s-5682 and Reperfusion-Injury

Inflammation activates leukocytes causing the release of agents that disrupt the endothelial barrier to such an extent that retention of plasma protein is impaired. This phenomenon can be observed using microvascular methods in which ischemia-reperfusion-induced inflammation-like condition are analyzed in terms of the increased adherence of leukocytes to the venular endothelium. Pretreatment with Daflon 500 mg, a purified, micronized, flavonoid fraction consisting of 90% diosmin and 10% hesperidin, prior to the induction of 4 h of tourniquet ischemia significantly lowers the number of adherent leukocytes. This observation is linked to the protective effect of flavonoids in the treatment of edema, as decreased activation is also associated with a decreased platelet and complement system activation, leading to a lowered release of histamine and decreased leukocyte-dependent endothelial damage. It is proposed that attenuation of leukocyte adherence during ischemia-reperfusion is evidence of the protective endothelial effect of Daflon 500 mg and its ability to control edema in clinical situation.

Topics: Animals; Diosmin; Drug Combinations; Edema; Flavonoids; Hesperidin; Inflammation; Leukocytes; Microcirculation; Reperfusion Injury; Skin

The effects of a clinically used purified micronized flavonoid fraction (S 5682) containing 90% diosmin and 10% hesperidin on increased microvascular permeability induced by histamine, bradykinin, and leukotriene B4 (LTB4) were investigated by intravital microscopy in the hamster cheek pouch preparation. The authors also investigated the effects of S 5682 on macromolecular permeability increase and leukocyte adhesion during ischemia-reperfusion by using the same preparation. S 5682, suspended in 10% lactose solution, or vehicle (10% lactose) was administered orally to male hamsters for ten days at 20 mg/kg/day (10 mg/kg twice a day). Fluorescein isothiocyanate (FITC)-labeled dextran (mol wt 150,000) was given intravenously, thirty minutes after completion of the cheek pouch preparation. The leukocytes were stained by continuous IV infusion of acridine orange (0.5 mg/kg/minute). Histamine (2 microM), bradykinin (1 microM), and LTB4 (0.01 microM), applied topically for five minutes, increased the number of fluorescent vascular leakage sites in postcapillary venules. A temporary ischemia with total circulatory arrest of the cheek pouch was obtained by clamping the neck of the everted pouch. The maximum number of leaky sites (per cm2 in the prepared area) that occurred either at five minutes after the beginning of each topical application or ten minutes after the onset of reperfusion was quantified in ultraviolet light microscopy. The results from 60 animals divided into 10 groups of 6 animals each are presented as means +/- SEM. In comparison with vehicle, S 5682 significantly inhibited the macromolecular permeability increasing effect of histamine (343.5 +/- 22.3 versus 207.5 +/- 32.0 leaks/cm2; P < 0.01), bradykinin (345.2 +/- 19.0 versus 206.2 +/- 21.6 leaks/cm2; P < 0.01), and LTB4 (353.3 +/- 27.5 versus 242.7 +/- 33.6 leaks/cm2; P < 0.05). At reperfusion, after thirty minutes of ischemia, S 5682 significantly decreased the observed macromolecular permeability (103.6 +/- 15.4 versus 42.6 +/- 9.3 leaks/cm2; P < 0.01). Flavonoid-treated animals also displayed a statistically significant lower number of adhering leukocytes to the venular endothelium (83.5 +/- 9.5 versus 48.4 +/- 12.3 per 6 mm2; P < 0.05). These results demonstrate that oral administration of S 5682 for ten days at 20 mg/kg body weight/day had a protective effect against leakage of macromolecules after application of permeability-increasing substances and during ischemia-reperfusion in the c

Topics: Administration, Oral; Animals; Capillary Permeability; Cell Adhesion; Cheek; Cricetinae; Diosmin; Drug Combinations; Flavonoids; Hesperidin; Leukocytes; Male; Reperfusion Injury

The effect of Daflon 500 mg1, purified, micronized flavonoid fraction (90% diosmin, 10% hesperidin) was studied on stroke index, levels of free radicals and electroretinography in the gerbil after ischemia-reperfusion injury. The drug was administered orally at doses of 200, 100 and 50 mg/kg, for 6 days before left carotid occlusion. Daflon 500 mg significantly reversed the increase of stroke index only at the dose of 100 mg/kg and significantly decreased levels of hydroxyl free radicals at all 3 doses with a maximum effectiveness for the dose of 100 mg/kg. Amplitude and latency of the b wave were disturbed after ischemia-reperfusion insult. Daflon 500 mg, 100 mg/kg for 6 days, significantly reversed these modifications. In conclusion, Daflon 500 mg could interact with hydroxyl free radicals, which have a deleterious effect in ischemic tissues, particularly in the retina.

Topics: Animals; Behavior, Animal; Brain Ischemia; Diosmin; Drug Combinations; Electroretinography; Female; Flavonoids; Free Radicals; Gerbillinae; Hesperidin; Lipid Peroxidation; Male; Reperfusion Injury; Retina