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Mar. Drugs 2014, 12(9), 5055-5071; doi:10.3390/md12095055

Chronic Toxicity Study of Neosaxitoxin in Rats

1
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Medical School, University of Chile, Independencia 1027, 8380453 Santiago, Chile
2
School of Medicine, ICBM, Medical School, Universidad de Chile, Independencia 1027, 8380453 Santiago, Chile
3
Anesthesia Department, Brigham and Woman's Hospital, Harvard University, 75 Francis Street, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Received: 29 January 2014 / Revised: 6 June 2014 / Accepted: 7 July 2014 / Published: 25 September 2014
(This article belongs to the Special Issue Alkaloid Analogs)
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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. View Full-Text
Keywords: neosaxitoxin; marine toxin; chronic toxicity; acute toxicity neosaxitoxin; marine toxin; chronic toxicity; acute toxicity
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MDPI and ACS Style

Zepeda, R.J.; Candiracci, M.; Lobos, N.; Lux, S.; Miranda, H.F. Chronic Toxicity Study of Neosaxitoxin in Rats. Mar. Drugs 2014, 12, 5055-5071.

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