Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine

Tyramine and histamine, the most toxic biogenic amines (BA), are often found in high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity, and increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. Tyramine and histamine were toxic for HT29 intestinal cell cultures at concentrations commonly found in BA-rich food, as determined by real-time cell analysis. Surprisingly, tyramine 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. To avoid health risks, the BA content of foods should be reduced and legal limits established for tyramine.This work was funded by the Spanish Ministry of Economy and Competitiveness (AGL2013-45431-R) and by the GRUPIN14-137 project, which is co-financed by the Plan for Science, Technology and Innovation of the Principality of Asturias 2014-2017 and the European Regional Development Funds.Peer reviewe

Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine

Tyramine and histamine, the most toxic biogenic amines (BA), are often found in high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity, and increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. Tyramine and histamine were toxic for HT29 intestinal cell cultures at concentrations commonly found in BA-rich food, as determined by real-time cell analysis. Surprisingly, tyramine 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. To avoid health risks, the BA content of foods should be reduced and legal limits established for tyramine.This work was funded by the Spanish Ministry of Economy and Competitiveness (AGL2013-45431-R) and by the GRUPIN14-137 project, which is co-financed by the Plan for Science, Technology and Innovation of the Principality of Asturias 2014-2017 and the European Regional Development Funds.Peer reviewe

Multi-instrumental observations of the 2014 Ursid meteor outburst

The Ursid meteor shower is an annual shower that usually shows little activity. However, its Zenith hourly rate sometimes increases, usually either when its parent comet, 8P/Tuttle, is close to its perihelion or its aphelion. Outbursts when the comet is away from perihelion are not common and outbursts when the comet is close to aphelion are extremely rare. The most likely explanation offered to date is based on the orbital mean motion resonances. The study of the aphelion outburst of 2000 December provided a means of testing that hypothesis. A new aphelion outburst was predicted for 2014 December. The SPanish Meteor Network, in collaboration with the French Fireball Recovery and InterPlanetary Observation Network, set up a campaign to monitor this outburst and eventually retrieve orbital data that expand and confirm previous preliminary results and predictions. Despite unfavourable weather conditions over the south of Europe over the relevant time period, precise trajectories from multistation meteor data recorded over Spain were obtained, as well as orbital and radiant information for four Ursid meteors. The membership of these four meteors to the expected dust trails that were to provoke the outburst is discussed, and we characterize the origin of the outburst in the dust trail produced by the comet in the year AD 1392.Peer reviewe

Orbits and emission spectra from the 2014 Camelopardalids

We have analyzed the meteor activity associated with meteoroids of fresh dust trails of Comet 209P/LINEAR, which produced an outburst of the Camelopardalid meteor shower (IAU code #451, CAM) in May 2014. With this aim, we have employed an array of high-sensitivity CCD video devices and spectrographs deployed at 10 meteor observing stations in Spain in the framework of the Spanish Meteor Network (SPMN). Additional meteoroid flux data were obtained by means of two forward-scatter radio systems. The observed peak zenithal hourly rate (ZHR) was much lower than expected, of around 20 meteors h-1. Despite of the small meteor flux in the optical range, we have obtained precise atmospheric trajectory, radiant and orbital information for 11 meteor and fireball events associated with this stream. The ablation behaviour and low tensile strength calculated for these particles reveal that Camelopardalid meteoroids are very fragile, mostly pristine aggregates with strength similar to that of the Orionids and the Leonids. The mineral grains seem to be glued together by a volatile phase. We also present and discuss two unique emission spectra produced by two Camelopardalid bright meteors. These suggest a non-chondritic nature for these particles, which exhibit Fe depletion in their composition.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society on Sept. 22, 201

Evidence of the cytotoxic and synergistic effects of the biogenic amines tyramine and histamine, which can accumulate at high concentrations in cheese because of the decarboxylative metabolism of some LAB

Trabajo presentado en el 12th International Symposium on Lactic Acid Bacteria, celebrado en Egmond aan Zee (Holanda) del 27 al 31 de agosto de 2017Lactic acid bacteria (LAB) play an essential role in the production of a large diversity of fermented foods. The long and harmless history of use of LAB in food fermentations has resulted in them being generally recognized as safe. However, some LAB possess enzymatic activities that produce undesirable toxic compounds, such as the biogenic amines (BA) tyramine and histamine. In cheese, one of the foods in which the highest concentrations of BA can be found, they are produced predominantly by LAB. More specifically, Enterococcus faecalis is the main responsible for the accumulation of tyramine, while Lactobacillus parabuchneri is the species mainly responsible for the accumulation of histamine. Although the European Food Safety Authority (EFSA) deems tyramine and histamine to be the most toxic BA, it also concludes that our present knowledge of their toxicity is limited, and that further research is needed. In this communication, we present an analysis of the in vitro cytotoxicity of tyramine and histamine, individually and in combination, towards intestinal cells in culture. To perform these analyses, we have developed an in vitro model of the human intestinal epithelium based on the HT29 cell line and the Real Time Cell Analyzer (RTCA) technology. Tyramine and histamine were found to be cytotoxic at concentrations commonly found in some types of cheese. Surprisingly, tyramine -a BA for which no legal limit has 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.Peer reviewe

Toxicidad in vitro de las aminas biógenas tiramina e histamina

Trabajo presentado en la 10ª Reunión de la Red Española de Bacterias Lácticas, celebrada en Madrid el 23 y 24 de Junio de 2016[Introducción] La tiramina y la histamina son las aminas biógenas (AB) que más frecuentemente y a más altas concentraciones se encuentran en el queso, debido al catabolismo de los aminoácidos de determinadas BAL. El consumo de alimentos con una alta concentración de tiramina o histamina causa diversas reacciones tóxicas que pueden ser más o menos graves dependiendo de la susceptibilidad del consumidor. La autoridad europea de seguridad alimentaria (EFSA) considera que la tiramina y la histamina son las AB más tóxicas. Sin embargo, a pesar de las altas concentraciones que ambas pueden alcanzar en queso, solo está regulado el contenido de histamina en pescado y sus derivados. El panel de riesgos biológicos de la EFSA recomendó en 2011 avanzar en el estudio de los efectos tóxicos de las AB, con el fin de establecer sus límites legales. [Objetivos] Determinar la citotoxicidad in vitro de la tiramina y la histamina, así como su modo de acción. [Materiales y Métodos] La toxicidad de estas AB se evaluó en un modelo in vitro de epitelio intestinal humano (células HT29), empleando la tecnología RTCA (Real Time Cell Analysis) para monitorizar cambios celulares en tiempo real debidos al tratamiento con AB. El análisis se realizó en células en proliferación tratadas con concentraciones crecientes de tiramina o histamina. Se determinaron las curvas dosis-respuesta, la concentración que causa la mitad del efecto tóxico máximo observado (IC50), la concentración más alta que no tiene efecto tóxico (NOAEL) y la concentración más baja que tiene efecto tóxico (LOAEL). El modo de acción de estas AB -necrosis o apoptosis- se determinó mediante el ensayo de la lactato deshidrogenasa (LDH) y la cuantificación de la fragmentación del DNA celular, respectivamente. [Resultados]: Ambas AB resultaron tóxicas para las células HT29, siendo la tiramina más citotóxica (IC50: 3.2±0.04 mM, NOAEL: 1.8 mM y LOAEL: 2.2 mM ) que la histamina (IC50: 26.0±1.20 mM, NOAEL: 3 mM y LOAEL: 4 mM). La tiramina provocó un aumento de la actividad LDH en el sobrenadante celular, mientras que la histamina causó la fragmentación del DNA. El tratamiento simultáneo con ambas AB demostró un efecto citotóxico mayor al correspondiente a la suma de sus efectos tóxicos individuales. [Conclusiones] La tiramina y la histamina son citotóxicas y tienen efecto sinérgico a las concentraciones que se pueden encontrar en alimentos ricos en AB. La tiramina es más tóxica y causa necrosis celular, mientras que la histamina induce apoptosis. Además de los límites legales establecidos para la histamina en pescado, sería recomendable el establecimiento de límites máximos también para la tiramina y en otros alimentos de riesgo.Este trabajo ha sido financiado por el Ministerio de Economía y Competitividad (AGL2012-33278 y AGL2013-45431-R) y por el proyecto GRUPIN14-137 (cofinanciado por el Principado de Asturias y por los fondos FEDER)Peer reviewe

Analisis con individual and combined toxicity of the dietary biogenic amines tyramine and histamine

Trabajo presentado en The 1st Food Chemistry Conference, celebrada en Amsterdam (Holanda) del 30 de octubre al 1 de noviembre de 2016Peer reviewe

The dietary biogenic amines tyramine and histamine show synergistic toxicity towards intestinal cells in culture

Tyramine and histamine are the biogenic amines (BA) most commonly found at high concentrations in food; they may even appear together at toxic concentrations. The present work examines, via real-time cell analysis, whether histamine and tyramine show synergistic toxicity towards intestinal cell cultures. Employing a constant equipotency ratio, their interaction was examined via the combination index (CI) method of Chou & Talalay. Co-treatment with tyramine and histamine was associated with a stronger cytotoxic effect than was treatment with either BA or on its own. Indeed, a synergistic interaction (CI < 1) was observed in the range of concentrations found in foods. The results also show that histamine, at concentrations below the legal limit, increases the cytotoxicity of tyramine at concentrations frequently reached in some foods. The synergistic cytotoxicity of tyramine and histamine should be taken into account when establishing legal limits designed to ensure consumer safety.This work was funded by the Spanish Ministry of Economy and Competitiveness (AGL2013-45431-R & AGL2015-64901-R) and by the GRUPIN14-137 project (which is co-financed by the Plan for Science, Technology and Innovation of the Principality of Asturias 2013–2017 and European Regional Development Funds).Peer reviewe

The biogenic amines putrescine and cadaverine show in vitro cytotoxicity at concentrations that can be found in foods

Putrescine and cadaverine are among the most common biogenic amines (BA) in foods, but it is advisable that their accumulation be avoided. Present knowledge about their toxicity is, however, limited; further research is needed if qualitative and quantitative risk assessments for foods are to be conducted. The present work describes a real-time analysis of the cytotoxicity of putrescine and cadaverine on intestinal cell cultures. Both BA were cytotoxic at concentrations found in BA-rich foods, although the cytotoxicity threshold for cadaverine was twice that of putrescine. Their mode of cytotoxic action was similar, with both BA causing cell necrosis; they did not induce apoptosis. The present results may help in establishing legal limits for both putrescine and cadaverine in foodThis work was funded by the Spanish Ministry of Economy and Competitiveness (AGL2016-78708-R and AGL2015-64901-R)Peer reviewe