MEDIATORS INVOLVED IN INFLAMMATION - EFFECTS OF DAFLON 500MG ON THEIRRELEASE

Each step of an inflammatory reaction is triggered by one or several c hemical or biological mediators such as arachidonic acid derivatives ( prostaglandins [PG], leukotrienes [LT], or thromboxanes [TX]), vasoact ive amines (histamine or serotonin), and oxygen free radicals (superox ide ion, O2-, or hydrogen peroxide, H2O2). In perivenous inflammation, these mediators play a prominent role in favoring vasodilatation (his tamine), increasing membrane permeability (PGE2, histamine, free radic als) and providing a chemotactic signal for specialized cells, ie, neu trophil polynuclears, macrophages, lymphocytes (LTB4, free radicals). The antinflammatory effects of Daflon 500 mg, a micronized purified f lavonoid fraction (90% diosmin, 10% hesperidin), were studied in diffe rent in vivo and in vitro models. In a model of inflammatory granuloma in the rat, Daflon 500 mg (100 mg/kg, orally) reduced edema formation and inhibited the synthesis for PGE2 (78.5%), PGF2alpha (45.2%) and T XB2 (59.5%) (Damon et al, Arzneim-Forsch/Drug Res 37:1149-1153, 1987). Intravenous injection of Daflon 500 mg (25 and 50 mg/kg) reduced the hyperglycemia induced by injection of alloxan in rat. This effect of D aflon 500 mg was linked to its ability to scavenge active oxygen radic als, demonstrated in vitro using human neutrophils (Lonchampt et al, A rzneim-forsch/Drug Res 39:882-885, 1989) or mouse peritoneal macrophag es (Bodinier et al, manuscript in preparation) stimulated by zymosan. The free radical scavenger effect of Daflon 500 mg is observed at conc entrations ranging from 10(-7)M to 10(-4)M, with half-maximal effect b etween 10(-6)M and 10(-5)M. Thus, Daflon 500 mg behaves as a potent pr otective agent against inflammatory disorders. These properties, demon strated both in vivo and in vitro, justify its