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.

Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis

“…Peak MTCA concentrations of gastric juice were over 20-fold lower than MTCA levels found to be non-toxic to Caco-2 cell lines in vitro. [33] MTCA is an endogenous product that is detected in the blood after a moderate ethanol dose (0.5 g/kg). [34] Furthermore, it has been shown that MTCA can serve as a prodrug for L-cysteine and thus protect mice against acetaminophen toxicity.…”

Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism

“…1). 9,10,27 Treatment of HEK293T cells with HCHO or AcH led to increased thioproline and MTCA levels, respectively (Fig. 1b).…”

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“…In cytotoxicity assays, Kartal-Hodzic et al showed that L-cysteine was not toxic to the Caco-2 cells until a concentration of 9.9 mM was reached. The results of this toxicity study are very interesting because it demonstrated that L-cysteine might be able to be used in different formulations [22]. Previously, was reported that L-cysteine and L-cystine greatly potentiated the bactericidal effect of hydrogen peroxide in E. coli K-12 [23].…”