Chronic toxicity study of neosaxitoxin in rats

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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5055-5071
Number of pages17
JournalMarine Drugs
Volume12
Issue number9
DOIs
Publication statusPublished - 1 Sept 2014

Keywords

  • Acute toxicity
  • Chronic toxicity
  • Marine toxin
  • Neosaxitoxin

ASJC Scopus subject areas

  • Drug Discovery

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