Scavenging of reactive oxygen species by letosteine, a molecule with two blocked-SH groups. Comparison with free-SH drugs.

Abstract

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.