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

Abstract

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.

Leukocyte Adhesion after Oxidant Challenge in the Hamster Cheek Pouch Microcirculation

“…S-5682 improved all the parameters measured in a dose-dependent fashion [7]. Finally, it was also possible to demonstrate that S-5682 dose-dependently inhibited the macromolecular permeability increase after an oxidant challenge elicited by tertbutylhydroperoxide (TBOOH) [8]. These results led us to think that the effects of S-5682 could be due to an antioxidant activity.…”

Benefit of a 2-Month Treatment with a Micronized, Purified Flavonoidic Fraction on Venous Ulcer Healing

“…20-80 mg/ kg/day) has been shown to have a beneficial effect on several of these events. A decrease in white blood cell sticking, elicited by reperfusion following ischaemia, was demonstrated in rat cremaster muscle and mesen tery [20] and in hamsters using either a skinfold cham ber model [21] or a cheek pouch model [22], A striking reduction in capillary hyperpermeability was observed in normoglycaemic hamsters using a skinfold chamber model [23], and in normoglycaemic [24] and diabetic hamsters [25] using a cheek pouch model as well as in rat cremaster [26], after either reperfusion following ischaemia [24][25][26] or application of proinflammatory substances: bradykinin [24][25][26], leukotriene B4 and his tamine [24,25], A dose-dependent inhibition of oxi dant-induced vascular permeability could be observed in the hamster cheek pouch model [27],…”

Biological Properties of Citrus Flavonoids Pertaining to Cancer and Inflammation

“…In addition to inhibiting the synthesis of arachidonic acid-derived mediators during inflammation, Daflon 500 mg was further shown to inhibit the microvascular permeability increases induced by a number of other inflammatory mediators [38][39][40][41]. Oral administration of Daflon 500 mg at 10 and 20 mg Kg -1 twice daily significantly inhibited the permeability increasing effect of bradykinin, histamine, and leukotriene B 4 topically applied to the cheek pouches of normal and diabetic hamsters [39,40].…”

“…Oral administration of Daflon 500 mg at 10 and 20 mg Kg -1 twice daily significantly inhibited the permeability increasing effect of bradykinin, histamine, and leukotriene B 4 topically applied to the cheek pouches of normal and diabetic hamsters [39,40]. Diosmin and hesperidin were also effective in decreasing the microvascular hyperpermeability induced by the oxidative injury caused by ischemia/reperfusion of rat cremaster muscle and hamster cheek pouch tissue [35,38,[40][41][42][43].…”