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.


CONCLUSIONS
These results suggest that M (an active metabolite of erdosteine) may exert an antiinflammatory effect by scavenging inflammatory cells-derived reactive oxygen species.
Miyake
K
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Sizuoka, Japan.
Kaise
T
T
Hosoe
H
H
Akuta
K
K
Manabe
H
H
Ohmori
K
K
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D005100:Expectorants / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010533:Peritoneal Lavage; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013864:Thioglycolates / Q000378:metabolism / Q000494:pharmacology*; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D005100:Expectorants; D017382:Reactive Oxygen Species; D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D013755:Tetradecanoylphorbol Acetate