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

Abstract

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.

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],…”

Clinical Use of Micronized Purified Flavonoid Fraction for Treatment of Symptoms After Hemorrhoidectomy: Results of a Randomized, Controlled, Clinical Trial

“…28,29 This protective effect on capillary fragility may prevent postoperative bleeding. In addition, MPFF increases lymphatic drainage 30,31 and protects the microcirculation from inflammatory mediators, [32][33][34][35] resulting in reduced edema and pain. This "edema-protective" effect of the drug may have a favorable influence on postoperative symptoms.…”

Experimental Models To Investigate Inflammatory Processes in Chronic Venous Insufficiency

“…If recurrent bouts of ischemia and reperfusion occur in venous disease, the stage would be set for the leukocyte infiltration that is one of the hallmarks of the disorder. The fact that venotonic drugs, such as micronized, purified flavonoid fraction (MPFF), Daflon 500 mg, Servier, France, are effective in the clinical management of chronic venous insufficiency and venous ulceration and exert powerful anti-inflammatory effects in the setting of I/R (irrespective of whether ischemia is produced by arterial or venous occlusion) (18,21,28,29,37,49) lend additional support to the potential involvement of I/R-induced leukocyte recruitment as a causative factor in CVI.…”