Marija Varnai Veda, Piasek Martina, Blanusa Maja, Matek Sarić Marijana, Juresa Dijana, Kostial Krista
Mineral Metabolism Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
J Appl Toxicol. 2004 Mar-Apr;24(2):123-8. doi: 10.1002/jat.961.
The effect of combined treatment with meso-2,3-dimercaptosuccinic acid (DMSA) and calcium supplementation in reducing lead absorption and enhancing lead elimination was evaluated in suckling rats under two experimental conditions: during ongoing oral lead exposure (lead acetate, 2 mg Pb kg(-1) day(-1), total dose 16 mg Pb kg(-1)) or after lead exposure (72 h after a 2-day lead exposure, total dose 12 mg Pb kg(-1) s.c.). The artificial feeding method was used for calcium supplementation, with 6% Ca (as CaHPO(4)) suspension in cow's milk to increase the daily calcium intake about three times above control values. Artificial feeding lasted for 7 h a day over eight consecutive days. During this period DMSA was administered on 6 days twice a day (0.5 mmol kg(-1) day(-1) p.o.). At the end of the experiments, Pb, Ca and Zn in the carcass and Pb, Fe and Cu in the liver, kidneys and brain were analysed by atomic absorption spectrometry. Calcium supplementation during lead exposure reduced tissue lead but had no effect when applied after lead exposure, and DMSA administered either during or after lead exposure lowered the tissue lead. Combined treatment during ongoing lead exposure caused a greater reduction in tissue lead than either DMSA or calcium treatment alone. When administered after lead exposure, it had no advantage over DMSA treatment alone but did not impair its efficacy. Combined treatment had no influence on growth and did not seriously disturb essential element status. It is concluded that calcium supplementation could be applied during DMSA therapy, when indicated.
在两种实验条件下,评估了内消旋 - 2,3 - 二巯基丁二酸(DMSA)与补钙联合治疗对降低乳鼠铅吸收及增强铅排出的作用:一是在持续口服铅暴露期间(醋酸铅,2 mg Pb kg⁻¹ 天⁻¹,总剂量16 mg Pb kg⁻¹),二是在铅暴露后(2天铅暴露后72小时,总剂量12 mg Pb kg⁻¹ 皮下注射)。采用人工喂养法补钙,用牛奶中6% Ca(以CaHPO₄形式)悬浮液使每日钙摄入量比对照值增加约三倍。人工喂养连续八天,每天持续7小时。在此期间,DMSA在6天内每天给药两次(0.5 mmol kg⁻¹ 天⁻¹ 口服)。实验结束时,通过原子吸收光谱法分析 carcass 中的Pb、Ca和Zn以及肝脏、肾脏和大脑中的Pb、Fe和Cu。铅暴露期间补钙可降低组织铅含量,但在铅暴露后应用则无作用,而在铅暴露期间或之后给予DMSA均可降低组织铅含量。在持续铅暴露期间联合治疗导致组织铅含量降低的幅度大于单独使用DMSA或钙治疗。在铅暴露后给药时,它与单独使用DMSA治疗相比没有优势,但也不损害其疗效。联合治疗对生长没有影响,也不会严重干扰必需元素状态。结论是,在有指征时,补钙可在DMSA治疗期间应用。