Levitskaia Tatiana G, Creim Jeffrey A, Curry Terry L, Luders Teresa, Morris James E, Sinkov Sergei I, Woodstock Angela D, Thrall Karla D
Pacific Northwest National Laboratory, PO Box 999, MSIN P7-22, Richland, WA 99352, USA.
Health Phys. 2009 Aug;97(2):115-24. doi: 10.1097/01.HP.0000346798.82764.d7.
With the increased threat of terrorist release of radioactive materials, there is a need for non-toxic decorporation agents to treat internal contamination with radionuclides. In this study, low molecular weight chitosan was evaluated for decorporation of radioactive cobalt (60Co). The affinity of chitosan for Co(II) was tested in vitro using spectrophotometric and potentiometric titration techniques. For in vivo studies, the effect of chitosan on ingested 60Co was evaluated using F344 rats administered a single dose followed by oral chitosan. Chitosan was also evaluated for systemic decorporation of 60Co following intravenous injection with repeated chitosan administration over 5 d. Control animals received 60Co without chelation treatment. Excreta and tissues were collected for analysis using gamma-counting techniques. Results from in vitro experiments confirmed the binding of Co(II) to chitosan, with the postulated formation of a mixed cobalt-chitosan-hydroxide complex species; a stability constant was calculated for this complex. For in vivo studies, oral administration of chitosan significantly reduced systemic absorption of orally administered 60Co as evidenced by an increase in fecal elimination and decrease in urinary elimination. However, oral administration of chitosan lactate slightly decreased fecal excretion of 60Co. Further, oral administration of chitosan significantly reduced 60Co levels in kidney, liver, and skeleton compared to control animals receiving 60Co alone. By the i.v. route, chitosan slightly reduced levels of 60Co in tissues compared to controls, although statistically significant reductions were only observed for blood and kidney. Overall, this commercially available chitosan oligosaccharide exhibited promising potential; further studies are warranted to evaluate the optimal dosing regimen and chemical modifications to increase effectiveness.
随着放射性物质被恐怖分子释放的威胁增加，需要无毒的促排剂来治疗放射性核素的体内污染。在本研究中，对低分子量壳聚糖进行了放射性钴（60Co）促排作用的评估。使用分光光度法和电位滴定技术在体外测试了壳聚糖对Co（II）的亲和力。对于体内研究，使用给予单剂量60Co随后口服壳聚糖的F344大鼠评估壳聚糖对摄入的60Co的影响。还评估了壳聚糖在静脉注射并在5天内重复给予壳聚糖后对60Co的全身促排作用。对照动物接受60Co但不进行螯合治疗。收集排泄物和组织，使用γ计数技术进行分析。体外实验结果证实了Co（II）与壳聚糖的结合，并推测形成了混合的钴 - 壳聚糖 - 氢氧化物络合物物种；计算了该络合物的稳定常数。对于体内研究，口服壳聚糖显著降低了口服60Co的全身吸收，粪便排泄增加和尿液排泄减少证明了这一点。然而，口服乳酸壳聚糖略微降低了60Co的粪便排泄。此外，与仅接受60Co的对照动物相比，口服壳聚糖显著降低了肾脏、肝脏和骨骼中的60Co水平。通过静脉注射途径，与对照组相比，壳聚糖略微降低了组织中60Co的水平，尽管仅在血液和肾脏中观察到统计学上显著的降低。总体而言，这种市售的壳寡糖显示出有前景的潜力；有必要进一步研究以评估最佳给药方案和化学修饰以提高有效性。
