S-CMC-Lys protective effects on human respiratory cells during oxidative stress.
The mucoactive drug S-carbocysteine lysine salt monohydrate (S-CMC-Lys) stimulates glutathione (GSH) efflux from respiratory cells. Since GSH is one of the most important redox regulatory mechanisms, the aim of this study was to evaluate the S-CMC-Lys effects on GSH efflux and intracellular concentration during an oxidative stress induced by the hydroxyl radical (xOH). Experiments were performed on cultured human respiratory WI-26VA4 cells by means of patch-clamp experiments in whole-cell configuration and of fluorimetric analyses at confocal microscope. xOH exposure induced an irreversible inhibition of the GSH and chloride currents that was prevented if the cells were incubated with S-CMC-Lys. In this instance, the currents were inhibited by the specific blocker CFTR(inh)-172. CFT1-C2 cells, which lack a functional CFTR channel, were not responsive to S-CMC-Lys, but the stimulatory effect of the drug was restored in LCFSN-infected CFT1 cells, functionally corrected to express CFTR. Fluorimetric measurements performed on the S-CMC-Lys-incubated cells revealed a significant increase of the GSH concentration that was completely hindered after oxidative stress and abolished by CFTR(inh)-172. The cellular content of reactive oxygen species was significantly lower in the S-CMC-Lys-treated cells either before or after xOH exposure. As a conclusion, S-CMC-Lys could exert a protective function during oxidative stress, therefore preventing or reducing the ROS-mediated inflammatory response.
Garavaglia
Maria Lisa
ML
Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Milan, Italy.
Bononi
Elena
E
Dossena
Silvia
S
Mondini
Anna
A
Bazzini
Claudia
C
Lanata
Luigi
L
Balsamo
Rossella
R
Bagnasco
Michela
M
Conese
Massimo
M
Bottà
Guido
G
Paulmichl
Markus
M
Meyer
Giuliano
G
D002233:Carbocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D005470:Fluorometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D012137:Respiratory System / Q000166:cytology*
D020011:Protective Agents; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C034932:carbocysteine-lysine; D017665:Hydroxyl Radical; D002233:Carbocysteine; D005978:Glutathione