Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage
Fan Wang1, Fuhai Zhang1, Juxingsi Song1
1Department of Marine Biomedicine and Polar Medicine, Naval Special Medical Center, Naval Medical University, Shanghai 200433, China.
Abstract:
Tetrodotoxin (TTX) is a highly fatal marine biotoxin. Constantly increasing intoxications and the lack of specific antitoxic drugs in clinical applications highlight the need for further research into the toxic effects of TTX. Current reports on poisoning cases and the TTX toxicity mechanism suggest that the blocking of voltage-gated sodium channels (VGSCs) by TTX is probably reversible, but direct evidence of this is lacking, as far as we are aware. This study explored the acute toxic effects of TTX at sub-lethal doses via different routes, analyzing variations in muscle strength and TTX concentration in the blood in mice. We found that the loss of muscle strength in mice caused by TTX was dose-dependent and reversible, and the death time and muscle strength variations after oral gavage with TTX appeared to occur later and were more variable than those after intramuscular injection. In conclusion, we systematically compared the acute toxic effects of TTX for two different administration routes at sub-lethal doses, directly verifying the reversible reaction of TTX blocking VGSCs and speculating that averting a complete block of VGSCs by TTX could be an effective strategy for preventing death from TTX poisoning. This work may provide data for the diagnosis and treatment of TTX poisoning.
Insights
Tetrodotoxin (TTX) poisoning in mice showed dose-dependent and reversible muscle weakness. This study provides evidence that TTX
Area of Science:
- Marine Biotoxins
- Neurotoxicology
- Pharmacology
Background:
- Tetrodotoxin (TTX) is a potent marine neurotoxin causing severe human intoxications.
- Clinical treatments for TTX poisoning are limited, necessitating further research into its toxic mechanisms.
- The reversibility of TTX's blockade of voltage-gated sodium channels (VGSCs) remains under-investigated.
Purpose of the Study:
- To investigate the acute toxic effects of sub-lethal Tetrodotoxin doses in mice.
- To compare the impact of different administration routes (oral vs. intramuscular) on TTX toxicity.
- To provide direct evidence for the reversibility of TTX-induced VGSC blockade.
Main Methods:
- Administration of sub-lethal doses of TTX to mice via oral gavage and intramuscular injection.
- Monitoring of muscle strength variations in TTX-exposed mice.
- Quantification of TTX blood concentrations in relation to observed toxic effects.
Main Results:
- TTX-induced muscle weakness in mice was found to be dose-dependent and reversible.
- Intramuscular injection of TTX resulted in more rapid and less variable onset of toxic effects compared to oral gavage.
- Direct evidence supporting the reversible nature of TTX's interaction with VGSCs was obtained.
Conclusions:
- The study confirms the reversible blockade of VGSCs by Tetrodotoxin, offering insights into TTX toxicity.
- Comparing administration routes reveals differences in TTX's acute toxicological profile.
- Averting complete VGSC blockade by TTX may be a viable strategy for preventing fatal poisoning.
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