Naseem S M
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5001, USA.
Toxicol Appl Pharmacol. 1996 Nov;141(1):49-58. doi: 10.1006/taap.1996.0259.
This study evaluated the toxicokinetics of a saxitoxin (STX) analog, [3H]saxitoxinol (STXOL), in rats. [3H]saxitoxinol (18.9 microCi/kg body weight) was administered iv to male Wistar rats via the penile vein. After injection, [3H]STXOL disappeared rapidly from plasma (t 1/2 = 29.3 min), and 75% of the radiolabel was cleared from plasma within 2 hr. Radioactivity associated with red blood cell membranes was inversely related with the radioactivity associated with hemoglobin, suggesting internalization of STXOL. Distribution of [3H]STXOL, 48 hr after iv exposure, showed that muscle tissues retained 91.2 +/- 7.1%, liver 63.7 +/- 3.8%, heart 17.4 +/- 1.6%, and lung 9.2 +/- 0.8% of the residual dose. High-performance liquid chromatography (HPLC) analysis for saxitoxinol showed three to four major radiolabeled peaks for each of these tissues. By 48 hr, radiolabel associated with the saxitoxinol peak decreased 95% in lungs, heart, and kidneys, with a concomitant increase in unidentified, more polar peaks. No STXOL metabolites were detected in the urine from these animals. Radioactivity accumulation in the brain increased to a maximum of 162% at 8-hr postexposure, compared to values obtained at 10 min, then gradually declined to 148% by 48 hr. HPLC analysis of brain extracts showed that the relative percentage of radioactivity associated with parent toxin gradually decreased, with a concomitant rise in the levels of more polar peaks. Similar results were obtained for spinal cord. The data suggest that saxitoxinol was rapidly cleared from most of the peripheral organs and was little, if any metabolized by muscle cells.
本研究评估了一种麻痹性贝类毒素（STX）类似物[³H]石房蛤毒素醇（STXOL）在大鼠体内的毒代动力学。通过阴茎静脉向雄性Wistar大鼠静脉注射[³H]石房蛤毒素醇（18.9微居里/千克体重）。注射后，[³H]STXOL迅速从血浆中消失（t 1/2 = 29.3分钟），75%的放射性标记物在2小时内从血浆中清除。与红细胞膜相关的放射性与与血红蛋白相关的放射性呈负相关，表明STXOL发生了内化。静脉注射暴露48小时后，[³H]STXOL的分布显示，肌肉组织保留了91.2±7.1%的残留剂量，肝脏保留了63.7±3.8%，心脏保留了17.4±1.6%，肺保留了9.2±0.8%。对石房蛤毒素醇的高效液相色谱（HPLC）分析表明，这些组织中的每一个都有三到四个主要的放射性标记峰。到48小时时，与石房蛤毒素醇峰相关的放射性在肺、心脏和肾脏中减少了95%，同时未鉴定的、极性更强的峰增加。在这些动物的尿液中未检测到STXOL代谢物。与暴露10分钟时的值相比，暴露后8小时大脑中的放射性积累增加到最大值的162%，然后到48小时逐渐下降到148%。大脑提取物的HPLC分析表明，与母体毒素相关的放射性相对百分比逐渐降低，同时极性更强的峰的水平升高。脊髓也得到了类似的结果。数据表明，石房蛤毒素醇从大多数外周器官中迅速清除，并且肌肉细胞对其代谢极少，如果有代谢的话。
