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Background Lead (Pb) exposure impairs cognitive functions of children. Whether Pb exposure in different developmental stages induces long-term cognitive impairment, and whether chelation therapy could mitigate the cognitive impairment is rarely reported. Objective This experiment is designed to investigate effects of Pb exposure and chelation therapy during different developmental stages (breastfeeding, weaning, and early puberty periods) on mouse short-term and long-term cognitive functions. Methods C57BL/6 male mice in breastfeeding period, weaning period, and early puberty period (postnatal day 2, 21, and 41; PND 2, PND 21, and PND 41, n=30, respectively) were randomly divided into control, Pb exposure, and Pb+dimercaptosuccinic acid (DMSA) treatment groups (n=10 in each group). The control groups received standard food and deionized water. The Pb exposure mice received standard food and free drinking water containing Pb acetate (0.1% for dams, and 0.05% for pups). After receiving Pb acetate for 19 d, the Pb+DMSA treatment groups were given 1 mmol·kg−1·d−1 DMSA for 6 d with gastric infusion. Whole blood Pb levels were measured after DMSA treatment on experimental day 25. The effects on short-term cognitive function were tested in the Morris Water Maze task by the analyses of escape latency on PND 75−79, as well as target quadrant time and times of platform-crossing on PND 80. Hippocampal long-term potentiation of field excitatory postsynaptic potential (fEPSP) of mice on PND 365 was induced to demonstrate the effects on long-term cognitive function. Results The blood Pb levels among the Pb, Pb+DMSA, and control groups were statistically different for each developmental stage (Fbreastfeeding period=43.47, Fweaning period=228.6, Fearly period of puberty=274.2, all P<0.001). Compared to the counterpart control groups, blood Pb levels of the pb exposure groups (386.4, 265.0, and 178.1 μg·L−1 in breastfeeding period, weaning period, and early puberty period, respectively) were significantly higher for all stages. After the chelation therapy, the blood Pb significantly decreased for all stages (28.68, 47.29, and 20.93 μg·L−1 in the three periods, respectively, all P<0.001) and the Pb levels of the mice exposed in the breastfeeding period decreased most (by 92.58%, 82.15%, and 88.25% in the three periods, respectively, P<0.01). In the water maze task, the mice exposed to Pb in the breastfeeding period had a gentler decrease in escape latency (from 54.20 s on day 1 to 30.54 s on day 5, by 43.65 % decrease) than the control group (from 32.44 s on day 1 to 15.20 s on day 5, by 53.14 % decrease) (P<0.01) and a significant decrease in target quadrant time (P<0.05). After the chelation therapy, the escape latency of the DMSA-treated mice in the breastfeeding period (from 40.94 s on day 1 to 20.87 s on day 5, by 48.99 % decrease) was steeper than that of the Pb-exposed mice (P<0.05). The differences in the escape latency, target quadrant time, and times of platform-crossing were not significant between the Pb-exposed mice and the control mice in the weaning period and early period of puberty (all P>0.05). After the chelation therapy, such differences were also not significant compared with before therapy. Due to the small sample size, data were merged for different developmental stages in the long-term potentiation test. The amplitudes of fEPSP induced in the control, Pb-exposed, and DMSA treatment groups were significantly different (Fgroups=212.2, Ftime=11.36. P<0.001). The average fEPSP amplitude induced in the last 10 min recorded in the hippocampal slices in the Pb exposure group was significantly lower than that in the control group (P<0.05). After the DMSA treatment, no significant differences were observed in the fEPSP amplitudes between the Pb exposure group and the DMSA treatment group (P>0.05). When observing the fEPSP data by developmental stages, the fEPSP amplitude in the breastfeeding Pb-exposure group was 27.2% lower than that of the breastfeeding control group, while such changes were not obvious in the weaning period or in the early period of puberty. The fEPSP amplitude in breastfeeding DMSA treatment group was 44.3% higher than that of the breastfeeding Pb exposure group, while such changes were not observed in the weaning period or in early period of puberty. Conclusion Pb exposure during different developmental stages, especially in breastfeeding period, could affect short-term and long-term cognitive functions of mice. The harmful effects may be partially reversed by DMSA chelation therapy, especially being treated in breastfeeding period.
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Objectives To explore the efficacy of CaNa2EDTA in the treatment of chronic moderate lead poisoning, so as to optimize the chelation therapy for lead poisoning in children. Methods The clinical data of 14 patients with chronic moderate lead poisoning treated with CaNa2EDTA for 3 consecutive courses of lead removal during September 2014 to December 2016 were analyzed retrospectively. Twenty-four hour urinary lead levels during hospitalization were analyzed. The changes of blood lead levels before treatment, 3 days, and 5 days after treatment were also analyzed. Results In the 14 children (4 males and 10 females) average age was 2.35±1.47 years. After treatment with CaNa2EDTA for 3 consecutive courses, the blood lead levels were decreased significantly in all the patients, and the blood lead levels at 3 days after treatment were 0.76, 0.77, 0.72 times those at 5 days after treatment respectively. The decrease of blood lead levels per unit of drug in the first 3 days of treatment were significantly higher than those in 5 days of treatment (P<0.05). The decrease of blood lead levels at 3 days after treatment was 0.65, 0.71, 0.70 times , those in 5 days' treatment respectively. The decrease of urine lead levels per unit of drug in the first 3 days of treatment were significantly higher than those in 5 days of treatment (P<0.05). Conclusions CaNa2EDTA has an obvious effect on removal of lead.The efficiency of lead removal in 3 days of treatment was higher than in 5 days of treatment. Thus, a course of treatment for 3 days may be an altenative for a course of 5 days.
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Lead poisoning has become a big threat to public health in China. Traditional treatments usually use chelators to accelerate the excretion of lead by forming complex compounds with it. However, chelators exhibit side effects and have little therapeutic effect on lead-induced impairment so that better drugs are needed. As antioxidants are effective for the treatment of lead poisoning, with lasting effect and little side effect, they have been the focus of increasing studies. This review provides a detailed account of updates on the effects of antioxidant drugs in the therapy of lead poisoning, and of the progress in antioxidant activity of puerarin, quercetin, curcumin, allicin and melatonin in treatment of lead poisoning. To some extent, these five types of drugs can reduce lead poisoning by accelerating lead excretion and antioxidant, increase the body′s antioxidant enzyme activity, reduce oxidative stress and repair damage, which promises some clinical value.