Free Radical Scavenging Activity of Erdosteine Metabolite I Investigated by Electron Paramagnetic Resonance Spectroscopy

Abstract

The aim of this study was to explore the antiradical activity of Met I (an active metabolite of erdosteine) containing a pharmacologically active sulphydryl group, by means of electron paramagnetic resonance (EPR) spectroscopy which has not previously been used to characterize the antiradical activity of Met I. The effects of concentrations of 20, 10, 5, 2.5, 1.25 and 0.625 µg/ml of Met I were tested against: (a) the Fenton reaction model system with EPR detection of HO^·; (b) the KO₂-crown ether system with EPR detection of O₂^{^–}^·; (c) the EPR assay based on the reduction of the Tempol radical, and (d) the EPR assay based on the reduction of Fremy’s salt radical. Our findings show that the intensity of 4 different free radicals was significantly reduced in the presence of Met I, thus indicating the presence of a termination reaction between the free radicals and Met I.

Protective effect of erdosteine metabolite I against hydrogen peroxide-induced oxidative DNA-damage in lung epithelial cells

“…Given the particularposition of sulphur in the periodic scale,the thiol group( SH)i sagood electron donor, and soR-SH arem oree asilyoxidised orconjugated thancompoundsbearing -OH or-NH 2 moieties [26]. ThisSH anti-oxidantmechanismh asalsobeen confirmed byfindingsabout the activity of sulphurous thermalwater,anaturalsourceo fSH residuest hataren ot carried byothermolecularmoieties [27].Recently,it hasbeen shownthat in vitro MetIinhibits oxidative stress mediators (ROS, RNS, peroxynitrite) during the respiratory burst of humanneutrophils [17,18], and also inhibits elastaserelease [19].MET Ibecomespharmacologicallyavailable aftererdosteine hepaticmetabolisation,a nd hasfree radicalscavenging and anti-inflammatory activities [12,20], whichcould bewidely exploited in COPD [28,29]and otherlung diseasessuch aspulmonary fibrosisin whicho xidativestress plays an importantpathogeneticrole [30,31].Recentclinicalstudiesevidenceh aveshownthatithasaprotectivee ffect on nicotine-induced tissueinjury,and soerdosteine administration mayprevents moking-induced lipid peroxidation [32].…”

“…n A549 cells n Anti-oxidantactivity n DNA damage n Erdosteine metaboliteI n Genotoxicity Arzneimittelforschung 2011;61(12):700-706 closed in the heterocyclicring (thiolactone). The molecule isapro-drugbecause,a lthough itdoesnothavea free SH groupi tself,itproducesanactivem etabolite (MET I)containing apharmacologicallyactiveSH group afterfirst-pass metabolism [15].Erdosteine wasoriginallydeveloped asamucomodulatory (mucolytic)agent fort he treatmentof respiratory diseases [16], but ithas morerecentlybeen shownthatt he activeMET Ihas anti-oxidantactivity [17][18][19][20].Oxidativestress isamajor mechanismforcell damage followed byavariety of secondary cellularprocesses.DNA isone of the most sensitivebiomoleculestothe action of ROS and free radicals, whichm ayr upturesingle ordouble strands,a nd this damagest he basesorbreakh ydrogen bonds.The aim of thiss tudyw ast oi nvestigatethe protectivee ffectof MET Iagainst H 2 O 2 -induced oxidativestress and oxidatived amage DNA using ac ometassayof A549 human lung epithelialcells.…”

Multifaceted Beneficial Effects of Erdosteine: More than a Mucolytic Agent

“…Met 1 was also effective in preventing H 2 O 2 -induced oxidative stress and DNA damage in A549 human lung adenocarcinoma cells by the scavenging of intracellular ROS [ 9 ]. It has been documented that the –SH group of Met 1 is capable of reducing the amount of N-centred radical species because of a termination reaction between the free radicals and Met 1 as a mechanism to explain the antioxidant effect of this drug [ 10 ]. Erdosteine has also been demonstrated to prevent or reduce lung tissue damage induced by oxidative stress in a variety of experimental models [ 11 – 13 ].…”

Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf‐2/HO‐1 pathway

“…Erdosteine [N‐(carboxymethylthioacetyl)‐homocysteinethiolactone] was instigated more than 20 years back for the treatment of pulmonary disorders, as it has mucolytic and mucomodulatory properties. [ 11 ] It contains two blocked sulfhydryl moieties, one of which gets metabolized after first‐pass metabolism and helps to rummage free oxygen radicals. [ 12,13 ] Erdosteine is stable in dry state at acidic pH of stomach, whereas its thiolactone ring opens up and convert to an active metabolite, that is, N‐thiodiglycolylhomocysteine in alkaline condition.…”