Leukocyte Adhesion after Oxidant Challenge in the Hamster Cheek Pouch Microcirculation

Abstract

Oral administration of S-5682 (Daflon 500 mg, 90% diosmin, 10% hesperidin) inhibits oxidant-induced increase in macromolecular permeability in the postcapillary venules of the hamster cheek pouch microcirculation. In this study, the effect of S-5682 on leukocyte-endothelium interaction was evaluated using the same experimental model. Hamsters kept on a standard diet were divided into 5 groups (n = 6) and treated orally, twice a day, with placebo (10% lactose solution), S-5682, 5, 20 or 80 mg/kg/day (suspended in 10% lactose solution) or α-tocopherol, 1 mg/kg/day, for 10 days prior to the oxidant challenge with tert-butylhydroperoxide (TBOOH). Topical application of TBOOH (10^–4 M for 5 min) to hamsters given acridine orange prior to TBOOH resulted in increases in the number of rolling and sticking (no movement for at least 30 s) leukocytes in postcapillary venules. No changes in the number of rolling leukocytes could be observed in the treated groups compared with the placebo group (p > 0.05). On the contrary, leukocyte adhesion was inhibited in groups treated with S-5682 (5, 20 and 80 mg/kg/day) or α-tocopherol: placebo 105 ± 3/6 mm² (mean ± SEM); S-5682, 5 mg/kg/day 68 ± 3/6 mm² (p < 0.01), 20 mg/kg/day 55 ± 3/6 mm² (p < 0.001) and 80 mg/ kg/day 39 ± 2/6 mm² (p < 0.001) and α-tocopherol 36 ± 1/6 mm² (p < 0.001). The inhibition of oxidant-induced leukocyte adhesion by S-5682 was similar to that seen for ischemia-reperfusion and the higher dose of S-5682 was as effective as α-tocopherol in inhibiting it.