An in vitro based investigation into the cytotoxic effects of D-amino acids

In the present study, cytotoxic effects of D-Ala, D-Pro and D-Lys are demonstrated. In an effort to study the possible mechanisms of the observed cytotoxicity, catalase activity, H₂O₂ generation, and apoptotic activity were measured in HeLa and MCF-7 cell lines. Although D-Lys is a poor substrate for DAO and therefore low H2O2 was detected, it was shown to provoke severe impairment of cellular integrity and survival. Interestingly, a very good substrate for DAO, such as D-Pro, did not substantially reduce cell viability. On the other hand, a moderate substrate for DAO, represented by D-Ala, was shown to moderately trigger toxicity in the tested cell lines. Although a correlation between the in vitro cytotoxicity of D-amino acids and the amount of H₂O₂ produced was absent, there was a good agreement between the ability of D-amino acids to trigger apoptosis and to provoke toxicity. Our results indicate that the toxicity of D-amino acids does not appear to be solely mediated by H₂O₂. Therefore, we hypothesize that other possible contributing apoptosis-mediated pathways might cause the observed toxicity.