As human co-exposure to natural toxins through food and water is inevitable, risk assessments to safeguard health are necessary. Aflatoxin B1 and fumonisin B1, frequent co-contaminants of maize and microcystin-LR, produced in freshwater by cyanobacteria are all naturally occurring potent toxins that threaten human health. Populations in the poorest regions of the world may suffer repeated simultaneous exposure to these contaminants. Using High Content Analysis, multiple cytotoxicity endpoints were measured for the individual toxins and mixtures in various cell lines. Results highlighted that significant cytotoxic effects were observed for aflatoxin B1 in all cell lines while no cytotoxic effects were observed for fumonisin B1 or microcystin-LR. Aflatoxin B1/microcystin-LR was cytotoxic in the order HepG2 > Caco-2 > MDBK. Fumonisin B1/microcystin-LR affected MDBK cells. The ternary mixture was cytotoxic to all cell lines. Most combinations were additive, however antagonism was observed for binary and ternary mixtures in HepG2 and MDBK cell lines at low and high concentrations. Synergy was observed in all cell lines, including at low concentrations. The combination of these natural toxins may pose a significant risk to populations in less developed countries. Furthermore, the study highlights the complexity around trying to regulate for human exposure to multiple contaminants.

• Klíčová slova
• Aflatoxin B(1), Combined exposure, Cytotoxicity, Fumonisin B(1), High content analysis, Microcystin-LR,
• MeSH
• aflatoxin B1 aplikace a dávkování   chemie   toxicita   MeSH
• biologické markery moč   MeSH
• biologické toxiny MeSH
• buněčné linie MeSH
• fumonisiny aplikace a dávkování   chemie   toxicita   MeSH
• kontaminace potravin MeSH
• lidé MeSH
• mikrocystiny aplikace a dávkování   chemie   toxicita   MeSH
• mořské toxiny MeSH
• skot MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aflatoxin B1 MeSH
• biologické markery MeSH
• biologické toxiny MeSH
• cyanoginosin LR MeSH Prohlížeč
• fumonisin B1 MeSH Prohlížeč
• fumonisiny MeSH
• mikrocystiny MeSH
• mořské toxiny MeSH

Toxic cyanobacteria represent a serious health and ecological problem in drinking and recreational waters worldwide. Some previous toxicological studies investigated effects of isolated microcystins on laboratory rodents including mice and rats. However, much less attention has been paid to more realistic exposure situations such as the effects of MCs accumulated in food. The objectives of the present study were to provide a simple model simulation of the food chain in order to evaluate impacts of microcystins (MCs) on rat immune and haematologicalparameters. Impacts of feeding experimental rats with a diet containing fish meat with and without microcystins and complex toxic biomass have been studied during a 28 day exposure. Red blood cell parameters (RBC counts, haematocrit values, MCH, MCV and MCHC) showed significant differences in experimental groups (p ≤ 0.05, p ≤ 0.01) in comparison with the control group. We also detected an immunomodulatory effect in the experimental groups. NK cells and γδ+ T lymphocytes were significantly increased in peripheral blood in the group exposed to isolated microcystin in the food. Significant change in the ratio of CD4+ and CD8+ cells (increase of CD4+ and a drop in CD8+) was found in the group with added cyanobacterial biomass with low concentration of MCs. The greatest changes in lymphoid organs were observed in the same groups. There was an increase of spleen subpopulations of γδ+ T lymphocytes as well as of IgM+ lymphocytes (B lymphocytes) and CD8+ T lymphocytes. Indeed, the modulation of CD4+ and CD8+ of peripheral lymphocytes was associated with similar changes in thymic lymphocytic subpopulations. In summary, food containing fish meat with considerable doses of microcystins (or toxic cyanobacterial biomass) induces significant changes in RBC parameters and influence preferably innate part of the immune system represented by NK cells and by gamma-delta T cells, which are known to play role as a bridge between adaptive and innate immune response.

• Klíčová slova
• Cyanobacteria, Immunomodulation, Lymphocyte subpopulations, Red blood cells, Wistar albino rats,
• MeSH
• analýza rozptylu MeSH
• buňky NK imunologie   MeSH
• hematokrit MeSH
• kontaminace potravin MeSH
• krysa rodu Rattus MeSH
• mikrocystiny aplikace a dávkování   toxicita   MeSH
• počet erytrocytů MeSH
• poměr CD4 a CD8 lymfocytů MeSH
• potkani Wistar MeSH
• přirozená imunita účinky léků   MeSH
• reologie krve účinky léků   MeSH
• sinice chemie   MeSH
• slezina cytologie   účinky léků   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikrocystiny MeSH