Yu Gao-yan, Yan Chong-huai, Yu Xiao-gang, Zuo Yong, Zou Xiang-yu, Xu Jian, Wu Sheng-hu, Shen Xiao-ming
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai Key Laboratory of Children's Environmental Health, Shanghai 200092, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2009 Jan;43(1):8-13.
To explore the effect of chelation therapy with succimer (DMSA) in male rabbits of moderate lead poisoning during juvenile stage.
Twenty-four 45-day-old male New Zealand rabbits were randomly divided into three groups (therapy group, TG; positive control group, PG and negative control group, NG, n=8). The TG and PG were orally exposed to lead acetate (5 mg x kg(-1) x d(-1)) for 6 weeks. Rabbits in TG were orally supplied DMSA 1050 mg/m2 in the first week and 700 mg/m2 in the next two weeks, while the other two groups wren't blood and urinary samples of all rabbits were collected per week. The tissues and organs of all rabbits were collected after 12 weeks. The blood lead levels (BLLs) were determined by atomic absorption spectrometer. The urine lead levels and the lead contents of tissue and organ were determined by inductively coupled plasma-mass spectrometry. Histopathology of tissue and organ was observed by light microscope.
Compared with PG, the lead level in the morning urine of TG with DMSA chelating was increased significantly. The level was peaked at (1246.96 +/- 157.91) microg/L on the first day after chelating. While the base line was (40.97 +/- 1.77) microg/L before chelating. Meanwhile, the BLLs were sharply declined from (429.63 +/- 10.82) microg/L to (238.50 +/- 11.82) microg/L. The urine lead levels of TG decreased through the 3-week chelating and 3-week discontinuation. The urine lead levels of these two groups were significantly different (F=2934.35, P<0.01). Compared to each two groups in these three groups, there were significant difference (P<0.01). The authors found the reversion of BLLs in first week after stop chelating. The BLLs of PG presented the slow course of declining in the same time, were (135.50 +/- 7.09) microg/L, very close to the level of TG for (149.88 +/- 11.39) microg/L. Compared with treatment discontinuation for 3 weeks, the urine lead levels and the body weight gain of the therapy group increased more than that of PG, and the BLLs and the lead concentrations in tissues and organs decreased more than that of PG, and histopathology in the liver tissues and testicle tissues were improved.
DMSA chelating for the rodent models of moderate lead poisoning might reduce the BLLs and soft tissue lead contents quickly and effectively, decrease toxic effects of lead in a short period of time, thus alleviate the impairment of lead poisoning on tissues and organs by decreasing lead burden, and bring out improvement on the growth retardation caused by lead poisoning.
探讨二巯基丁二酸（DMSA）螯合疗法对幼年期雄性中度铅中毒家兔的影响。
将24只45日龄雄性新西兰家兔随机分为三组（治疗组，TG；阳性对照组，PG；阴性对照组，NG，n = 8）。TG组和PG组经口给予醋酸铅（5 mg·kg⁻¹·d⁻¹），持续6周。TG组家兔在第1周经口给予DMSA 1050 mg/m²，在接下来的两周给予700 mg/m²，而其他两组未给予。每周采集所有家兔的血液和尿液样本。12周后采集所有家兔的组织和器官。采用原子吸收光谱仪测定血铅水平（BLLs）。采用电感耦合等离子体质谱法测定尿铅水平以及组织和器官中的铅含量。通过光学显微镜观察组织和器官的组织病理学变化。
与PG组相比，采用DMSA螯合的TG组晨尿中的铅水平显著升高。螯合后第1天该水平达到峰值（1246.96 ± 157.91）μg/L，而螯合前基线水平为（40.97 ± 1.77）μg/L。同时，BLLs从（429.63 ± 10.82）μg/L急剧下降至（238.50 ± 11.82）μg/L。TG组的尿铅水平在3周螯合期和3周停药期均下降。这两组的尿铅水平差异有统计学意义（F = 2934.35，P < 0.01）。与这三组中的任意两组相比，差异均有统计学意义（P < 0.01）。作者发现停药后第1周BLLs出现回升。PG组的BLLs在同一时间呈缓慢下降过程，为（135.50 ± 7.09）μg/L，非常接近TG组的水平（149.88 ± 11.39）μg/L。与停药3周相比，治疗组的尿铅水平和体重增加量比PG组增加更多，BLLs以及组织和器官中的铅浓度比PG组下降更多，并且肝组织和睾丸组织的组织病理学得到改善。
DMSA螯合疗法对中度铅中毒的啮齿动物模型可能快速有效地降低BLLs和软组织中的铅含量，在短时间内降低铅的毒性作用，从而通过减轻铅负荷缓解铅中毒对组织和器官的损害，并改善铅中毒所致的生长发育迟缓。
