The aim was to study the effect of oral administration of three different doses of S-5682 and alpha-tocopherol on an oxidant-induced injury by tert-butylhydroperoxide (TBOOH) resulting in increased plasma leakage from postcapillary venules in the hamster cheek pouch microcirculation. Hamsters were on a standard laboratory animal diet with normal vitamin E and C content. Five groups of hamsters (n = 6) were treated orally with placebo (10% lactose solution), S-5682 (5, 20 or 80 mg/kg/day) suspended in 10% lactose solution, or alpha-tocopherol (1 mg/kg/day) for 10 days prior to oxidant challenge with TBOOH. Topical application of 10(-4) M TBOOH for 5 min to hamsters given FITC-dextran 30 min prior to TBOOH resulted in reversible increases in the number (mean +/- SE) of leaks in postcapillary venules: placebo, 117+/-7 leaks/cm2; S-5682, 5 mg/kg/day, 68+/-3 leaks/cm2 (p < 0.01); S-5682, 20 mg/kg/day, 41+/-3 leaks/cm2 (p < 0.01); S-5682, 80 mg/kg/day, 25+/-2 leaks/cm2 (p < 0.001), and alpha-tocopherol, 1 mg/kg/day, 18+/-1 leaks/cm2 (p < 0.001). The efficacy of inhibition of oxidant-induced leakage by S-5682 was similar to that seen with the same dose (20 mg/kg/day) of histamine, bradykinin, leukotriene B4 or ischemia/reperfusion-induced leakage, suggesting a common pathway for the induction of plasma leakage by these mediators. The maximal dose of S-5682 (80 mg/kg/day) was as effective as alpha-tocopherol (1 mg/kg/day) in inhibiting plasma leakage.
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Bouskela et al. (2008) studied this question.