activity [7,8]. The anti-edematous effects of Dafion® 500 mg may also become relevant under conditions in which increased permeability is found at the precapillary and capillary site of the microvascular network as observed in diabetic and/or hyperten sive retinopathies [9,10].…”

Section: Introductionmentioning

confidence: 99%

Effects of Daflon® 500 mg on Postischemic Macromolecular Leak Syndrome in Striated Skin Muscle of the Hamster

Nölte

Pickelman²,

Schütze³

et al. 1997

Int J Microcirc

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We have recently shown that the purified micronized flavonoid fraction (90% diosmin and 10% hesperidin) Daflon® 500 mg attenuates reperfusion injury in the striated skin muscle of the hamster. Herein, we report on the action of Daflon® 500 mg on postischemic macromolecular leakage of FITC-dextran 150 kD provoked by tourniquet ischemia. Intravital fluorescence microscopy was used for analysis of macromolecular leakage in the microcirculation model of the hamster. A tourniquet ischemia of 4 h duration was induced followed by reperfusion. Animals were treated by gavage of Daflon® 500 mg (n = 6) for 8 days at a daily dose of 30 mg kg-1 body weight. Control animals received equivalent volumes of the vehicle (5% Arabic gum solution, n = 6). Measurements of the microcirculatory parameters were made before induction of ischemia and at 0.5,2 and 24 h of reperfusion. After induction of ischemia, macromolecular leakage from postcapillary venules was significantly enhanced in vehicle-treated animals. Treatment with Daflon® 500 mg significantly attenuated macromolecular leakage of FITC-dextran 150 kD. Preliminary data from a histomorphometric analysis (n = 3/experimental group) indicated that the number of emigrated (extravascular) leukocytes after ischemia reperfusion was markedly reduced in Daflon® 500 mg-treated animals as compared to controls. These data indicate that Daflon® 500 mg prevents leakage of the macromolecular tracer FITC-dextran 150 kD from postcapillary venules after postischemic reperfusion, presumably through an inhibitory action on the emigration of activated leukocytes.

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“…Studies in patients with venous disease showed that leg edema was significantly reduced by S-5682 [1,2]. Studies in experimental animals have demonstrated that the histamine, bradykinin, leukotrienc B4 [3] and ischemia/reperfusion (I/R) [4]-induced increase in vascular permeability was inhibited by S-5682 given orally to hamsters for 10 days.…”

Section: Introductionmentioning

confidence: 99%

Oxidant-lnduced Increase in Vascular Permeability Is Inhibited by Oral Administration of S-5682 (Daflon® 500 mg) and Alpha-Tocopherol

1997

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The aim was to study the effect of oral administration of three different doses of S-5682 and α-tocopherol on an oxidant-induced injury by tert-butylhydroperoxide (TBOOH) resulting in increased plasma leakage from postcapillary venules in the hamster cheek pouch microcirculation. Hamsters were on a standard laboratory animal diet with normal vitamin E and C content. Five groups of hamsters (n = 6) were treated orally with placebo (10% lactose solution), S-5682 (5, 20 or 80 mg/kg/day) suspended in 10% lactose solution, or α-tocopherol (1 mg/kg/day) for 10 days prior to oxidant challenge with TBOOH. Topical application of 10^-4M TBOOH for 5 min to hamsters given FITC-dextran 30 min prior to TBOOH resulted in reversible increases in the number (mean ± SE) of leaks in postcapillary venules: placebo, 117 ± 7 leaks/ cm²; S-5682, 5 mg/kg/day, 68 ± 3 leaks/cm² (p < 0.01); S-5682,20 mg/kg/day, 41 ± 3 leaks/cm² (p < 0.01); S-5682, 80 mg/kg/day, 25 ± 2 leaks/cm² (p < 0.001), and α-tocopherol, 1 mg/kg/day, 18 ± 1 leaks/cm² (p < 0.001). The efficacy of inhibition of oxidant-induced leakage by S-5682 was similar to that seen with the same dose (20 mg/kg/day) of histamine, bradykinin, leukotriene B₄ or ischemia/reperfusion-induced leakage, suggesting a common pathway for the induction of plasma leakage by these mediators. The maximal dose of S-5682 (80 mg/kg/day) was as effective as α-tocopherol (1 mg/kg/day) in inhibiting plasma leakage.

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Evaluation of a New Venoactive Micronized Flavonoid Fraction (S 5682) in Symptomatic Disturbances of the Venolymphatic Circulation of the Lower Limb: A Double-Blind, Placebo-Controlled Study

Cited by 49 publications

References 0 publications

Leukocyte Adhesion after Oxidant Challenge in the Hamster Cheek Pouch Microcirculation

Leukocyte Adhesion after Oxidant Challenge in the Hamster Cheek Pouch Microcirculation

Effects of Daflon® 500 mg on Postischemic Macromolecular Leak Syndrome in Striated Skin Muscle of the Hamster

Oxidant-lnduced Increase in Vascular Permeability Is Inhibited by Oral Administration of S-5682 (Daflon® 500 mg) and Alpha-Tocopherol

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