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Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage.

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.

SUBMITTER: Wang F

PROVIDER: S-EPMC10220813 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage.

Wang Fan F Zhang Fuhai F Song Juxingsi J Zou Shuaijun S Li Jie J Huang Yichao Y Zhang Liming L Wang Qianqian Q

Toxins 20230513 5

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 o ...[more]

PMID: 37235368

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Project description:Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune responses. In this study, we conducted a head-to-head comparison of immune response and safety of inactivated rabies vaccine inoculated via intraperitoneal (IP), intramuscular (IM), subcutaneous (SC) and needle-free injection technology-based intradermal (ID) routes in ICR mice. Immune response was assessed in terms of antigen-specific antibodies, antibody subtypes and neutralizing antibodies for up to 28 weeks. A live rabies virus challenge was also carried out to evaluate vaccine potency. The dynamics of inflammatory cell infiltration at the skin and muscle levels were determined via histopathological examination. The kinetics and distribution of a model antigen were also determined by using in vivo fluorescence imaging. Evidence is presented that the vaccine inoculated via the ID route resulted in the highest antigen-specific antibody and neutralizing antibody titers among all administration routes, while IP and IM routes were comparable, followed by the SC route. Antibody subtype analysis shows that the IP route elicited a Th1-biased immune response, while SC and IM administration elicited a prominent Th2-type immune response. Unexpectedly, the ID route leads to a balanced Th1 and Th2 immune response. In addition, the ID route conferred effective protection against lethal challenge with 40 LD50 of the rabies CVS strain, which was followed by IP and IM routes. Moreover, a one-third dose of the vaccine inoculated via the ID route provided comparable or higher efficacy to a full dose of the vaccine via the other three routes. The superior performance of ID inoculation over other routes is related to longer local retention at injection sites and higher lymphatic drainage. Histopathology examination reveals a transient inflammatory cell infiltration at ID and IM injection sites which peaked at 48 h and 24 h, respectively, after immunization, with all side effects disappearing within one week. These results suggest that needle-free injection technology-based ID inoculation is a promising strategy for rabies vaccination in regard to safety and efficacy.

Dataset Information

Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage.

Publications

Acute Toxic Effects of Tetrodotoxin in Mice via Intramuscular Injection and Oral Gavage.

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