Characterization of biologically inactive spirolides E and F: Identification of the spirolide pharmacophore

Hu, Tingmo; Curtis, Jonathan M.; Walter, John A.; Wright, Jeffrey L. C.

doi:10.1016/0040-4039(96)01721-2

Cited by 136 publications

(133 citation statements)

References 5 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…A group of novel marine toxins, macrocyclic imines known as spirolides, was isolated and characterized from shellfish (Hu et al, 1995(Hu et al, , 1996 and later from plankton (Cembella et al, 1998(Cembella et al, , 1999 collected from the coastal waters of Nova Scotia, Canada. The causative organism of spirolide toxicity in shellfish was recently identified as A. ostenfeldii (Paulsen) Balech & Tangen (Cembella et al, 2000), and certain isolates of this species can produce a wide diversity of spirolides in unialgal batch culture (Hu et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Discrimination of the toxigenic dinoflagellatesAlexandrium tamarenseandA. ostenfeldiiin co-occurring natural populations from Scottish coastal waters

John

Cembella

Hummert³

et al. 2003

European Journal of Phycology

119

View full text Add to dashboard Cite

Blooms of the toxic dinoflagellate Alexandrium tamarense (Lebour) Balech, a known producer of potent neurotoxins associated with paralytic shellfish poisoning (PSP), are common annual events along the Scottish east coast. The cooccurrence of a second Alexandrium species, A. ostenfeldii (Paulsen) Balech & Tangen is reported in this study from waters of the Scottish east coast. The latter species has been suspected to be an alternative source of PSP toxins in northern Europe. Recent identification of toxic macrocyclic imines known as spirolides in A. ostenfeldii indicates a potential new challenge for monitoring toxic Alexandrium species and their respective toxins in natural populations. In mixed phytoplankton assemblages, A/exandrium species are difficult to discriminate accurately by convention~llight microscopy.Species-specific rRNA probes based upon 18S and 28S ribosomal DNA sequences were developed for A. ostenfeldii and tested by dot-blot and fluorescence in situ hybridization (FISH) techniques. Hybridization patterns of A. ostenfeldii probes for cultured A/exandrium isolates, and cells from field populations from the Scottish east coast, were compared with those of rONA probes fOf A. tamarense and a universal dinoflagellate probe. A/exandrium cell numbers in field samples determined by whole-cell in situ hybridization were much lower than those determined by optical microscopy with the Utermohl-~ethod involving sedimentation chambers, but the results were highly correlated (e.g. r 2 =0.94; n =6 for A. tamarense).Determination of spirolides and PSP toxins by instrumental analysis on board ship demonstrated the presence of both toxin groups in plankton assemblages collected from surface waters near the Orkney Islands, and confirmed the association of A. ostenfeldii with spirolides in northern Europe. These results show that rRNA probes for A. tamarense and A. ostenfe/dii are useful, albeit only semi-quantitative, tools to detect and discriminate these species in field studies.

show abstract

Section: Introductionmentioning

confidence: 99%

Discrimination of the toxigenic dinoflagellatesAlexandrium tamarenseandA. ostenfeldiiin co-occurring natural populations from Scottish coastal waters

John

Cembella

Hummert³

et al. 2003

European Journal of Phycology

119

View full text Add to dashboard Cite

show abstract

“…SPXs were first discovered and characterized in 1991 in cultured blue mussels (Mytilus edulis) and sea scallops (Placopecten magellanicus) in Nova Scotia, Canada (Hu et al 1996). Alexandrium ostenfeldii I peruvianum has been found in the United States (Gribble et al 2005) and in New Zealand (Mackenzie 2004).…”

Section: Spirolides (Spxs)mentioning

confidence: 99%

“…Toxicity of cyclic imines is currently under investigation because, despite the fact that they can be bio-transformed via detoxification by reduction (GYM) or by ring opening (SPX A and B) in molluscs (Hu et al 1996, Stewart et al 1997, Munday 2008, there is limited information regarding their absorption, distribution, metabolism and excretion in animals or in humans. Therefore, no conclusions could be drawn with respect to any possible risk to consumers of contaminated shellfish (EFSA 2010).…”

Section: Toxicity Of Cyclic Iminesmentioning

confidence: 99%

“…SPXs that contain an extra methyl group on the imine ring compared with spirolide A and Β resist enzymatic hydrolysis conditions in shellfish and, therefore, might pose a threat to consumers ). On the other hand, spirolides E and F, which are regarded as hydrolysis products of spirolides A and Β (Hu et al 1996(Hu et al , 2001, are biologically inactive ). This hypothesis is reinforced by the stability of the doublemethylated spirolides C and D under hydrolytic conditions in shellfish (Hu et al 2001).…”

Section: Spirolides (Spxs)mentioning

confidence: 99%

See 1 more Smart Citation

Cyclic imines, as emerging marine toxins: Chemical properties, distribution, toxicological aspects and detection methods

Chatzianastasiou¹,

Katikou²,

Zacharaki³

et al. 2017

J Hellenic Vet Med Soc

View full text Add to dashboard Cite

Shellfish and, specifically, bivalve molluscs are a food commodity of great nterest for both commercial and public health reasons. They consume microalgae from surrounding waters, which are generally beneficial for aquaculture, but they comprise certain toxin-producing species. These species produce marine toxins which, via the filter-feeding mechanism of bivalve molluscs, accumulate in their tissues. This accumulation is more intense andmore dangerous for public health during the so-called periods of Harmful Algal Blooms (HABs) when the microalgal population grows. According to their chemical structure, marine toxins are classified into 8 groups, one of which is the cyclic imines. These lipophilic toxins were accidentally discovered during routine bioassays for the detection of other lipophilic marine toxins due to the induction of neurological symptoms and acute death in mice. They include the following subgroups: Spirolides (SPX), gymnodimines (GYM), pinnatoxins (PnTX), pteriatoxins (PtTX), prorocentrolides and spiro-prorocentrimines. The European Union (EU) is more concerned about the first three subgroups, because, in contrast with the latter three, they have already been detected in Europe or there is strong evidence supporting their presence. Spirolides are produced by the dmof\a.ge\\ate Alexandrìum ostenfeldii/peruvianum, gymnodimines by the dinoflagellate Karenia selliformis and pinnatoxins by a peridinoid dinoflagellate recently described in the new genus Vulcanodinium spp.. Although there is insufficient information regarding the geographical distribution of cyclic imines, the fact that they have been detected on multiple occasions in European waters, in combination with their aforementioned acute toxicity in mice after intraperitoneal injection, has established them, at least within the EU, as a topic of profound scientific research. In spite of their acute toxicity in mice, no incident of human intoxication has been attributed to cyclic imines. Presently, the EU has neither set any Maximum Permissible Limits for the concentration of cyclic imines in shellfish nor appointed any reference method for their detection and quantification. Currently, the methods applied are biological, biochemical and chemical. The biological method is a bioassay, which is conducted via the intraperitoneal injection of mice with an extract containing the compound under examination and it detects total toxicity. This properly is essential for the detection of unknown toxins, but the use of laboratory animals raises serious ethical concerns and animal welfare issues. The biochemical method is based on competition between cyclic imines and a fluorescently labelled compound for binding to receptors of the electric ray Torpedo marmorata. Finally, in respect of chemical methods, liquid chromatography with tandem mass spectrometry detection (LC-MS/MS) is the most significant method because it is fast, of high repeatability and specificity.

show abstract

“…to date, 3 classes of SPx (A-D, e-F, and G, H, I) and 34 GYM analogues (A, B, C) and 12-methyl gymnodimine have been identified. SPX-C and SPX-D appear to be resistant to acidic and enzymatic degradation in shellfish, while SPX-E and SPX-F could be metabolites of SPx-A and SPx-B (Christian et al, 2008;Hu et al, 1996). the characteristic of CI is the presence of an imine moiety as part of a bicyclic ring system (Fig.…”

Section: Diarrheic Shellfish Poisoning (Dsp) Toxinsmentioning

confidence: 99%

A roadmap for hazard monitoring and risk assessment of marine biotoxins on the basis of chemical and biological test systems

Daneshian

2013

ALTEX

View full text Add to dashboard Cite

Summary Aquatic food accounts for over 40% of global animal food products, and the potential contamination with toxins of algal origin -marine biotoxins -poses a health threat for consumers. The gold standards to assess toxins in aquatic food have traditionally been in vivo methodssingle marine biotoxins or combinations of marine biotoxins and intoxication symptomatology as well as monitoring the "success" of controls implemented during fishery and aquaculture production, processing, and retailing. For this reason, a workshop was organized in ermatingen, Switzerland by the Center for Alternatives to Animal testing -europe (CAAteurope) within the framework of the transatlantic think tank for toxicology (t 4 ).In contrast to other food products where hygiene and potential contamination with microbes or mold toxins is the prime issue, the emphasis in aquatic products (shellfish and finfish) is, beyond viral and bacterial contaminations, primarily placed on potential contamination with marine biotoxins owing to the numerous and recurring human intoxications.The gold standards to assess toxins in aquatic food have traditionally been in vivo methods, i.e., the mouse and the rat bioassays. Besides the ethical issues of in vivo bioassays there are specific difficulties, e.g., different exposure route (i.p. versus oral), low inter-species comparability, high intra-species variability, and questionable extrapolation of quantitative risk to humans, thus highlighting the need for the development of more reliable detection and quantification methods. Based on this reasoning, the european Food Safety Authority (eFSA) advocates the use of an analytical method, i.e., LC-MS (Liquid Chromatography coupled Mass Spectrometry), as a substitute for in vivo bioassays for almost all classes of marine toxins. However, although lC-MS is a very sensitive method that has the advantages of being able to detect multiple toxins in a single analysis and being good for confirming the identity of toxins, the quality of quantitative analysis is dependent on the availability of calibration standards. While many new toxin structural analogues have been detected and identified using LC-MS, this technique -as with most other methods -is not good at detecting new toxin types. When new toxin analogues are detected but accurate standards are not yet available, only an approximate quantitation is possible using estimated response factors.For the purpose of risk assessment of food, however, it is imperative to focus on the possible adverse effects, independent of whether they stem from one toxin or a combination of toxins. As toxicity is defined by functional and structural changes of biological systems, the development of a human-relevant in vitro system for appropriate risk assessment of marine biotoxins in seafood stands to reason. Moreover, poor correlation of human intoxications, of acute symptomatology and long-term adverse effects, and of predictive in vitro, in vivo, and analytical detection methodologies of marine biotoxins stems not least from a...

show abstract

Characterization of biologically inactive spirolides E and F: Identification of the spirolide pharmacophore

Cited by 136 publications

References 5 publications

Discrimination of the toxigenic dinoflagellatesAlexandrium tamarenseandA. ostenfeldiiin co-occurring natural populations from Scottish coastal waters

Discrimination of the toxigenic dinoflagellatesAlexandrium tamarenseandA. ostenfeldiiin co-occurring natural populations from Scottish coastal waters

Cyclic imines, as emerging marine toxins: Chemical properties, distribution, toxicological aspects and detection methods

A roadmap for hazard monitoring and risk assessment of marine biotoxins on the basis of chemical and biological test systems

Contact Info

Product

Resources

About