SCAVENGING OF REACTIVE OXYGEN SPECIES BY LETOSTEINE, A MOLECULE WITH 2 BLOCKED -SH GROUPS - COMPARISON WITH FREE -SH DRUGS

Acute production of reactive oxygen species by polymorphonuclear neutr ophils during the respiratory burst may induce tissue injuries. In thi s in vitro study, it was demonstrated that letosteine, a mucolytic age nt containing two blocked thiol groups, had antioxidant activity, but only when it was first submitted to alkaline hydrolysis. In a cell-fre e system, hydrogen peroxide, hypochlorous acid and hydroxyl radical co ncentrations were reduced by half by letosteine concentrations of 200, 15 and 350 mu mol/l, respectively. The mechanism of letosteine action may be related to the -SH group liberated in vitro by hydrolysis, whi ch seemed to react by scavenging the reactive oxygen species in the sa me way as acetylcysteine and MESNA, free-thiol drugs known for their a ntioxidant properties. So, letosteine, a compound with blocked -SH gro ups which in vivo can metabolically become free, may have a therapeuti c application in preventing oxidative tissue injury damage induced by the respiratory burst.