Increased vascular permeability of
inflammation is accounted for by the formation/release of mediators, such as
lipids derived from arachidonate (
eicosanoids:
prostaglandins,
thromboxane A2 or
leukotrienes) or from
ether phospholipids (
PAF-acether). Acute
inflammation can be controlled by inhibitors of mediator synthesis or by antagonists, as well as at the level of the reactivity of vascular endothelium or leukocytes. This modulation can be obtained with
flavonoids, such as
S 5682, a precise fraction of
diosmin and
hesperidin, which reduces the vascular permeability of the rabbit skin and increases the resistance of rat microvessels. After chronic treatment by the oral route with
S 5682, the synthesis of
PGE2,
PGF2 and TxB2 decreased in inflammatory
granuloma in the rat, induced by introducing subcutaneously
polyurethane pellets. We carried out studies to see if
S 5682 modifies the amounts of TxB2, of
PGE2 and of PGI2 formed by perfused guinea-pig lungs injected with
PAF-acether (1-100 ng). At 5-50 microM,
S 5682 favoured the formation of
PGE2 and of
prostacyclin, and less that of
thromboxane. At higher concentrations, the stimulation of the formation of
eicosanoids was less marked, suggesting a biphasic effect. The biosynthetic profile of
eicosanoids was affected at low concentrations the
flavonoids with a complex and original pattern.