Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication:: kinetics and trials to enhance elimination in two patients
Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication:: kinetics and trials to enhance elimination in two patients
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DOI：
10.1007/s00204-002-0345-7
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发表时间：
2002-06-01
影响因子：
6.1
通讯作者：
Abraham, K
中科院分区：
文献类型：
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作者：
Geusau, A;Schmaldienst, S;Abraham, K
1998年春，两名妇女被诊断为严重的2，3，7，8-四氯二苯并对二恶英（TCDD）中毒。在接下来的3年里，TCDD水平进行了监测，在各种尝试，以提高其消除，并评估了半衰期。Olestra是一种不可消化、不可吸收的膳食脂肪替代品，以纯物质或马铃薯片形式持续给予患者。此外，在更严重的污染患者中，我们研究了低密度脂蛋白（LDL）-单采术，一种体外血脂消除方法，是否能有效降低TCDD的身体负担。在1998年春季，首次测量的血液浓度为144，000 pg/g血脂，患者1和26，000 pg/g患者2，这是在成人中测量的最高水平。2001年3月，血脂浓度为35，900和9，500 pg/g，对应于患者I的560天（1.5年）和患者2的1050天（2.9年）的总消除半衰期，这大大短于背景和中度暴露水平报告的7-9年中位值。通过计算TCDD的半衰期和测量TCDD通过不同途径的消除，可以计算出一种未知的消除途径，分别占患者I和2的总消除量的78%和62%，可能是由于高TCDD暴露引起的诱导肝脏代谢。如前所述，olestra的管理被认为是有效的，在增加粪便排泄的TCDD。由于在我们的患者中半衰期较短，olestra对总体消除的影响相对较小，但预计对于“正常”半衰期要大得多。LDL-单采术显示消除TCDD，对应于消除的血脂。当每周使用两次时，通过这种方法排泄的TCDD量与粪便排泄量相当。考虑到所涉及的成本和时间，LDL单采术似乎不适合用于增强TCDD消除。
In spring 1998, two women were diagnosed with severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication. Over the following 3 years, TCDD levels were monitored under various attempts to enhance its elimination, and the half-lives were evaluated. Olestra, a non-digestible, non-absorbable dietary fat substitute, was continuously administered to the patients either as pure substance or in potato-chips. Additionally, in the more severely contaminated patient, we studied whether low-density lipoprotein (LDL)-apheresis, an extracorporeal means of blood lipid elimination, was effective in reducing the TCDD body burden. The blood concentrations initially measured in spring 1998 were 144,000 pg/g blood fat in patient I and 26,000 pg/g in patient 2, the highest levels ever measured in adults. In March 200 1, concentrations in blood fat were 35,900 and 9,500 pg/g, corresponding to overall elimination half-lives of 560 days (1.5 years) in patient I and 1050 days (2.9 years) in patient 2, which are considerably shorter than median values of 7-9 years reported for background and moderate exposure levels. Calculations of the TCDD half-lives and measurements of TCDD elimination via different routes allowed the calculation of an unidentified route of elimination, representing 78 and 62% of the overall elimination in patient I and 2, respectively, probably due to an induced hepatic metabolism caused by the high TCDD exposure. As previously reported, administration of olestra was found to be effective in increasing the fecal excretion of TCDD. Due to the short half-lives in our patients, the effect of olestra on the overall elimination was relatively small, but is expected to be much greater for 'normal' half-lives. LDL-apheresis was shown to eliminate TCDD, corresponding to the eliminated blood fat. When employed twice a week, the amount of TCDD excreted by this method was comparable to fecal excretion. In view of costs and time involved, LDL-apheresis does not seem to be justified for enhancement of TCDD elimination.