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Published on: August 16, 2018
Toxicity Equivalency Factors for Tetrodotoxin Analogues Determined with Automated Patch Clamp on Voltage-Gated Sodium
Jaume Reverté1,2, Maria Rambla-Alegre1, Andres Sanchez-Henao1,3
1IRTA, Ctra, Poble Nou km 5.5, 43540 La Ràpita, Spain.
Abstract:
Tetrodotoxin (TTX) is a potent marine neurotoxin, responsible for numerous poisoning incidents and some human fatalities. To date, more than 30 TTX analogues have been identified, but their individual toxicities and roles in poisoning remain largely unknown. In this work, the toxicity equivalency factors (TEFs) of five TTX analogues were determined by assessing the blockade of voltage-gated sodium channels in Neuro-2a cells using automated patch clamp (APC). All TTX analogues were less toxic than TTX. The derived TEFs were applied to the individual TTX analogues concentrations measured in pufferfish samples, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A comparison of these results with those obtained from APC analysis demonstrated that TEFs can be effectively used to translate LC-MS/MS analytical data into meaningful toxicological information. This is the first study to utilize APC device for the toxicological assessment of TTX analogues, highlighting its potential as a bioanalytical tool for seafood safety management and human health protection.
Insights
Tetrodotoxin (TTX) and its analogues are marine toxins. This study determined the toxicity equivalency factors (TEFs) of five TTX analogues using automated patch clamp, finding them less toxic than TTX, aiding seafood safety.
Area of Science:
- Marine toxicology
- Neuroscience
- Analytical chemistry
Background:
- Tetrodotoxin (TTX) is a potent marine neurotoxin causing human poisonings.
- Over 30 TTX analogues exist, but their toxicities and roles in poisoning are largely unknown.
- Accurate toxicological assessment is crucial for seafood safety.
Purpose of the Study:
- To determine the toxicity equivalency factors (TEFs) of five TTX analogues.
- To assess the utility of automated patch clamp (APC) for toxicological evaluation of TTX analogues.
- To translate analytical data into meaningful toxicological information for seafood safety.
Main Methods:
- Automated patch clamp (APC) was used to assess the blockade of voltage-gated sodium channels by TTX analogues.
- Toxicity equivalency factors (TEFs) were derived for five TTX analogues.
- Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) measured analogue concentrations in pufferfish.
- TEFs were applied to LC-MS/MS data for toxicological interpretation.
Main Results:
- All five TTX analogues exhibited lower toxicity than TTX.
- TEFs were successfully derived for the studied TTX analogues.
- TEFs effectively translated LC-MS/MS data into toxicological insights.
- APC proved effective for toxicological assessment of TTX analogues.
Conclusions:
- TTX analogues are less toxic than TTX, but require toxicological evaluation.
- TEFs are valuable for assessing the toxicological impact of TTX analogues in seafood.
- Automated patch clamp (APC) is a promising bioanalytical tool for seafood safety management and human health protection.
- This study provides a framework for assessing TTX analogue toxicity in marine ecosystems.
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