title: Increasing sputum levels of gamma-glutamyltransferase may identify cystic fibrosis patients who do not benefit from inhaled glutathione.
abstract: Glutathione (GSH) is decreased in cystic fibrosis (CF) airways, thus its resupply by inhalation has been employed to restore antioxidant defense. CF airways present however increased activity of gamma-glutamyltransferase (GGT), the enzyme specifically capable of degrading GSH, and thus inhaled GSH might be promptly catabolized. In addition, prooxidant reactions are known to originate during GGT-mediated GSH catabolism. We determined levels of GGT in the sputum samples obtained from a previously published trial of GSH inhalation treatment, and analyzed their correlations with inflammatory markers and FEV1% values. Results indicate that differentiating patients with increasing vs. decreasing GGT activity - as measured in sputum before and after the six months duration of the study - may discriminate subjects more likely profiting from inhaled GSH, as opposed to those with increasing GGT in which these treatments might even produce aggravation of the damage.
authors.affiliation: Dept. of Translational Research NTMC, University of Pisa, Italy. Electronic address: alessandro.corti@med.unipi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corti
authors.affiliation: Children's Hospital, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.affiliation: University of Tübingen Children's Hospital, Section of Pediatric Infectiology and Immunology, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hector
authors.affiliation: Dept. of Translational Research NTMC, University of Pisa, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pompella
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005978:Glutathione / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D011379:Prognosis; D013183:Sputum / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000032:analysis / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005723:gamma-Glutamyltransferase; D005978:Glutathione
keywords: Cystic fibrosis; Gamma-glutamyltransferase; Glutathione; Inflammation