Efficacy of Succimer Chelation for Reducing Brain Lead in a Primate Model of Human Lead Exposure

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

doi:10.1006/taap.1999.8807

Cited by 42 publications

(34 citation statements)

References 42 publications

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“…The significant reductions in total BPb levels over the first 8 days of succimer treatment are consistent with the larger data set containing these animals (n = 22-24/treatment) that showed significant reductions in BPb level over both the first and second chelation regimens (17). These data are also consistent with studies in adult monkeys (37) and studies in children (1,25). Our observation that total BPb levels in the vehicle group did not measurably decline over the study period may simply be attributed to the fact that oral Pb exposure to these animals had ceased at 52 weeks of age, 12 weeks before the present study.…”

Section: Discussionsupporting

confidence: 87%

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

Cremin

Luck

Laughlin

et al. 2001

Environ Health Perspect

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Although succimer (Chemet, meso-2,3-dimercaptosuccinic acid, DMSA) is considered to be a safe and effective chelating agent for the treatment of lead poisoning in humans, there is concern that it may increase the gastrointestinal (GI) absorption and retention of Pb from exposures suffered concurrent with treatment. This concern is justified because the availability of Pb-safe housing during outpatient treatment with oral succimer is limited. We used a juvenile nonhuman primate model of moderate childhood Pb intoxication and a sensitive double stable Pb isotope tracer methodology to determine whether oral succimer chelation affects the GI absorption and whole-body retention of Pb. Infant rhesus monkeys (n = 17) were exposed to Pb daily for 1 year postpartum to reach and maintain a target blood lead (BPb) level of 35-40 microg/dL. Animals were administered succimer (n = 9) or vehicle (n = 8) over two successive 19 day succimer treatment regimens beginning at 53 and 65 weeks of age. The present study was conducted over the second chelation regimen only. Animals received a single intravenous (iv) dose of stable (204)Pb tracer (5 microg, 24.5 nmol) followed by a single oral dose of stable (206)Pb tracer (72.6 microg, 352 nmol) immediately before chelation, in order to specifically evaluate GI Pb absorption and whole-body Pb retention with treatment. We collected complete urine and fecal samples over the first 5 days and whole blood over the first 8 days of treatment for analyses of stable Pb isotopes using magnetic sector inductively-coupled plasma mass spectrometry. Results indicate that succimer significantly reduced the GI absorption of Pb (vehicle, 64.9% +/- 5.5; succimer, 37.0% +/- 5.8; mean +/- SEM). Succimer also significantly increased the urinary excretion of endogenous Pb by approximately 4-fold over the vehicle treatment, while endogenous fecal Pb excretion was decreased by approximately 33%. Finally, although succimer reduced the whole-body retention of endogenous Pb by approximately 10% compared to vehicle, the majority (77%) of the administered internal dose of Pb tracer was retained in the body when assessed after 5 days of treatment. These data do not support the concern that succimer treatment increases GI Pb absorption.

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Section: Discussionsupporting

confidence: 87%

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

Cremin

Luck

Laughlin

et al. 2001

Environ Health Perspect

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“…We will present results from the primate study first [13]. The study design allowed for five to six animals each per control and succimer treatment group.…”

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

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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“…These metals are potentially toxic to crops, because they accumulate fast in the vital organ of crops grown in metals contaminated site, thus animal and human that consume such crops are at great danger of heavy metals toxicity (Whang et al, 2008). Iron like cobalt, copper, chromium, manganese and nickel are required in trace amount by plant and human but excessive intake results in a disease condition called Hemochromatosis, inability of the intestine to keep out unneeded iron in the intestine in human and perhaps negatively affect soil microbial diversity (Cremin et al, 2004). Recently, an increase concern about environmental protection has caused the development of cost effective and environmental friendly microbial compounds that exhibit pronounced surface and emulsifying activities called biosurfactant (Morita et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Remediation of Iron Using Rhamnolipid-Surfactant Produced by Pseudomonas aeruginosa

Akintunde¹,

Abioye²,

Oyeleke³

et al. 2015

Research J. of Environmental Sciences

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Pseudomonas aeruginosa was isolated from 20 years abandoned mine site of Itagunmodi Atakunmosa West, Ilesha, Nigeria. Atomic absorption Spectrophotometry (AAS) revealed Fe, Mn, Cr, Zn, Pb and Cr, while, Fe has the highest concentration range of 29-289 ppm in the analysed soil samples. Soil samples were enriched in R2b agar, serially diluted and pour plated. Four bacteria strains were isolated and identified using standard biochemical test. After routine biosurfactant screening by oil spreading and emulsification test, biosurfactant producing bacteria was confirmed as Pseudomonas aeruginosa. The partially purified biosurfactants were characterized with TLC and GC-MS analysis. The analyses indicated glycolipid biosurfactant specifically designated as Rhamnolipid-sa1 containing isopalmitic acid, hexadecanoic acid, methyl ester and hydroxylated fatty acid linked to decanoic acids. Iron removal potential of the extracted biosurfactant was studied and the result revealed that Rhamnolipid-sa1 effectively reduced iron (60.34%) and could be useful as alternative remediation tool for treatment of iron contaminated soil.

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Efficacy of Succimer Chelation for Reducing Brain Lead in a Primate Model of Human Lead Exposure

Cited by 42 publications

References 42 publications

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

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

The Scientific Basis for Chelation: Animal Studies and Lead Chelation

Remediation of Iron Using Rhamnolipid-Surfactant Produced by Pseudomonas aeruginosa

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