Scavenging of reactive oxygen species by letosteine, a molecule with two blocked-SH groups. Comparison with free-SH drugs.
Acute production of reactive oxygen species by polymorphonuclear neutrophils during the respiratory burst may induce tissue injuries. In this in vitro study, it was demonstrated that letosteine, a mucolytic agent containing two blocked thiol groups, had antioxidant activity, but only when it was first submitted to alkaline hydrolysis. In a cell-free system, hydrogen peroxide, hypochlorous acid and hydroxyl radical concentrations were reduced by half by letosteine concentrations of 200, 15 and 350 mumol/l, respectively. The mechanism of letosteine action may be related to the -SH group liberated in vitro by hydrolysis, which seemed to react by scavenging the reactive oxygen species in the same way as acetylcysteine and MESNA, free-thiol drugs known for their antioxidant properties. So, letosteine, a compound with blocked -SH groups which in vivo can metabolically become free, may have a therapeutic application in preventing oxidative tissue injury damage induced by the respiratory burst.
Gressier
B
B
Faculté de Pharmacie, Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Lille, France.
Lebegue
N
N
Brunet
C
C
Luyckx
M
M
Dine
T
T
Cazin
M
M
Cazin
J C
JC
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000009:adverse effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005100:Expectorants / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D017665:Hydroxyl Radical / Q000009:adverse effects / Q000378:metabolism; D006997:Hypochlorous Acid / Q000009:adverse effects / Q000378:metabolism; D015080:Mesna / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000009:adverse effects / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D053778:Thiazolidines
D000975:Antioxidants; D005100:Expectorants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D013844:Thiazoles; D053778:Thiazolidines; D013481:Superoxides; D017665:Hydroxyl Radical; C018578:letosteine; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D015080:Mesna; D000111:Acetylcysteine