title: Effects of Daflon 500 mg on increased microvascular permeability in normal hamsters.
abstract: Daflon 500 mg1 (S 5682) is a purified, micronized, flavonoid fraction containing 90% diosmin and 10% hesperidin, which is currently used to treat chronic venous insufficiency and haemorrhoidal disease. In the present study, the effects of Daflon 500 mg on increased microvascular permeability induced by histamine, bradykinin and leukotriene B4 (LTB4) were investigated by intravital microscopy in the hamster cheek pouch preparation. Daflon 500 mg, suspended in 10% lactose solution, or vehicle (10% lactose) was administered orally to male hamsters for 10 days at a dose of 20 mg/kg/day (10 mg/kg twice daily). Fluorescein isothiocyanate-labeled dextran 150 was given intravenously, 30 min after completion of the cheek pouch preparation. Histamine, 2 mumol/l, bradykinin, 0.1 mumol/l, and LTB4, 0.01 mumol/l, applied topically for 5 min increased the number of fluorescent vascular leakage sites in postcapillary venules. The maximum number of leaky sites per cm2 in the prepared area that occurred 5 min after the beginning of each topical application was quantified by UV light microscopy. In comparison with vehicle, Daflon 500 mg significantly inhibited the macromolecular permeability-increasing effect of histamine (343.5 +/- 22.3 vs. 207.5 +/- 32.0; p < 0.01), bradykinin (345.2 +/- 19.0 vs. 206.2 +/- 21.6; p < 0.01) and LTB4 (353.3 +/- 27.5 vs. 242.7 +/- 33.6; p < 0.05). These results demonstrate that oral administration of Daflon 500 mg for 10 days at 20 mg/kg body weight/day has a protective effect against leakage of macromolecules after application of permeability-increasing substances in the cheek pouch microvasculature. These data, which illustrate the inhibitory effect of a clinically relevant dose of Daflon 500 mg on the inflammatory processes induced in this in vivo model of microcirculation, may serve as a rational basis to explain the clinical efficacy of Daflon 500 mg.
authors: Department of Physiology and Biophysics, University of Lund, Sweden.
authors: E
authors: E
authors: Bouskela
authors: K A
authors: KA
authors: Donyo
authors: T J
authors: TJ
authors: Verbeuren
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D004145:Diosmin / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D005419:Flavonoids / Q000494:pharmacology*; D006569:Hesperidin / Q000008:administration & dosage / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male
chemical_list: D004338:Drug Combinations; D005419:Flavonoids; C080675:S 5682; D007975:Leukotriene B4; D004145:Diosmin; D006632:Histamine; D006569:Hesperidin; D001920:Bradykinin