Behari J R, Nihal (nee Misra) M
Industrial Toxicology Research Centre, Lucknow, India.
Ind Health. 2000 Oct;38(4):408-12. doi: 10.2486/indhealth.38.408.
In this study an attempt has been made to examine the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) using galactosylated liposomes as carriers for mobilization of cadmium from the body of mice preexposed to cadmium chloride (0.005 mmoles/kg intraperitoneally daily for 4 days). Cadmium-exposed mice after a rest period of 8 weeks were administered DMSA intravenously, two injections 15 micromoles/kg with an interval of 48 h, as free form of DMSA, or DMSA encapsulated in liposomes composed of phosphatidyl choline, cholesterol and phosphatidyl ethanolamine (7:2:1; PC-lip-DMSA) or in liposomes to which p-aminophenyl galactoside had been anchored (Gal-lip-DMSA). Excretion of cadmium through urine and feces was monitored for 5 days. Thereafter animals were sacrificed, liver, kidneys, spleen and isolated hepatocytes were analysed for cadmium, copper and zinc concentration. Efficacy for cadmium mobilization from the body was found to be in the order Gal-lip-DMSA>PC-lip-DMSA>DMSA. These results show that liposomes can be used as targeted carrier system for chelating agents safely and efficiently as compared to administration of free chelating agent.
在本研究中,已尝试使用半乳糖基化脂质体作为载体,来检验中-2,3-二巯基丁二酸(DMSA)从预先暴露于氯化镉(每天腹腔注射0.005毫摩尔/千克,共4天)的小鼠体内动员镉的功效。经过8周的休息期后,给镉暴露小鼠静脉注射DMSA,以游离形式的DMSA或封装在由磷脂酰胆碱、胆固醇和磷脂酰乙醇胺组成的脂质体(7:2:1;PC-脂质体-DMSA)或对氨基苯基半乳糖苷已锚定的脂质体(半乳糖脂质体-DMSA)中,每15微摩尔/千克注射两次,间隔48小时。监测5天内镉通过尿液和粪便的排泄情况。此后处死动物,分析肝脏、肾脏、脾脏和分离的肝细胞中的镉、铜和锌浓度。发现从体内动员镉的功效顺序为:半乳糖脂质体-DMSA>PC-脂质体-DMSA>DMSA。这些结果表明,与游离螯合剂给药相比,脂质体可用作螯合剂的靶向载体系统,安全且有效。