THE EFFECT OF ERDOSTEINE AND ITS ACTIVE METABOLITE ON REACTIVE OXYGEN SPECIES PRODUCTION BY INFLAMMATORY CELLS

Objective: We examined the effect of erdosteine (KW-9144), an expectorant, and related compounds on inflammatory cell-derived reactive oxygen species which are involved in airway inflammation.¶Methods: Neutrophils were isolated from peritoneal lavages of casein-injected rats and from peripheral blood of healthy human donors. Eosinophils were isolated from peritoneal lavages of horse serum-injected guinea pigs. These cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and the production of reactive oxygen species was measured with luminol-dependent chemiluminescence (LDCL).¶Results: M1, an active metabolite of erdosteine, significantly inhibited PMA-induced LDCL of the all cell populations with treatment before stimulation. The effects of S-carboxymethylcysteine (S-CMC), ambroxol and N-acetylcysteine (NAC) on the LDCL response were weaker than those of M1. Furthermore, PMA-induced LDCL was decreased by posttreatment with M1.¶Conclusion: These results suggest that M1 (an active metabolite of erdosteine) may exert an antiinflammatory effect by scavenging inflammatory cells-derived reactive oxygen species.