Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys.

Cremin, J. D.; Luck, Melissa L.; Laughlin, Nellie K.; Smith, Donald R.

doi:10.1289/ehp.01109613

Cited by 16 publications

(6 citation statements)

References 47 publications

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“…Results are presented as arithmetic means ± SEM, with 10 animals in each group; significant comparisons: * DMSA vs untreated (by F-test; P < 0.05); b One brain sample in the DMSA group and two brain samples in the DMSA + Ca group were lost during preparation. Pb isotope and also enhanced lead elimination (Cremin et al, 2001). Studies in rodents in the post-weaning period also confirmed the efficacy of DMSA under conditions of concomitant lead exposure (Kapoor et al, 1989;Pappas et al, 1995;Gong & Evans, 1997).…”

Section: Discussionmentioning

confidence: 77%

“…Concerning treatment with DMSA, our results indicate that DMSA is effective when administered either during or after lead exposure. A recent study on juvenile monkeys showed the DMSA therapy during ongoing oral lead exposure significantly decreased the gastrointestinal absorption of the stable 206 Pb isotope and also enhanced lead elimination (Cremin et al, 2001). Studies in rodents in the post-weaning period also confirmed the efficacy of DMSA under conditions of concomitant lead exposure (Kapoor et al, 1989;Pappas et al, 1995;Gong & Evans, 1997).…”

Section: Discussionmentioning

confidence: 91%

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Succimer treatment and calcium supplementation reduce tissue lead in suckling rats

Varnai¹,

Piasek²,

Blanuša³

et al. 2004

J of Applied Toxicology

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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.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 91%

Succimer treatment and calcium supplementation reduce tissue lead in suckling rats

Varnai¹,

Piasek²,

Blanuša³

et al. 2004

J of Applied Toxicology

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“…*Succimer group differs from the vehicle group according to an ANOVA (p <0.05). Data from Cremin et al [12].…”

Section: Is Brain Lead Reduced With Chelation and Do Reductions In Bmentioning

confidence: 99%

“…We also evaluated fecal lead elimination with chelation, using complete 24-h fecal samples collected over the first 5 days of treatment [12]. These data are summarized in Fig.…”

Section: Introductionmentioning

confidence: 99%

The Scientific Basis for Chelation: Animal Studies and Lead Chelation

Smith

Strupp

2013

J. Med. Toxicol.

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This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal-chelating agents to children who do not have elevated tissue lead levels. It is of significant concern that this type of therapy has been advocated for treating autism.

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“…Biliary lead excretion has been shown to range between 40 and 85% of total body lead excretion in nonhuman primates (Cremin et al 2001; O’Flaherty et al 1996) and < 46% in adult humans (Rabinowitz et al 1976), and it is estimated to be at least 50% in infants (Ziegler et al 1978). Assuming that the lead isotopic composition of bile matches that of blood, the biliary elimination of endogenous lead into feces would shift the lead isotopic value of feces toward the isotopic value of blood, although the extent of this shift would depend on the amount (e.g., micrograms) of lead eliminated from this biliary route compared with the amount of lead in the feces (i.e., unabsorbed lead from oral intake).…”

Section: Discussionmentioning

confidence: 99%

A Noninvasive Isotopic Approach to Estimate the Bone Lead Contribution to Blood in Children: Implications for Assessing the Efficacy of Lead Abatement

Gwiazda

Campbell

Smith

2005

Environ Health Perspect

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Lead hazard control measures to reduce children’s exposure to household lead sources often result in only limited reductions in blood lead levels. This may be due to incomplete remediation of lead sources and/or to the remobilization of lead stores from bone, which may act as an endogenous lead source that buffers reductions in blood lead levels. Here we present a noninvasive isotopic approach to estimate the magnitude of the bone lead contribution to blood in children following household lead remediation. In this approach, lead isotopic ratios of a child’s blood and 5-day fecal samples are determined before and after a household intervention aimed at reducing the child’s lead intake. The bone lead contribution to blood is estimated from a system of mass balance equations of lead concentrations and isotopic compositions in blood at the different times of sample collection. The utility of this method is illustrated with three cases of children with blood lead levels in the range of 18–29 μg/dL. In all three cases, the release of lead from bone supported a substantial fraction of the measured blood lead level postintervention, up to 96% in one case. In general, the lead isotopic compositions of feces matched or were within the range of the lead isotopic compositions of the household dusts with lead loadings exceeding U.S. Environmental Protection Agency action levels. This isotopic agreement underscores the utility of lead isotopic measurements of feces to identify household sources of lead exposure. Results from this limited number of cases support the hypothesis that the release of bone lead into blood may substantially buffer the decrease in blood lead levels expected from the reduction in lead intake.

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Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys.

Cited by 16 publications

References 47 publications

Succimer treatment and calcium supplementation reduce tissue lead in suckling rats

Succimer treatment and calcium supplementation reduce tissue lead in suckling rats

The Scientific Basis for Chelation: Animal Studies and Lead Chelation

A Noninvasive Isotopic Approach to Estimate the Bone Lead Contribution to Blood in Children: Implications for Assessing the Efficacy of Lead Abatement

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