Analysis of individual and combined toxicity of the dietary biogenic amines tyramine and histamine

Abstract

The biogenic amines (BA) tyramine and histamine are often found at high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity and the increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. For that, we developed an in vitro model of the human intestinal epithelium based on the HT29 cell line and the Real Time Cell Analyzer (RTCA) technology. The RTCA system is used to gather information on cell proliferation, migration and cytotoxicity via changes in cell morphology and adhesion. The dose-response curves, the IC50 (the concentration of BA required to achieve half of the strongest cytotoxic effect observed), the NOAEL (non-observed adverse effect level), and the LOAEL (lowest observed adverse effect level) values, were calculated for tyramine and histamine in proliferating cell cultures. Tyramine and histamine were found to be cytotoxic at concentrations commonly found in BA-rich food. Surprisingly, tyramine -a BA for which legal limit has not been established- had a stronger and more rapid cytotoxic effect than histamine. Their mode of action was also different, while tyramine caused cell necrosis, histamine induced apoptosis. We further found that tyramine and histamine have synergistic cytotoxicity in the range of concentrations that can be found in foods. In fact, histamine at concentrations below the European legal limit increased the cytotoxicity of tyramine at concentrations frequently reached in some foods. In conclusion, to avoid health risks, the accumulation in food of both BA should be reduced, and legal limits that ensure consumer safety should be established for tyramine. Moreover, the synergistic cytotoxicity of tyramine and histamine should be taken into account when establishing legal limits.