Synthese, Analytik und toxikologische Charakterisierung von Arsenolipiden
Zusammenfassung der Projektergebnisse
Although fish and seafood are well known for their nutritional benefits, they contain contaminants that might affect human health. Organic lipid-soluble arsenic species, so called arsenolipids, belong to the emerging, not yet toxicologically characterized, contaminants in these food items. In this DFG/FWF joint project we characterized the toxicity of four food-relevant arsenolipid classes (arsenic containing hydrocarbons, arsenic containing fatty acids, arsenic containing triacylglycerides and arsenic containing phosphatidylcholines) applying the model organisms cell cultures, the nematode Caenorhabditis elegans and mice. After our Austrian colleagues had successfully synthesized these arsenolipids we could demonstrate that in principle, all synthesized arsenolipids were biologically available to the test organisms. The arsenic containing triacylglycerides and phosphatidylcholines exerted low toxicity comparable to that shown by arsenic containing fatty acids and considerably less than that of the arsenic containing hydrocarbons. Moreover, these more complex arsenolipids were not always chemically stable in the respective media. With respect to the arsenic containing hydrocarbons our in vitro and in vivo studies have clearly identified the potential toxic nature of these arsenolipids, and raised issues for health and food regulatory authorities, and for epidemiologists studying human populations exposed to arsenic. Of particular concern is the potential neurotoxic effect of the arsenic containing hydrocarbons on the infant brain during crucial early developmental stages. Overall, this joint project clearly indicates that we deserve both further food occurrence data for a reliable exposure assessment and toxicity data for a hazard characterization to assess whether arsenolipids and especially arsenic-containing hydrocarbons pose a risk to human health.
Projektbezogene Publikationen (Auswahl)
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(2017). Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons. Molecular nutrition & food research, 61(11), 1700199
Witt B, Ebert F, Meyer S, Francesconi KA & Schwerdtle T
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(2017). Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons. Archives of Toxicology, 91(9), 3121-3134
Witt B, Meyer S, Ebert F, Francesconi KA & Schwerdtle T
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(2018). Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells. Archives of Toxicology, 92(5), 1751-1765
Müller SM, Finke H, Ebert F, Kopp JF, Schumacher F, Kleuser B, Francesconi KA, Raber G & Schwerdtle T
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(2018). Effects of arsenolipids on in vitro blood-brain barrier model. Archives of toxicology, 92(2), 823-832
Müller SM, Ebert F, Raber G, Meyer S, Bornhorst J, Hüwel S, Galla HJ, Francesconi KA & Schwerdtle T
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(2020). Toxicity of three types of arsenolipids: species-specific effects in Caenorhabditis elegans. Metallomics, 12(5), 794-798
Bornhorst J, Ebert F, Meyer S, Ziemann V, Xiong C, Guttenberger N, Raab A, Baesler J, Aschner M, Feldmann J, Raber G, Francesconi KA & Schwerdtle T
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(2020). Toxicological assessment of arsenic containing phosphatidylcholines in HepG2 cells. Metallomics, 12, 1159-1170
Finke H, Wandt VK, Ebert F, Guttenberg N, Glabonjat RA, Stiboller M, Francesconi KA, Raber G & Schwerdtle T