Chronic toxicity study of neosaxitoxin in rats

Ramiro J. Zepeda, Manila Candiracci, Nicolas Lobos, Sebastian Lux, Hugo F. Miranda

Resultado de la investigación: Article

5 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)5055-5071
Número de páginas17
PublicaciónMarine Drugs
Volumen12
N.º9
DOI
EstadoPublished - 1 sep 2014

Huella dactilar

Voltage-Gated Sodium Channel Blockers
Aspartate Aminotransferases
Local Anesthetics
Bilirubin
neosaxitoxin
Suspensions
Eating
Body Weight
Clinical Trials
Weights and Measures
Control Groups

ASJC Scopus subject areas

  • Drug Discovery
  • Medicine(all)

Citar esto

Zepeda, R. J., Candiracci, M., Lobos, N., Lux, S., & Miranda, H. F. (2014). Chronic toxicity study of neosaxitoxin in rats. Marine Drugs, 12(9), 5055-5071. https://doi.org/10.3390/md12095055
Zepeda, Ramiro J. ; Candiracci, Manila ; Lobos, Nicolas ; Lux, Sebastian ; Miranda, Hugo F. / Chronic toxicity study of neosaxitoxin in rats. En: Marine Drugs. 2014 ; Vol. 12, N.º 9. pp. 5055-5071.
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Zepeda, RJ, Candiracci, M, Lobos, N, Lux, S & Miranda, HF 2014, 'Chronic toxicity study of neosaxitoxin in rats', Marine Drugs, vol. 12, n.º 9, pp. 5055-5071. https://doi.org/10.3390/md12095055

Chronic toxicity study of neosaxitoxin in rats. / Zepeda, Ramiro J.; Candiracci, Manila; Lobos, Nicolas; Lux, Sebastian; Miranda, Hugo F.

En: Marine Drugs, Vol. 12, N.º 9, 01.09.2014, p. 5055-5071.

Resultado de la investigación: Article

TY - JOUR

T1 - Chronic toxicity study of neosaxitoxin in rats

AU - Zepeda, Ramiro J.

AU - Candiracci, Manila

AU - Lobos, Nicolas

AU - Lux, Sebastian

AU - Miranda, Hugo F.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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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KW - Chronic toxicity

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Zepeda RJ, Candiracci M, Lobos N, Lux S, Miranda HF. Chronic toxicity study of neosaxitoxin in rats. Marine Drugs. 2014 sep 1;12(9):5055-5071. https://doi.org/10.3390/md12095055