Effects of okadaic acid, azaspiracid-1, yessotoxin and their binary mixtures on human intestinal Caco-2 cells

Authors

  • Jimmy Alarcan German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany https://orcid.org/0000-0002-6509-3012
  • Albert Braeuning German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Straße 8-10, 10589 Berlin, Germany. Tel.: +49-(30)-18412-25100; E-mail: Albert.Braeuning@bfr.bund.de https://orcid.org/0000-0003-3810-027X

DOI:

https://doi.org/10.17179/excli2023-6884

Keywords:

phycotoxins, mixtures, inflammation, Caco-2 cells

Abstract

Phycotoxins are responsible for foodborne intoxications. Symptoms depend on the ingested toxins but mostly imply gastro-intestinal and neurological disorders. Importantly, humans are exposed to combinations of several phycotoxins, resulting in possible mixture effects. Most previous studies, however, have been focused on single toxin effects. Thus, the aim of this study was to examine the effects of binary mixtures of three main phycotoxins, okadaic acid (OA), azaspiracid-1 (AZA1) and yessotoxin (YTX), on human intestinal Caco-2 cells. The focus was placed on cell viability studies and inflammation responses using a multi-parametric approach to assess cell population (nuclei staining), cell metabolism/viability (reductase activity and lysosomal integrity), and release of inflammation markers (e.g., interleukins). Mixture effects were evaluated using the concentration addition (CA) and independent action (IA) models. Our assays show that none of the toxins had an impact on the cell population in the tested concentration range. Only OA modulated reductase activity, while all three toxins had strong effects on lysosomal integrity. Furthermore, all toxins triggered the release of interleukin 8 (IL-8), with OA being most potent. Mixture effect analysis showed additivity in most cases. However, supra-additivity was observed in regards to IL-6 and IL-8 release for combinations implying high concentrations of OA. This study extends the knowledge on mixture effects of phycotoxins in human cells.

Published

2024-04-22

How to Cite

Alarcan, J., & Braeuning, A. (2024). Effects of okadaic acid, azaspiracid-1, yessotoxin and their binary mixtures on human intestinal Caco-2 cells. EXCLI Journal, 23, 509–522. https://doi.org/10.17179/excli2023-6884

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Section

Original articles

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