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Chronic Toxicity Study of Neosaxitoxin in Rats

Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks wit...

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Autores principales: Zepeda, Ramiro J., Candiracci, Manila, Lobos, Nicolas, Lux, Sebastian, Miranda, Hugo F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178483/
https://www.ncbi.nlm.nih.gov/pubmed/25257789
http://dx.doi.org/10.3390/md12095055
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author Zepeda, Ramiro J.
Candiracci, Manila
Lobos, Nicolas
Lux, Sebastian
Miranda, Hugo F.
author_facet Zepeda, Ramiro J.
Candiracci, Manila
Lobos, Nicolas
Lux, Sebastian
Miranda, Hugo F.
author_sort Zepeda, Ramiro J.
collection PubMed
description Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic.
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spelling pubmed-41784832014-10-02 Chronic Toxicity Study of Neosaxitoxin in Rats Zepeda, Ramiro J. Candiracci, Manila Lobos, Nicolas Lux, Sebastian Miranda, Hugo F. Mar Drugs Article Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. MDPI 2014-09-25 /pmc/articles/PMC4178483/ /pubmed/25257789 http://dx.doi.org/10.3390/md12095055 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zepeda, Ramiro J.
Candiracci, Manila
Lobos, Nicolas
Lux, Sebastian
Miranda, Hugo F.
Chronic Toxicity Study of Neosaxitoxin in Rats
title Chronic Toxicity Study of Neosaxitoxin in Rats
title_full Chronic Toxicity Study of Neosaxitoxin in Rats
title_fullStr Chronic Toxicity Study of Neosaxitoxin in Rats
title_full_unstemmed Chronic Toxicity Study of Neosaxitoxin in Rats
title_short Chronic Toxicity Study of Neosaxitoxin in Rats
title_sort chronic toxicity study of neosaxitoxin in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178483/
https://www.ncbi.nlm.nih.gov/pubmed/25257789
http://dx.doi.org/10.3390/md12095055
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