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Permeability and toxicity characteristics of L-cysteine and 2-methyl-thiazolidine-4-carboxylic acid in Caco-2 cells.
MedLine Citation:
PMID:  22356486     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Alma Kartal-Hodzic; Tuuli Marvola; Mechthild Schmitt; Kirsi Harju; Marikki Peltoniemi; Mia Sivén
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-22
Journal Detail:
Title:  Pharmaceutical development and technology     Volume:  -     ISSN:  1097-9867     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9610932     Medline TA:  Pharm Dev Technol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Faculty of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki , Helsinki , Finland.
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