title: Permeability and toxicity characteristics of L-cysteine and 2-methyl-thiazolidine-4-carboxylic acid in Caco-2 cells.
abstract: Acetaldehyde is a known mutagenic substance and has been classified as a group-one carcinogen by the WHO. It is possible to bind acetaldehyde locally in the gastrointestinal (GI) tract with the semi-essential amino acid l-cysteine, which reacts covalently with acetaldehyde and forms compound 2-methyl-thiozolidine-4-carboxylic acid (MTCA). The Caco-2 cell line was used to determine the permeation of l-cysteine and MTCA, as well as the possible cell toxicity of both substances. Neither of the substances permeated through the Caco-2 cells at the concentrations used in this study, and only the highest concentration of MTCA affected the viability of the cells in the MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) test. These results showed that when l-cysteine is administered in formulations releasing it locally in the lower parts of GI tract, it is not absorbed but can react with acetaldehyde, and that neither l-cysteine nor MTCA is harmful to the cells when present locally in the upper parts of GI tract. This study also shows that MTCA is sensitive at a lower pH of 5.5. Since stable MTCA is desired in different parts of the GI tract, this observation raises concern over the influence of lower pH on l-cysteine-containing product ability to bind and eliminate carcinogenic acetaldehyde.
authors.affiliation: Faculty of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki, Helsinki, Finland. alma.kartal@helsinki.fi
authors.forename: Alma
authors.initials: A
authors.lastname: Kartal-Hodzic
authors.forename: Tuuli
authors.initials: T
authors.lastname: Marvola
authors.forename: Mechthild
authors.initials: M
authors.lastname: Schmitt
authors.forename: Kirsi
authors.initials: K
authors.lastname: Harju
authors.forename: Marikki
authors.initials: M
authors.lastname: Peltoniemi
authors.forename: Mia
authors.initials: M
authors.lastname: Sivén
mesh_terms: D000079:Acetaldehyde / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003545:Cysteine / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010539:Permeability; D053778:Thiazolidines / Q000493:pharmacokinetics* / Q000633:toxicity*
chemical_list: D053778:Thiazolidines; C003438:thiazolidine-4-carboxylic acid; D000079:Acetaldehyde; D003545:Cysteine