Zepeda Ramiro J, Candiracci Manila, Lobos Nicolas, Lux Sebastian, Miranda Hugo F
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Medical School, University of Chile, Independencia 1027, 8380453 Santiago, Chile.
Anesthesia Department, Brigham and Woman's Hospital, Harvard University, 75 Francis Street, Boston, MA 02115, USA.
Mar Drugs. 2014 Sep 25;12(9):5055-71. doi: 10.3390/md12095055.
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.
新石房蛤毒素（NeoSTX）是可兴奋细胞上电压门控钠通道的一种特异性可逆阻滞剂。在过去十年中，它已在多项有趣的临床试验中进行了测试，然而关于其对哺乳动物毒性的信息仍然很少。用1、3或6μg/kg皮下注射剂量的NeoSTX对大鼠进行12周治疗。在第12周和第17周，处死动物并采集血样进行血液学和生化分析。摘取器官进行重量测定和组织病理学评估。腹腔内（ip）给药的最低急性毒性为（30.35μg/kg），肌肉注射和皮下注射途径之间无显著差异（分别为11.4和12.41μg/kg）。在第12周和停药五周后，NeoSTX给药未产生致死性。腹腔注射6μg/kg NeoSTX在第12周时导致体重和食物摄入量降低（p<0.05），总胆红素、直接胆红素、γ-谷氨酰转移酶（GGT）和谷草转氨酶（SGOT）的血液水平升高；在恢复期所有这些指标均恢复正常。腹腔注射1和3μg/kg NeoSTX与对照组相比未显示出显著变化。所有组的组织病理学表现均正常。本研究表明，NeoSTX在体内是安全的，为其作为局部麻醉剂使用提供了可靠的安全范围。
