Azaspiracid: An Emerging Algal Toxin
Project Status: This project began in January, 2003 and is Ongoing
Azaspiracids are a group of toxins first reported in the 1990s in Western European waters and are now reported to occur along both the East and West coasts of North America. While the organism producing these toxins has been identified, the mechanism by which azaspiracids exert their toxic effects remains to be determined. We are conducting studies to better understand the toxicology of azaspiracids, an emerging class of algal toxins in United States coastal waters.
Why We Care
Azaspiracids are a group of algal toxins responsible for the human illness known as azaspiracid shellfish poisoning (AZP), first encountered in Western Europe in the mid-1990s. Since then, multiple AZP outbreaks involving human illness have been reported in several European countries. The toxin has been detected in shellfish from North Africa and eastern Canada, and most recently in the Pacific Northwest area of the United States. With clear evidence that azaspiracids are present in shellfish from United States waters, including oysters, mussels, and razor clams, establishing the mechanism of toxicity for these compounds is critical and essential to understanding the human health risks presented by these emerging toxins.
What We’re Doing
In collaboration with our partners, we began by obtaining sufficient purified azaspiracids to conduct toxicology tests in the laboratory. We are working with scientists from the University of Michigan at Dearborn, the National Research Council of Canada, the Irish Marine Institute, and others in the European Union.
What We’re Finding
Toxic effects of azaspiracids on human cells:
toxic to many different cell lines;
cause morphological changes to cells;
alter gene expression patterns in cells;
cause decline in cell cholesterol levels.
Toxic effects of azaspiracids on fish:
disrupt the development of embryos.
In addition, there appear to be clear differences in the toxicity of different azaspiracids and possibly the way they exert their toxic effects, all of which will be need to be taken into account when monitoring these toxins in shellfish and assessing the risk they pose to consumers.
We continue to perform laboratory studies to try and identify the precise mode of action for the azaspiracids. In addition, we are working with our partners to perform studies using mammalian model systems to better understand and ultimately predict how these toxins may be metabolized or processed following ingestion of contaminated shellfish by humans.
Related Regions of Study: Canada, Ireland, Michigan, South Carolina, Washington
Primary Contact: Greg Doucette
Harmful Algal Blooms
Related NCCOS Center: CCEHBR
- Colman, Jamie R., Michael J. Twiner, Philipp Hess, Terry McMahon, Masayuki Satake, Takeshi Yasumoto, Gregory J. Doucette, and John S. Ramsdell. 2005. Teratogenic effects of azaspiracid-1 identified by microinjection of Japanese medaka (Oryzias latipes) embryos. Toxicon 45(7):881-890
- Twiner, Michael J., Philipp Hess, Marie-Yasmine Bottein Dechraoui, Terry McMahon, Melissa S. Samons, Masayuki Satake, Takeshi Yasumoto, John S. Ramsdell, and Gregory J. Doucette. 2005. Cytotoxic and cytoskeletal effects of azaspiracid-1 on mammalian cell lines. Toxicon 45(7):891-900.
- Kulagina, Nadezhda V., Michael J. Twiner, Philipp Hess, Terry McMahon, Masayuki Satake, Takeshi Yasumoto, John S. Ramsdell, Gregory J. Doucette, Wu Ma, and Thomas J. O'Shaughnessy. 2006. Azaspiracid-1 inhibits bioelectrical activity of spinal cord neuronal networks. Toxicon 47(7):766-773.
- Twiner, Michael J. , James C. Ryan, Jeanine S. Morey, Kent J. Smith, Samar M. Hammad, Frances M. Van Dolah, Philipp Hess, Terry McMahon, Masayuki Satake, Takeshi Yasumoto, and Gregory J. Doucette. 2008. Transcriptional profiling and inhibition of cholesterol biosynthesis in human lymphocyte T cells by the marine toxin azaspiracid. Genomics 91(3):289-300.
- Twiner, Michael J., Nils Rehmann, Philipp Hess, and Gregory J. Doucette. 2008. Azaspiracid Shellfish Poisoning: A review on the chemistry, ecology, and toxicology with an emphasis on human health impacts. Marine Drugs 6(2):39-72.
- Twiner, Michael J., Racha El-Ladki, Jane Kilcoyne, and Gregory J. Doucette. 2012. Comparative effects of the marine algal toxins azaspiracid-1, -2, and -3 on Jurkat T lymphocyte cells. Chemical Research in Toxicology 25(3):747-754.
- Twiner, Michael J., Joshua C. Hanagriff, Suzanne Butler, Ahmed K. Madhkoor, and Gregory J. Doucette. 2012. Induction of apoptosis pathways in several cell lines following exposure to the marine algal toxin azaspiracid. Chemical Research in Toxicology 25(7):1493-1501
- Twiner, Michael J., Gregory J. Doucette, Andrew Rasky, Xi-Ping Huang, Bryan L. Roth, and Michael C. Sanguinetti. 2012. Marine algal toxin azaspiracid is an open-state blocker of hERG potassium channels. Chemical Research in Toxicology 25(9):1975-1984.