Leukocyte adhesion after oxidant challenge in the hamster cheek pouch microcirculation

Oral administration of S-5682 (Daflon 500 mg, 90% diosmin, 10% hesperidin) inhibits oxidant-induced increase in macromolecular permeability in the pos tcapillary venules of the hamster cheek pouch microcirculation. In this stu dy, the effect of S-5682 on leukocyte-endothelium interaction was evaluated using the same experimental model. Hamsters kept on a standard diet were d ivided 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% lac tose solution) or alpha-tocopherol, 1 mg/kg/day, for 10 days prior to the o xidant challenge with tert-butylhydroperoxide (TBOOH). Topical application of TBOOH (10(-4) M for 5 min) to hamsters given acridine orange prior to TB OOH resulted in increases in the number of rolling and sticking (no movemen t for at least 30s) leukocytes in postcapillary venules. No changes in the number of rolling leukocytes could be observed in the treated groups compar ed with the placebo group (p > 0.05). On the contrary, leukocyte adhesion w as inhibited in groups treated with S-5682 (5, 20 and 80 mg/kg/day) or alph a-tocopherol: placebo 105 +/- 3/6 mm(2) (mean +/- SEM); S-5682, 5 mg/kg/day 68 +/- 3/6 mm(2) (p < 0.01), 20 mg/kg/day 55 +/- 3/6 mm(2) (p < 0.001) and 80 mg/ kg/day 39 +/- 2/6 mm(2) (p < 0.001) and alpha-tocopherol 36 +/- 1/6 mm(2) (p < 0.001). The inhibition of oxidant-induced leukocyte adhesion by S-5682 was similar to that seen for ischemia-reperfusion and the higher do se of S-5682 was as effective as alpha-tocopherol in inhibiting it.