succimer and Lead-Poisoning

Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical practice in this area is rather scattered.. We present a case of symptomatic lead and arsenic poisoning from use of Ayurvedic medicine in a 28-year-old man with end-stage kidney disease on chronic hemodialysis. We describe his treatment course with chelating agents and extracorporeal blood purification, and review the relevant literature to provide general guidance.. Cumulative clinical experience assists in identifying preferred chelators and modalities of extracorporeal blood purification when managing such patients. However, a larger body of real-world or clinical trial evidence is necessary to inform evidence-based guidelines for the management of heavy metal poisoning in anuric patients.

Topics: Adult; Animals; Anuria; Arsenic Poisoning; Chelating Agents; Continuous Renal Replacement Therapy; Dimercaprol; Edetic Acid; Humans; Kidney Failure, Chronic; Lead Poisoning; Male; Renal Dialysis; Succimer; Unithiol

In the present review we provide an update of the appropriate use of chelating agents in the treatment of intoxications with compounds of mercury, lead and copper. The relatively new chelators meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-propanesulphonate (DMPS) can effectively mobilize deposits of mercury as well as of lead into the urine. These drugs can be administered orally and have relatively low toxicity compared to the classical antidote dimercaptopropanol (BAL). d-Penicillamine has been widely used in copper overload, although 2,3-dimercaptosuccinic acid or tetrathiomolybdate may be more suitable alternatives today. In copper-toxicity, a free radical scavenger might be recommended as adjuvant to the chelator therapy.

Topics: Administration, Oral; Animals; Chelating Agents; Chelation Therapy; Copper; Drug Therapy, Combination; Evidence-Based Medicine; Free Radical Scavengers; Humans; Infusions, Parenteral; Lead Poisoning; Mercury Poisoning; Penicillamine; Succimer; Trientine; Unithiol

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.

Topics: Animals; Behavior, Animal; Body Burden; Brain; Chelating Agents; Chelation Therapy; Disease Models, Animal; Humans; Lead; Lead Poisoning; Risk Assessment; Risk Factors; Succimer; Time Factors; Treatment Outcome

This article reviews data on the efficacy of succimer (dimercaptosuccinic acid, DMSA) in the treatment of human inorganic lead poisoning, the adverse effects associated with its use, and summarizes current understanding of the pharmacokinetic and pharmacodynamic aspects.. Medline, Toxline, and Embase were searched and 912 papers were identified and considered. PHARMACOKINETICS AND PHARMACODYNAMICS: DMSA is absorbed rapidly but incompletely after oral administration, probably through an active transporter. There is evidence that enterohepatic circulation occurs. Most DMSA in plasma is protein (mainly albumin)-bound through a disulfide bond with cysteine; only a very small amount is present as free drug, which is filtered at the glomerulus then extensively reabsorbed into proximal tubule cells. Nonfiltered protein-bound DMSA in peritubular capillaries is also available for uptake into proximal tubule cells by active anion transport at the basolateral membrane. DMSA therefore accumulates in the kidney where it is extensively metabolized in humans to mixed disulfides of cysteine. Some 10-25% of an orally administered dose of DMSA is excreted in urine, the majority within 24 h and most (>90%) as DMSA-cysteine disulfide conjugates. It is not known whether protein-bound DMSA can chelate lead; there is evidence that the mixed disulfides of cysteine are the active chelating moiety in humans. If this is the case, this suggests that chelation occurs principally, if not exclusively, in the kidney. DOSE: DMSA 30 mg/kg/day is more effective than either 10 or 20 mg/kg/day in enhancing urine lead excretion. DURATION OF THERAPY: Initial clinical studies with DMSA involved the administration of a 5-day course of treatment. Subsequently, a 19- to 26-day regimen was introduced with the intent of preventing or at least blunting a rebound in the blood lead concentration. Studies suggest, however, that repeated courses of DMSA 30 mg/kg/day for at least 5 days are equally efficacious if a treatment-free period of at least 1 week between courses is included to allow redistribution of lead from bone to soft tissues and blood. There is also evidence that in more severely poisoned patients DMSA 30 mg/kg/day can be given for more than 5 days with benefit.. DMSA 30 mg/kg/day significantly increases urine lead elimination and significantly reduces blood lead concentrations in lead-poisoned patients, though there is substantial individual variation in response. Over a 5-day course, mean daily urine lead excretion exceeds baseline by between 5- and 20-fold and blood lead concentrations fall to 50% or less of the pretreatment concentration, with wide variation. Maximum enhancement of urine lead elimination typically occurs with the first dose. Most symptomatic patients report improvement after 2 days of treatment. However, DMSA did not improve cognition in children < 3 years old with mild lead poisoning, presumably because lead-induced neurological damage occurred during development in utero and/or early infancy. DMSA IN PREGNANCY AND IN THE NEONATE: DMSA is not teratogenic but did produce maternal toxicity (decreased weight gain) and fetotoxicity when given in high dose (100-1,000 mg/kg/day) in experimental studies. For this reason sodium calcium edetate is generally preferred in pregnancy.. A transient modest rise in transaminase activity during chelation occurs in up to 60% of patients but has not resulted in clinically significant sequelae. Skin reactions occur in approximately 6% of treated patients and are occasionally severe. DMSA also increases urine copper and zinc excretion but not to a clinically important extent.. DMSA is an effective lead chelator that primarily chelates renal lead. It is generally well tolerated but may occasionally cause clinically important adverse effects. DMSA may now be considered as an alternative to sodium calcium edetate, particularly when an oral antidote is preferable.

Topics: Adult; Animals; Antidotes; Chelating Agents; Child; Databases, Bibliographic; Female; Humans; Infant, Newborn; Kidney; Lead Poisoning; Pregnancy; Protein Binding; Succimer; Young Adult

This article reviews the experimental and clinical studies that have compared the efficacy (impact on urine lead excretion, blood and tissue lead concentrations, resolution of features and survival) of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. It also summarizes the pharmacokinetic and pharmacodynamic aspects and the adverse effects of treatment.. Medline, Toxline, and Embase were searched for all available years to June 2009. PHARMACOKINETICS AND PHARMACODYNAMICS: The absorption of oral DMSA is more complete than sodium calcium edetate; the latter has to be administered parenterally. Both antidotes are distributed predominantly extracellularly. Sodium calcium edetate is not metabolized, whereas DMSA is extensively metabolized to mixed disulfides of cysteine. The two antidotes have elimination half-lives of less than 60 min. There is no evidence that either antidote crosses the blood-brain barrier to any major extent. Sodium calcium edetate chelates lead by displacement of the central Ca2+ ion with Pb2+. The nature of the DMSA-lead chelate is less clearly defined. There is evidence that the mixed disulfides of cysteine are the active chelating moiety in humans. If this is the case, this suggests that chelation occurs principally, if not exclusively, in the kidney. The primary source of lead mobilized by sodium calcium edetate is bone with an additional contribution from kidney and liver.. Comparison of the experimental studies is complicated by substantial variations in study design, particularly the antidote dose, the route and duration of treatment, the amount and duration of lead dosing, and lack of direct comparison between antidotes (comparison was usually made with control). In experimental studies that used equimolar and clinically relevant antidote doses and assessed the impact of DMSA and sodium calcium edetate on urine lead excretion and/or blood lead concentrations, similar results were found, though no direct comparison between antidotes was undertaken. DMSA was more effective than sodium calcium edetate in reducing the kidney lead concentration, sodium calcium edetate was more effective than DMSA in reducing bone lead concentrations, and there was no consistently observed effect of chelation therapy on brain lead concentrations in these experimental studies. Only two clinical studies have compared equimolar or similar antidote doses in enhancing urine lead excretion; there was no statistical difference between the antidotes, though both studies had limitations. DMSA and sodium calcium edetate had a comparable impact on lowering blood lead concentrations in a clinical study using similar molar antidote doses.. Sodium calcium edetate causes dose-related nephrotoxicity. Both agents deplete zinc and copper, the effect on zinc being significantly greater with sodium calcium edetate. A transient increase in hepatic transaminase activity has been reported with both antidotes but appears to be more common with DMSA and neither has been associated with clinically significant hepatic toxicity. Skin lesions during treatment with sodium calcium edetate are unusual and have been attributed to zinc deficiency. DMSA has occasionally been associated with a severe mucocutaneous reaction necessitating discontinuation of therapy.. Oral DMSA and parenteral sodium calcium edetate are both effective chelators of lead. There are currently insufficient data, however, to conclude that either antidote is superior in enhancing lead excretion. Both antidotes resolve the symptoms of moderate and severe lead toxicity rapidly. Although there is greater clinical experience with sodium calcium edetate, particularly in the treatment of lead encephalopathy, oral DMSA may now be considered as an alternative in circumstances where oral therapy is preferable.

Topics: Administration, Oral; Animals; Antidotes; Chelating Agents; Clinical Trials as Topic; Edetic Acid; Humans; Lead; Lead Poisoning; Succimer

Health hazards caused by heavy metals have become a great concern to the population. Lead and arsenic are one of the most important current global environmental toxicants. Their toxic manifestations are being considered caused primarily due to the imbalance between pro-oxidant and antioxidant homeostasis and also due to a high affinity of these metals for thiol groups on functional proteins. They also interfere with a number of other body functions and are known to affect central nervous system (CNS), hematopoietic system, liver and kidneys and produce serious disorders. They produce both acute and chronic poisoning, of which chronic poisoning is more dangerous as its very difficult to revert back to normal condition after chronic exposure to these insidious metals present in our life. Despite many years of research, we are still far from an effective treatment of chronic plumbism and arsenicosis. Current approved treatment lies in the administration of chelating agents that forms an insoluble complex with the metal and removes it. They have been used clinically as antidotes for treating acute and chronic poisoning. The most widely used chelating agents are calcium disodium ethylenediamine tetra acetic acid (CaNa2EDTA), D-penicillamine and British anti-lewisite (BAL). Meso 2,3 dimercaptosuccinic acid (DMSA), an analogue of BAL, has been tried successfully in animals as well as in humans. But it is unable to remove the metal from intracellular sites. Effective chelation therapy for intoxication by heavy metals depends on whether the chelating agents are able to reach the intracellular site where the heavy metal is firmly bound. One of the important approaches has been the use of combination therapy. This includes use of structurally different chelators or a combination of an adjuvant/ antioxidant/ herbal extracts and a chelator to provide better clinical/ biochemical recovery. A number of other strategies have been suggested to minimize the numerous problems. This article presents the recent development made in this area with possible directions for future research.

Topics: Acetylcysteine; Adjuvants, Pharmaceutic; Animals; Antioxidants; Arsenic; Arsenic Poisoning; Ascorbic Acid; Calcium; Chelating Agents; Free Radicals; Humans; Lead; Lead Poisoning; Melatonin; Metals; Micronutrients; Molecular Structure; Succimer; Taurine; Thioctic Acid; Unithiol; Vitamin E

Topics: Child; Edetic Acid; Environmental Pollution; Health Education; Humans; Lead Poisoning; Penicillamine; Succimer

Although the incidence of lead toxicosis in small animals continues to decrease, it remains a significant malady. We have reviewed the literature of the past 45 years, which revealed 70 cases involving cats. Sources, signs, diagnosis, pathology and treatment of feline lead toxicosis are reviewed. In 84% of these cases the source of lead was old paint usually from home renovation. The most common signs in cats are anorexia, vomiting, and seizures. The younger individuals seem more likely to show CNS signs. Since signs are often vague, lead toxicosis may be significantly under diagnosed in cats. The gold standard of diagnostic tests is blood lead concentration, although it does not necessarily correlate with total body burden of lead or with metabolic effects including clinical signs. Diagnostic tests including erythropoietic protoporphyrin (EPP), urine aminolevulinic acid, and others are discussed. Gross findings on necropsy are few and include a yellow-brown discoloration of the liver often with a nutmeg-like appearance. Histological examination may reveal pathognomonic inclusion bodies in liver and renal tissues. Characteristic histological changes in the CNS include neuronal necrosis and demyelination. Treatment of lead toxicosis in cats, as in any species, involves removing the exposure, decontaminating the individual and the environment, supportive care and chelation therapy. The most recently available chelator is succimer (meso 2,3-dimercaptosuccinic acid). Succimer given orally is well tolerated and has a wide margin of safety. A high index of suspicion of lead toxicosis is warranted in cats since they often present with vague and non-specific signs. With any consistent history owners need to be asked about home renovation. Early diagnosis and treatment affords a good prognosis.

Topics: Animals; Anorexia; Cat Diseases; Cathartics; Cats; Chelating Agents; Lead Poisoning; Seizures; Succimer; Vomiting

Topics: Chelating Agents; Chelation Therapy; Child; Child Development; Child, Preschool; Cognition Disorders; Environmental Exposure; Humans; Lead; Lead Poisoning; Randomized Controlled Trials as Topic; Succimer; Treatment Outcome

Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.

Topics: Arsenic Poisoning; Cadmium Poisoning; Chelating Agents; Heavy Metal Poisoning; Humans; Lead Poisoning; Mercury Poisoning; Poisoning; Succimer

To report a case of a 3-year-old child with an extraordinarily massive lead concentration, 26.4 micromol/L (550 microg/dL), following environmental exposure to lead paint in the home.. The relevant literature concerning the treatment of lead encephalopathy was reviewed during the treatment of this child and preparation of the manuscript. To our knowledge, the landmark article written by Julian Chisolm in 1968 is the only recent article that reported similarly high levels of lead concentration. This case, however, is the first in which 3 chelating agents were used for the treatment of lead encephalopathy. We also reviewed the literature on the use of whole bowel irrigation in heavy metal intoxications.. In this case, aggressive gut decontamination with whole bowel irrigation and triple chelation therapy with British anti-Lewisite, EDTA, and oral succimer was well tolerated and seemed effective for rapidly deleading the child. The extent to which her lead concentration increased while being treated with oral succimer alone necessitated further chelation with EDTA. Further evaluation is necessary to determine if triple chelation therapy is an appropriate method for severe lead intoxication, and if the use of whole bowel irrigation should be considered in heavy metal intoxication.

Topics: Brain Diseases; Child, Preschool; Dimercaprol; Edetic Acid; Environmental Exposure; Female; Humans; Iron Chelating Agents; Lead; Lead Poisoning; Paint; Polyethylene Glycols; Succimer; Therapeutic Irrigation

Increased lead exposure and increased body burden of lead remains a significant problem for children in the United States. With the increased use of blood level screening methods, a large percentage of children in many industrialized countries are being tested as a being at risk. A controversy continues over the definition of what population to screen and at what age to screen. There are parts of the United States, especially rural areas and health maintenance organization populations, where screening for lead exposure has not been productive. A new drug, DMSA (meso 2,3-dimercaptosuccinic acid) has been approved for oral chelation of children with increased body burden of lead. At the present time it is labeled for use in children with blood lead concentrations in excess of 45 micrograms/dL. Evidence exists that DMSA is effective in lowering the blood lead concentrations in children with levels between 25 and 45 micrograms/dL. The long-term effectiveness of chelation at lower levels is at present uncertain. There remains no substitution for strict environmental decontamination in the home environment of children and the workplace environment of their parents.

Topics: Chelating Agents; Child; Humans; Lead Poisoning; Succimer

Topics: Dental Amalgam; Humans; Lead Poisoning; Mercury Poisoning; Succimer; Unithiol; Volatilization

Topics: Administration, Oral; Chelation Therapy; Child; Drug Monitoring; Humans; Lead Poisoning; Penicillamine; Succimer

The Centers for Disease Control and Prevention has redefined the threshold of concern for low-level lead toxicity, reducing it from a blood lead level of 25 micrograms per dL (1.21 mumol per L) to a blood lead level of 10 micrograms per dL (0.48 mumol per L), and has recommended universal screening of young children. Succimer (2,3-dimercaptosuccinic acid) is an effective oral lead chelating agent that has been approved for outpatient treatment of children with blood lead levels higher than 45 micrograms per dL (2.17 mumol per L). In the United States, clinical experience with succimer is limited; however, observed side effects, including gastrointestinal symptoms, rash and transient elevations of serum aminotransferase levels, are uncommon and mild. Isolated cases of neutropenia have been reported. Weekly monitoring of complete blood counts and serum aminotransferase levels is recommended during the 19-day treatment. Blood lead levels should be checked weekly to identify rebound from bone and soft tissue mobilization.

Topics: Administration, Oral; Ambulatory Care; Clinical Trials as Topic; Drug Costs; Drug Eruptions; Drug Monitoring; Edetic Acid; Female; Gastrointestinal Diseases; Humans; Lead Poisoning; Mass Screening; Metabolic Clearance Rate; Neutropenia; Pregnancy; Succimer; Transaminases; United States; United States Food and Drug Administration

Topics: Chelation Therapy; Child; Dimercaprol; Edetic Acid; Humans; Lead; Lead Poisoning; Penicillamine; Succimer

2,3-Dimercaptosuccinic acid (DMSA) is an orally active chelating agent used in the treatment of lead and other heavy metal poisonings. In animals, DMSA chelates lead from soft tissues, including the brain, without clinically evident adverse effects or histopathological changes. In lead-poisoned children and adults, DMSA significantly increases urinary lead excretion, and, at least transiently, reduces the blood lead concentration. The safety profile of DMSA in both children and adults is encouraging, with few clinically apparent or biochemical adverse effects reported. However, clinical experience with DMSA is limited, and is not sufficient to exclude the possibility that other more serious drug-related adverse events including hypersensitivity or idiosyncratic reactions may occur. No data currently exist to determine whether drug-enhanced lead excretion with DMSA (or any other chelating agent) is beneficial in reducing lead-related neurotoxicity. The efficacy of DMSA in reducing neuropsychological morbidity, and additional safety data, are key areas requiring additional study before DMSA can be clearly recommended as the chelating agent of choice for the treatment of lead-poisoned children.

Topics: Administration, Oral; Adult; Animals; Chelating Agents; Child; Child, Preschool; Humans; Lead Poisoning; Succimer

Topics: Animals; Arsenic Poisoning; Chelating Agents; Chelation Therapy; Dimercaprol; Edetic Acid; Humans; Lead Poisoning; Mercury Poisoning; Poisoning; Succimer

The most recent Centers for Disease Control guidelines recommend routine screening of children for lead exposure. The CDC recommends close lead-level monitoring of children with lead levels greater than 10 micrograms/dL. The indications for chelation therapy have not changed. Identification and removal of sources of lead exposure are equally as important as chelation therapy. Experimental data have raised concerns about potential central nervous system effects of the most widely used chelating agent, edetate calcium disodium. A newly licensed chelating agent, succimer, appears to have fewer side effects, appears to be more effective, and has the advantage of oral administration. Indications for its use are somewhat limited but may be expanded as experience with its use increases.

Topics: Chelation Therapy; Child; Humans; Lead; Lead Poisoning; Succimer

Topics: Charcoal; Child; Child, Preschool; Cocaine; Female; Gastric Lavage; Gastrointestinal Diseases; Humans; Infant; Ipecac; Lead Poisoning; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; Risk Factors; Succimer; Toxicology

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of succimer when used for the treatment of lead poisoning are reviewed. Succimer is an orally active, heavy-metal chelating agent that forms stable, water-soluble complexes with lead; it also chelates other toxic heavy metals, such as arsenic and mercury. It is a designated orphan drug that is indicated for the treatment of lead poisoning, specifically in children with blood lead concentrations higher than 45 micrograms/dL. Succimer reverses the adverse metabolic effects of lead on heme synthesis while increasing urinary lead output without adversely affecting essential mineral excretion at the recommended dosage regimen. The rebound in lead concentrations that can occur after short courses of chelating therapies (caused by redistribution of lead from bone stores) may require frequent and multiple courses of chelation therapy. The most common adverse effects reported in clinical trials of succimer in children and adults were nausea, vomiting, diarrhea, appetite loss, and loose stools; these effects may be related to the drug's unpleasant mercaptan odor. There are no known drug interactions between succimer and other drugs, including iron supplements, although data are limited. The recommended initial dosage in children is 10 mg/kg or 350 mg/sq m every eight hours for five days. The dosage is then reduced to 10 mg/kg or 350 mg/sq m every 12 hours for an additional two weeks. Clinical studies indicate that succimer is relatively selective for lead and effectively lowers blood lead concentrations. Although clinical experience is limited, an oral lead chelator may offer advantages over currently available agents.

Topics: Administration, Oral; Chelation Therapy; Drug Interactions; Drug Monitoring; Drug Stability; Humans; Lead; Lead Poisoning; Succimer

In the overall long-term management of lead poisoning, chelation therapy can have short-term benefits; however, these benefits must be accompanied by drastic reduction in environmental exposure to lead if therapy is to have any long-term benefit. This discussion is limited to calcium disodium ethylenediaminetetraacetate (CaNa2EDTA), the chelating agent that has been the mainstay of treatment of lead poisoning for the past 38 years, and to meso-2,3-dimercaptosuccinic acid (DMSA), a new and promising oral chelating agent, which is an orphan drug and is currently classified as an investigational new drug by the U.S. Food and Drug Administration. With both drugs, multiple courses of treatment will be needed if any substantial reduction in body lead burden is to be achieved. A major limitation of CaNa2EDTA is the enormous diuresis of zinc that it produces. DMSA produces a comparable diuresis of lead, a greater decrease in blood lead, and has negligible influence on the urinary losses of zinc, copper, iron, and calcium. Limited experience to date in man has revealed no significant adverse side effects of DMSA. In animals, DMSA will promptly reduce the concentration of lead in brain and kidney, in particular. By contrast, similar 5-day courses of CaNa2EDTA do not produce any net reduction in brain lead. This is important, as the brain is the critical organ of the adverse effects of lead in children. If the efficacy of DMSA is to be comprehensively evaluated ethically in children, new and more sensitive neurochemical, electrophysiologic, or other markers must be developed.

Topics: Animals; Chelating Agents; Chelation Therapy; Drug Evaluation; Edetic Acid; Humans; Lead; Lead Poisoning; Succimer

Topics: Animals; Antidotes; Arsenic Poisoning; Biotransformation; Cadmium Poisoning; Dimercaprol; Forecasting; Humans; Kinetics; Lead Poisoning; Mercury Poisoning; Metals; Solubility; Succimer; Sulfhydryl Compounds; Unithiol

Succimer lowers blood lead concentrations in children, and the structure of succimer chelates of lead and cadmium are similar. Using blood samples from a randomized trial of succimer for lead poisoning, however, we found that succimer did not lower blood cadmium in children with background exposure.

Topics: Cadmium; Chelating Agents; Chelation Therapy; Child; Environmental Exposure; Humans; Lead Poisoning; Succimer

The aim of this study was to explore therapeutic efficiency of succimer used with calcium and ascorbic acid in the treatment of mildly lead-poisoned mice and preschool children. Mice were exposed to lead by drinking water, and then treated with saline solution, 50mg/kg body weight (b.w.) succimer, 100mg/kg b.w. succimer, or 50mg/kg b.w. succimer plus calcium and ascorbic acid by gavage. Seventy-two children aged 48-72 months were randomly assigned into combined treatment or nutritional intervention group. Lead levels in blood and bone were analyzed by atomic absorption spectrophotometry. Activities of aminolevulinic acid dehydratase (ALAD) in blood were determined by colorimetric method. Results of animal experiment showed that succimer used alone could reduce lead levels in blood and bone and reverse activities of ALAD in blood, however, a better therapeutic efficiency in mobilizing bone lead could be achieved by succimer used with calcium and ascorbic acid. Findings from the clinical study showed that reduction of blood lead levels (BLLs) between the end and initiation of therapy in the combined treatment group was significantly greater than that in the nutritional intervention group. Percentage of children with BLLs less than 10μg/dL at the end of therapy and the eighth week after therapy in the combined treatment group was significantly higher than that in the nutritional intervention group. In conclusion, combined use of succimer with calcium and ascorbic acid seemed to be a choice in the treatment of mildly lead poisoned children.

Topics: Aging; Animals; Ascorbic Acid; Bone and Bones; Calcium Carbonate; Chelating Agents; Child; Child, Preschool; Colorimetry; Environmental Exposure; Female; Free Radical Scavengers; Humans; Lead; Lead Poisoning; Male; Mice; Porphobilinogen Synthase; Succimer

The lead mobilization test reflects the mobilizable and likely toxicologically active fraction of the lead body burden. We propose a safe and convenient protocol for this test, to assess concomitant copper and zinc excretion and to determine the size of the chelatable lead pool in nonoccupationally exposed adults.. The study population included 80 white adults: 40 controls [median blood lead concentration (PbB), 25 microg/L] and 40 lead-exposed individuals (315 microg/L). After collection of 4- and 24-h baseline urine specimens and a blood sample, dimercaptosuccinic acid (DMSA) was administered orally (1 g), and additional 4- and 24-h urine specimens were obtained. Determinants of the chelatable urinary lead (DMSA-PbU) were traced by linear regression analysis.. Urinary DMSA and lead excretion peaked within 2-3 h after DMSA administration. The amounts of DMSA, lead, copper, and zinc recovered in the 4-h urinary collections were highly correlated with those in 24-h collections (r = 0.857, 0.859, 0.958, and 0.757, respectively). At PbB concentrations >300 microg/L, the relationship between DMSA-PbU and PbB showed a steep increase and a widespread dispersion of DMSA-PbU around the regression line. After DMSA, copper and zinc excretion rates were increased up to 91- and 33-fold, respectively. No side effects were reported after DMSA.. Determination of DMSA-PbU in a 4-h collection after DMSA is convenient, apparently safe, and inexpensive. An upper reference limit value of 22 microg/4 h is proposed for Belgian reference individuals. The diagnostic value of DMSA-PbU is likely to be contributive for PbB >300 microg/L.

Topics: Adult; Chelating Agents; Copper; Environmental Pollutants; Female; Humans; Lead; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer; Zinc

Increases in peak blood lead concentrations, which occur at 18-30 months of age in the United States, are thought to result in lower IQ scores at 4-6 years of age, when IQ becomes stable and measurable. Data from a prospective study conducted in Boston suggested that blood lead concentrations at 2 years of age were more predictive of cognitive deficits in older children than were later blood lead concentrations or blood lead concentrations measured concurrently with IQ. Therefore, cross-sectional associations between blood lead and IQ in school-age children have been widely interpreted as the residual effects of higher blood lead concentrations at an earlier age or the tendency of less intelligent children to ingest more leaded dust or paint chips, rather than as a causal relationship in older children. Here we analyze data from a clinical trial in which children were treated for elevated blood lead concentrations (20-44 microg/dL) at about 2 years of age and followed until 7 years of age with serial IQ tests and measurements of blood lead. We found that cross-sectional associations increased in strength as the children became older, whereas the relation between baseline blood lead and IQ attenuated. Peak blood lead level thus does not fully account for the observed association in older children between their lower blood lead concentrations and IQ. The effect of concurrent blood level on IQ may therefore be greater than currently believed.

Topics: Age Factors; Chelating Agents; Child; Child Development; Child, Preschool; Cognition Disorders; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Female; Humans; Intelligence; Lead; Lead Poisoning; Male; Placebos; Succimer

Growth deficits associated with lead exposure might be ameliorated by chelation. We examined the effect of succimer on growth in 780 children 12-33 months old who had blood lead levels of 20-44 microg/dL and were randomized to receive up to three 26-day courses of succimer or placebo in a multicenter, double-blind trial. The difference in changes in weight and height between succimer and placebo groups at 1-34 months was calculated by fitting cubic splines. The difference in height change in children on succimer compared with placebo was -0.27 cm [95% confidence interval (95% CI), -0.42 to -0.11] from baseline to 9 months, when 99% of children had completed treatment, and -0.43 cm (95% CI, -0.77 to -0.09) during 34 months of follow-up. Similar differences in weight gain were not statistically significant. Although succimer lowers blood lead in moderately lead-poisoned children, it does not have a beneficial effect on growth and may have an adverse effect.

Topics: Body Height; Body Weight; Chelating Agents; Child Development; Double-Blind Method; Female; Growth; Humans; Infant; Lead Poisoning; Male; Placebos; Succimer; Treatment Outcome

Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems. It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity. The objective of this study was to determine whether chelation therapy with succimer (dimercaptosuccinic acid) in children with referral blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years.. The Treatment of Lead-Exposed Children (TLC) study is a randomized, double-blind, placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia, PA; Newark, NJ; Cincinnati, OH; and Baltimore, MD. Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility, 780 were randomized to the active drug and placebo groups stratified by clinical center, body surface area, blood lead level, and language spoken at home. At 7 years of age, 647 subjects remained in the study. Participants were randomly assigned to receive oral succimer or placebo. Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug. Eighty-nine percent had finished treatment by 6 months, with all children finishing by 13 months after randomization. All participants received residential lead hazard control measures before treatment. TLC subjects also received a daily multivitamin supplement before and after treatment(s) with succimer or placebo. Scores on standardized neuropsychological measures that tap cognition, behavior, learning and memory, attention, and neuromotor skills were measured.. Chelation therapy with succimer lowered average blood lead levels for approximately 6 months but resulted in no benefit in cognitive, behavioral, and neuromotor endpoints.. These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 microg/dL (0.96-2.17 micromol/L). These results emphasize the importance of taking environmental measures to prevent exposure to lead. Chelation therapy with succimer cannot be recommended for children with blood lead levels between 20 and 44 microg/dL (0.96-2.12 micromol/L).

Topics: Chelating Agents; Chelation Therapy; Child; Child Behavior; Child Development; Child, Preschool; Double-Blind Method; Environmental Exposure; Humans; Infant; Intelligence; Lead; Lead Poisoning; Neuropsychological Tests; Succimer

To compare the efficacy of calcium disodium EDTA (CaNa2EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) in reducing concentrations of lead in selected tissues for use in treatment of calves with experimentally induced lead toxicosis.. 19 sexually intact male Holstein calves that weighed 35 to 60 kg.. Calves were randomly assigned to 1 of 5 treatment groups: group 1, control calves; group 2, lead only; group 3, lead and EDTA; group 4, lead and DMSA; and group 5, lead, EDTA, and DMSA. Calves in groups 2 to 5 were dosed daily with lead (5 mg/kg, PO) for 10 days. Doses of EDTA (100 mg/kg) and DMSA (25 mg/kg) were administered IV once daily for 4 consecutive days beginning on day 11. Effects of the chelators on lead concentrations in the liver, kidneys, testes, muscles, bones, and brain were compared among the various groups.. Compared with the effects of EDTA, DMSA greatly reduced lead concentrations in renal and hepatic tissues. We did not detect significant differences for the effects of EDTA or DMSA on lead concentrations in the testes; there was an adverse interaction of EDTA with DMSA that caused an increase in lead concentrations in the testes.. DMSA is much more effective than EDTA in removing lead from renal and hepatic tissues in calves. Use of DMSA in calves with lead intoxication appears to be a viable treatment option. Combining DMSA and EDTA as a treatment modality in calves did not offer any advantages.

Topics: Animals; Bone and Bones; Brain Chemistry; Cattle; Chelating Agents; Drug Therapy, Combination; Edetic Acid; Kidney; Lead; Lead Poisoning; Liver; Male; Muscle, Skeletal; Succimer; Testis

Exposure to lead at levels encountered by urban children impairs cognitive development. An observational study suggested improvement in IQ when blood lead level fell, but the only randomized trial of chelation showed no benefit in IQ.. We did a new analysis of the data from the clinical trial using change in blood lead level as the independent variable. The 741 children began with blood lead levels between 20 and 44 microg/dL, and were 13 to 33 months old at randomization to chelation or placebo. Blood lead levels were measured repeatedly, and cognitive tests were given at baseline, 6 months, and 36 months follow-up.. By 6 months after randomization, blood lead levels had fallen by similar amounts in both chelated and placebo children, despite the immediate drops in the chelated group; there was no association between change in blood lead level and change in cognitive test score. Blood lead levels continued to fall. At 36 months follow-up, in the placebo group only, cognitive test scores had increased 4.0 points per 10 microg/dL fall in blood lead level from baseline to 36 months follow-up and 5.1 points from 6 to 36 months.. The improvement in scores in the placebo group only implies that factors other than declining blood lead levels per se are responsible for cognitive improvement; it is possible but less likely that succimer, the active drug, impairs cognition.

Topics: Chelating Agents; Child Development; Child, Preschool; Cognition Disorders; Double-Blind Method; Female; Humans; Infant; Lead; Lead Poisoning; Male; Neuropsychological Tests; Placebos; Succimer; Treatment Outcome

Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment.. We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months.. During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter [0.2 to 0.3 micromol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant.. Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 microg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels.

Topics: Chelating Agents; Chelation Therapy; Child Behavior; Child Development; Child, Preschool; Cognition; Double-Blind Method; Female; Humans; Infant; Intelligence; Lead; Lead Poisoning; Male; Neuropsychological Tests; Poverty Areas; Succimer; Urban Population

To evaluate the safety and efficacy of meso-2,3-dimercaptosuccinic acid in the treatment of children with lead toxicity.. This was an open-label study in 59 children 12-65-months old, with pretreatment whole-blood lead levels of 25-66 microg/dL, who received 116, 26-28 day courses of oral dimer-captosuccinic acid, while residing either in the Pediatric Clinical Research Unit of the Johns Hopkins Hospital or in lead-safe housing during the outpatient portion of the study.. All, who completed the study, showed sharp decreases in blood lead concentration during therapy, but 2-3 weeks following completion of drug therapy, blood lead concentration rebounded to an average of 58% (23 microg Pb/dL of whole blood) of their average pretreatment blood lead concentration (40 microg Pb/dL of whole blood). There were no adverse reactions attributable to dimercaptosuccinic acid; however, 2 of the 59 patients were reexposed to defective lead paint and experienced sharp increases in blood lead concentration while on therapy. In one instance, the child's blood lead concentration increased from 20 to 90 microg Pb/dL whole blood in 1 week. Other unexpected events were discussed in the text.. Dimercaptosuccinic acid is apparently safe and does mobilize lead into the urine, but not the essential metals, zinc and copper. Reexposure is always a danger; therefore, all children, while on therapy, should be monitored for their blood lead concentration at weekly intervals during and immediately after therapy. No conclusions can be drawn from this study regarding long-term beneficial effects, if any, of this drug on late neurocognitive outcome.

Topics: Administration, Oral; Alkaline Phosphatase; Anemia, Sickle Cell; Antidotes; Chelating Agents; Child; Child, Preschool; Copper; Creatinine; Demography; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Infant; Lead; Lead Poisoning; Male; Metabolic Clearance Rate; Succimer; Treatment Outcome; Zinc

This study evaluates the effectiveness (use under routine circumstances) of DMSA (2,3 dimercaptosuccinic acid) and environmental remediation as compared with placebo and environmental remediation on children with blood lead (BPb) levels of 30-45 micrograms/dL (1.45-2.17 mumol/L). The endpoints were BPb at 1 month and 6 months after study entry. This double-blind placebo-controlled trial involved 39 children aged 2-5 years, who were randomized to one course of DMSA or placebo. The mean BPb levels of the two groups at study entry were similar, placebo group 33.0 micrograms/dL (1.59 mumol/L) and the DMSA group 34.9 micrograms/dL (1.68 mumol/L). At 1 month (the end of treatment) the mean BPb levels of the two groups were: placebo group 33.2 micrograms/dL (1.60 mumol/L) and the DMSA group 27.4 micrograms/dL (1.32 mumol/L), p = 0.16. At 6 months, the mean BPb levels were 25.1 micrograms/dL (1.21 mumol/L) for the placebo group and 28.8 micrograms/dL (1.39 mumol/L) for the DMSA-treated group, p = 0.06. Neither of these differences is statistically significant. All children with BPb, in the range studied here, should receive environmental evaluation and remediation; DMSA does not improve long-term blood lead levels.

Topics: Chelating Agents; Child, Preschool; Follow-Up Studies; Humans; Lead; Lead Poisoning; Succimer

Exposure to lead impairs cognitive development in young children, but the benefits of lowering blood lead pharmacologically are not clear. This report describes the design, recruitment, enrolment and baseline results of the Treatment of Lead-Exposed Children (TLC) trial, a randomised, multicentre, placebo-controlled, double-blind clinical trial of the effects of treating lead-exposed children with succimer, a drug that enhances urinary excretion of lead, on cognitive, behavioural and physical development. TLC clinical sites were in Baltimore, Cincinnati and Columbus, Newark and Philadelphia. Children were eligible for TLC if they were between 12 and 33 months of age, had a confirmed blood lead concentration between 20 and 44 micrograms/dL and lived in a residence suitable for lead dust reduction. Randomised children received up to three 26-day courses of succimer or placebo, and were then followed for 3 years. The study can detect a three-point difference in full-scale IQ at 3-year follow-up. Statistical power for the other end points is more difficult to estimate. A total of 1854 children were evaluated and 780 children were randomised between August 1994 and January 1997. The mean age of randomised children was 24 months and mean blood lead level 26 micrograms/dL. Three-quarters were African-American. Most children had poor, single mothers who had completed 12 or fewer years of school and who lived in older, poorly maintained residences.

Topics: Chelating Agents; Chelation Therapy; Child Development; Child, Preschool; Double-Blind Method; Housing; Humans; Infant; Lead; Lead Poisoning; Succimer; United States

We examined the efficacy and safety of meso-2,3-dimercaptosuccinic acid (DMSA) in children with markedly elevated blood lead (BPb) concentrations. Among 19 children with BPb concentrations of 50 to 69 micrograms/dl (2.41 to 3.33 mumol/L) who received a 5-day inpatient oral course of DMSA (1050 mg/m2 per day), the mean BPb concentration decreased by 61%; in four who received calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) (1000 mg/m2 per day intravenously), it decreased by 45% (p less than 0.0007). Urinary lead excretion was comparable in both groups. Treatment with DMSA was more effective than treatment with CaNa2EDTA in restoring metabolic activity to the heme pathway and was well tolerated even among nine patients who received concomitant iron supplementation and two who had homozygous deficiency of glucose-6-phosphate dehydrogenase. On discharge, these 19 children received either no chelation therapy or DMSA, 350 or 700 mg/m2 per day for 14 days on an outpatient basis. After 14 days the mean BPb values for the no-chelation, low-DMSA, and high-DMSA groups were 73%, 66%, and 50% of the pretreatment values, respectively. We conclude that a 5-day oral course of DMSA is effective in the treatment of children with severe lead poisoning. In addition, on an outpatient basis the administration of DMSA, 700 mg/m2 per day, is capable of delaying the typical rebound in BPb values and should ultimately reduce the need for repeated hospitalizations.

Topics: Administration, Oral; Ambulatory Care; Aminolevulinic Acid; Calcium; Chelating Agents; Child; Child, Preschool; Dimercaprol; Edetic Acid; Erythrocytes; Follow-Up Studies; Humans; Infant; Injections, Intravenous; Lead; Lead Poisoning; Porphobilinogen Synthase; Safety; Succimer; Zinc

2,3-Dimercaptosuccinic acid (DMSA) is an orally effective orphan drug that is more specific and has a wider therapeutic index than other currently available drugs used for lead intoxication. Its investigational use in the United States has been limited to the treatment of men with occupational plumbism. Twenty-one children with blood lead concentrations of 31 to 49 micrograms/dl, who also had a positive calcium disodium edetate (CaNa2EDTA) mobilization test result, were hospitalized for 7 days. Fifteen children were randomly assigned to three groups that received either 350, 700, or 1050 mg/m2/day, respectively, of DMSA in three divided doses daily. A fourth group of six children received conventional treatment with 1000 mg/m2/day of intravenously administered CaNa2EDTA in two divided doses daily. The 1050 mg/m2/day dose of DMSA was significantly more effective than lower doses of DMSA or intravenously administered CaNa2EDTA in reducing blood lead levels and restoring erythrocyte delta-aminolevulinic acid dehydratase activity. Intravenously administered CaNa2EDTA significantly increased the urinary excretion of several essential minerals (zinc, copper, iron, and calcium), whereas DMSA did not. The DMSA was well tolerated and appears extremely promising as a drug that will simplify the management of childhood lead poisoning.

Topics: Administration, Oral; Child; Child, Preschool; Drug Administration Schedule; Edetic Acid; Humans; Lead Poisoning; Minerals; Random Allocation; Sensitivity and Specificity; Succimer; Sulfhydryl Compounds

A 38-year-old man with a tibial plateau fracture required treatment for elevated blood lead level (BLL) from retained bullet fragments in the same knee from a gunshot wound 21 years earlier. Oral succimer presurgery and postsurgery decreased the BLL from 58 to 15 μg/dL.. Parenteral chelation has been previously recommended to mitigate an increase in BLLs during surgical intervention to remove bullet fragments. Oral succimer was an effective and well-tolerated alternative to intravenous chelation. Further research is needed to determine the optimal route, timing, and duration of chelation in patients with elevated BLL in need of bulletectomy.

Topics: Adult; Chelating Agents; Humans; Lead; Lead Poisoning; Male; Succimer; Wounds, Gunshot

Antenatal lead exposure is associated with multiple adverse maternal and fetal consequences. Maternal blood lead concentrations as low as 10 µg/dL have been associated with gestational hypertension, spontaneous abortion, growth retardation, and impaired neurobehavioral development. Current treatment recommendations for pregnant women with a blood lead level (BLL) ≥ 45 µg/dL include chelation. We report a successful case of a mother with severe gestational lead poisoning treated with induction of labor in a term infant.. A 22-year-old G2P1001 female, at 38 weeks and 5 days gestation, was referred to the emergency department for an outpatient venous BLL of 53 µg/dL. The decision was made to limit ongoing prenatal lead exposure by emergent induction as opposed to chelation. Maternal BLL just prior to induction increased to 70 µg/dL. A 3510 g infant was delivered with APGAR scores of 9 and 9 at 1 and 5 min. Cord BLL at delivery returned at 41 µg/dL. The mother was instructed to avoid breastfeeding until her BLLs decreased to below 40 µg/dL, consistent with federal and local guidelines. The neonate was empirically chelated with dimercaptosuccinic acid. On postpartum day 2, maternal BLL decreased to 36 µg/dL, and the neonatal BLL was found to be 33 µg/mL. Both the mother and neonate were discharged to an alternative lead-free household on postpartum day 4.

Topics: Adult; Chelating Agents; Female; Humans; Infant; Infant, Newborn; Labor, Induced; Lead; Lead Poisoning; Pregnancy; Succimer; Young Adult

Lead is a toxic substance in our environment that affects adults and children of all socioeconomic backgrounds, lead poisoning is one of the most common exposures that can cause inter alia significant neurological and functional damage in humans. Children are particularly vulnerable because of the effects of the toxicity on their developing nervous systems with potentially irreversible consequences. We report a case of severe lead poisoning encephalo-neuropathy in a 3-year-old girl, admitted for progressive paraplegia, swallowing disorders, and aphasia. A multitude of investigations undertaken could not explain her atypic symptoms, so anamnesis was redone in the sense of a toxic origin, we found a notion of pica, and a traditional herbalist father, so probably consumption of medications based on traditional medicine products. A venous blood lead level (BLL) was extremely elevated at 176.4 μg/l. The child was treated with an oral chelator succimer (SUCCICAPTAL). During the two following months in the intensive care unit, the child showed progressive respiratory distress and worsening signs of the nervous system. Despite treatment and the use of lead chelators, the patient died due to septic shock. Lead is highly toxic even at very low exposure levels, at high levels of exposure, it can damage the reproductive organs, immune system, liver and kidneys. in children, it can affect neurocognitive and behavioral development that could be irreversible. Peripheral and central nervous system damage should be considered as a possible manifestation of lead poisoning.

Topics: Brain; Child; Child, Preschool; Family; Female; Humans; Lead; Lead Poisoning; Peripheral Nervous System Diseases; Succimer

Chronic lead poisoning has become a major factor in global public health. Chelation therapy is usually used to manage lead poisoning. Dimercaptosuccinic acid (DMSA) is a widely used heavy metal chelation agent. However, DMSA has the characteristics of poor water solubility, low oral bioavailability, and short half-life, which limit its clinical application. Herein, a long-cycle slow-release nanodrug delivery system was constructed. We successfully coated the red blood cell membrane (RBCM) onto the surface of dimercaptosuccinic acid polylactic acid glycolic acid copolymer (PLGA) nanoparticles (RBCM-DMSA-NPs), which have a long cycle and detoxification capabilities. The NPs were characterized and observed by particle size meters and transmission electron microscopy. The results showed that the particle size of RBCM-DMSA-NPs was approximately 146.66 ± 2.41 nm, and the zeta potential was - 15.34 ± 1.60 mV. The homogeneous spherical shape and clear core-shell structure of the bionic nanoparticles were observed by transmission electron microscopy. In the animal tests, the area under the administration time curve of RBCM-DMSA-NPs was 156.52 ± 2.63 (mg/L·h), which was 5.21-fold and 2.36-fold that of free DMSA and DMSA-NPs, respectively. Furthermore, the median survival of the RBCM-DMSA-NP treatment group (47 days) was 3.61-fold, 1.32-fold, and 1.16-fold for the lead poisoning group, free DMSA, and DMSA-NP groups, respectively. The RBCM-DMSA-NP treatment significantly extended the cycle time of the drug in the body and improved the survival rate of mice with chronic lead poisoning. Histological analyses showed that RBCM-DMSA-NPs did not cause significant systemic toxicity. These results indicated that RBCM-DMSA-NPs could be a potential candidate for long-term chronic lead exposure treatment.

Topics: Animals; Antidotes; Biomimetics; Heavy Metal Poisoning; Lead Poisoning; Mice; Nanoparticles; Succimer

Topics: Chelating Agents; Humans; Lead Poisoning; Succimer

Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning.. In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens.. Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients.. Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.

Topics: Adult; Antidotes; Cost-Benefit Analysis; Cross-Sectional Studies; Drug Therapy, Combination; Garlic; Humans; Iran; Lead; Lead Poisoning; Male; Penicillamine; Phytochemicals; Retrospective Studies; Succimer; Treatment Outcome

The effect of combined administration of calcium (Ca), iron (Fe), zinc (Zn), chrysanthemum flavonoids, and meso-2,3-dimercaptosuccinic acid (DMSA) on the treatment of lead (Pb) intoxication in mice was studied. One hundred ninety female mice (SPF level, aged 18-22 days) were randomly divided into two groups as experimental animals. Mice in group I (10 mice) served as normal control animals, and were administered deionized water containing 12.5 μL/L acetate acid for 6 weeks, whereas mice in group II (180 mice) were exposed to 0.1% (wt/vol) of lead acetate in deionized water for 6 weeks and served as experimental animals. After 6 weeks of successful modeling, 180 mice from group II (lead-exposed) were divided into 18 groups of 10 mice each, 16 of which were treated by the combined administration of Ca, Fe, Zn, chrysanthemum flavonoids, and DMSA by L

Topics: Animals; Calcium; Chrysanthemum; Disease Models, Animal; Drug Therapy, Combination; Female; Flavonoids; Glutathione; Glutathione Peroxidase; Hippocampus; Iron; Lead; Lead Poisoning; Liver; Malondialdehyde; Mice; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Plant Extracts; Porphobilinogen Synthase; Succimer; Superoxide Dismutase; Treatment Outcome; Zinc

Topics: Edetic Acid; Humans; Infant; Lead; Lead Poisoning; Male; Paint; Radiography, Abdominal; Succimer

Lead (Pb) is observed in all areas of the environment, mainly derived from human operations such as mining, processing, and burning fossil fuels. Pb toxicity is one of the most prevalent causes of human hepatotoxicity. The available chelator drugs used now have many adverse effects and therefore the world is looking for natural and secure alternatives.. Here, we evaluated the hepatoprotective role of the oral administration (1 g/kg b.w.) of the lyophilized Beta vulgaris juice (BVJ) against Pb-induced rat hepatotoxicity. We also examined the possible synergistic hepatoprotective impact of the combination between BVJ and 2,3- dimercaptosuccinic acid (DMSA, the currently approved drug for Pb-toxicity). The evaluation depends on the ability of BVJ, DMSA, or their combination (BVJ-DMSA) to reduce serum and hepatic Pb level and to avoid oxidative stress and inflammation caused by Pb. The level of lipid peroxidation, reduced glutathione (GSH), total antioxidant capacity, and the activity of the antioxidant enzymes were quantified. In addition, the level of interleukin (IL)-6, nitric oxide (NO), DNA fragmentation, and liver histology were studied.. The results showed that BVJ contained considerable amounts of betalains, vitamin C, and various types of phenolic compounds. Therefore, BVJ displayed a significant (p < 0.05) preventive influence on the elevation of Pb levels in blood and liver as well as the hepatic DNA fragmentation. In addition, it significantly (p < 0.05) improved most of the studied antioxidant and inflammatory markers in the Pb-intoxicated rats. However, the combined extract (BVJ-DMSA) revealed synergistic (combination index < 1) activities in most of the tested parameters. The histopathological results verified the biochemical findings of this research.. BVJ has a potent efficiency in the protection from Pb-induced hepatotoxicity through the reduction of its accumulation in blood and liver and the prevention of the oxidative stress and inflammation induced by Pb. Additionally, the treatment of hepatotoxicity with BVJ and DMSA in combination showed a synergistic effect and reduced the adverse effects induced by DMSA. Thus, BVJ can be a promising hepatoprotective extract against lead toxicity and its combination with DMSA potentiates this effect.

Topics: Administration, Oral; Animals; Antioxidants; Beta vulgaris; Chelating Agents; Disease Models, Animal; Drug Synergism; Egypt; Fruit and Vegetable Juices; Inflammation; Lead; Lead Poisoning; Liver; Male; Oxidative Stress; Rats; Succimer

To explore the impacts of Pb exposure and the dimercaptosuccinic acid (DMSA) chelation therapy on bone metabolisms in young rats of different ages, as well as the potential mechanisms.. Young rats were exposed to 0.05%-0.1% Pb acetate for 19 days, during infanthood (postnatal day, PND2-20), childhood (PND21-39) and adolescenthood (PND40-58) respectively. In each developmental stage, rats were further divided into three subgroups: lead-exposed, one-course and two-course DMSA chelation therapy subgroups. Blood/bone lead concentrations, serum calciotropic hormones concentrations, and mRNA and protein expressions of bone turnover markers in the serum and bones were measured. Bone microstructures were analyzed using Micro-CT.. Compared with lead-exposed during childhood and adolescenthood, increases in blood/bone lead levels, and the changes of blood/bone lead and trabecular bone microstructures after one-course DMSA chelation were most significant in rats lead-exposed during infanthood (P < .05). The serum osteocalcin (OC) concentrations, mRNA/protein expressions of OC and runt-related transcription factor 2 (RUNX2) in bones all decreased after Pb exposure, along with significant increases in serum C-terminal telopeptide of type I collagen (CTX) concentrations (P < .05). These effects were accompanied by changes of serum parathormone (PTH) and 1,25-dihydroxyvitamin D. Developmental Pb exposure impaired bone microstructures and interfered bone metabolism, and the exposure effect was more obvious during infanthood than during childhood and adolescenthood. Lead effects were partially reversed by chelation therapy, and the efficacy may be most significant when the therapy was provided at younger ages.

Topics: Animals; Bone and Bones; Bone Development; Chelating Agents; Chelation Therapy; Lead; Lead Poisoning; Male; Rats; Succimer

Across the world, tobacco is used in a variety of forms, including being smoked or added to a "quid" that is then chewed. We report a case of lead poisoning in a child from tobacco imported from Thailand.. A 12-year-old Thai immigrant boy had a blood lead level (BLL) of 6 mcg/dL on routine testing upon arrival to the United States, but which increased to 72 mcg/dL six months after his arrival. He was asymptomatic with unremarkable workup. At this time his father, mother and two siblings were also found to have elevated BLLs of 53, 16, 22, and 11 mcg/dL, respectively. Water, paint, food and cookware sources tested negative for lead, whereas samples of the father's dried tobacco leaves imported from Thailand contained 36.12 ppm (mcg/g) of lead. The mother admitted that both she and the patient used the tobacco as well. The child was chelated with oral succimer and his BLL decreased.. In our case, the source of the lead exposure was from the tobacco that the patient was chewing. Tobacco is often overlooked as a source of lead exposure, though it has been reported in the literature, both from direct smoking and from chewing, as well as through secondhand smoke. Toxicologists and health care professionals should consider cultural practices when evaluating patients with elevated BLLs.

Topics: Adult; Chelating Agents; Child; Environmental Exposure; Female; Humans; Lead; Lead Poisoning; Male; Nicotiana; Succimer; Thailand; Tobacco, Smokeless; Treatment Outcome; United States

N,N`-Bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine (HTPL) is a novel newly synthesized compound intended to be used for the chelation of lead in intoxicated animals. Subchronic lead intoxication experiments were carried out on Wistar male rats; these rats were intoxicated with lead and then treated with HTPL. Results were compared with those obtained with known compounds used for lead chelation therapy, such as disodium ethylnediaminetetraacetic acid (CaNa

Topics: Animals; Chelating Agents; Chelation Therapy; Edetic Acid; Lead; Lead Poisoning; Male; Porphobilinogen Synthase; Protoporphyrins; Rats; Rats, Wistar; Succimer

Topics: Chelating Agents; Exanthema; Fever; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations.. We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations.. Pre-chelation blood lead concentrations ranged between 99 and 150 μg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others.. Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

Topics: Adolescent; Adult; Antidotes; Chelating Agents; Chelation Therapy; Humans; Lead; Lead Poisoning; Male; Medicine, Traditional; Models, Biological; Occupational Exposure; Reproducibility of Results; Succimer

Lead toxicosis occurs in veterinary patients, with few reports involving rabbits, and no previous reports using oral calcium disodium EDTA.. A 7-year-old male castrated Lionhead rabbit presented to the Cornell University Hospital for Animals (CUHA) for evaluation after a 2-day history of lethargy and a 2-week history of hyporexia. The patient had been observed pulling paint from the walls of the home, a house built circa 1900, in the months prior to presentation. The patient was moderately anemic with a hematocrit of 21% with red blood cell morphological changes consistent with lead toxicosis, including basophilic stippling, nucleated red blood cells, and polychromasia. Radiographic images of the abdomen revealed excessive accumulation of gas in the gastrointestinal tract in a pattern consistent with gastric stasis and numerous small mineral to metallic opacities in the cecum. The blood lead concentration was 792 μg/dL, confirming the diagnosis of lead toxicosis with secondary gastrointestinal stasis. The rabbit was hospitalized for treatment with oral and subcutaneous calcium disodium EDTA for 4 days and then discharged home to the care of the owners.. Severe lead toxicosis in a rabbit can be treated successfully with oral and subcutaneous calcium disodium EDTA and aggressive supportive treatment.

Topics: Animals; Antidotes; Chelating Agents; Gastroparesis; Lead; Lead Poisoning; Male; Rabbits; Succimer

This project aimed to develop and characterize a new nanoadsorbent for hemoperfusion. Fe

Topics: Adsorption; Animals; Ferrosoferric Oxide; Hemoperfusion; Lead; Lead Poisoning; Materials Testing; Nanoparticles; Rabbits; Silicon Dioxide; Succimer; Swine; Toxicity Tests

Lead (Pb) pollution is a serious public health problem all over the world, it especially plays severe damage role in children's health. Apart from reducing lead-induced damages, the decrease of lead accumulation is also critical. This study has been the first attempt to investigate effects of meso-2,3-dimercaptosuccinic acid (DMSA), potassium iodide (KI) and chlorophyll (Chl) on lead accumulation in male mice.. Eighty healthy Kunming male mice were selected and divided randomly into 8 groups. They were treated with lead acetate (PbAc) intraperitoneally, individually and in combination with the DMSA, KI or Chl once daily for 5 days. Meanwhile, the control group was treated with normal saline during the whole exposure period. On 30th day, mice were sacrificed and lead concentrations were detected in the whole blood, livers, kidneys, and testicles of mice by means of the graphite furnace atomic absorption spectrometry.. In comparison with the control group, lead concentrations increased in mice treated with the PbAc and DMSA, KI and Chl diminished lead accumulation in the whole blood, livers, and kidneys. Chl had specifically the same effects on lead concentrations in the testicles of male mice.. Potassium iodide and Chl, as food additives, had the same effects as the DMSA to reduce lead accumulation in male mice effectively. Our results provided experimental evidence in vivo for the preventive measures of lead poisoning. Int J Occup Med Environ Health 2017;30(1):87-93.

Topics: Animals; Chelating Agents; Chlorophyll; Food Additives; Kidney; Lead; Lead Poisoning; Liver; Male; Mice; Potassium Iodide; Succimer; Testis

No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning.. Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model.. This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies.. The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability.. A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.

Topics: Adult; Chelating Agents; Chelation Therapy; Humans; Lead; Lead Poisoning; Male; Models, Biological; Succimer; Young Adult

Topics: Abdominal Pain; Adolescent; Chelating Agents; Diagnosis, Differential; Dimercaprol; Edetic Acid; Female; Hematemesis; Humans; Lead Poisoning; Succimer

Topics: Chelating Agents; Humans; Infant; Lead; Lead Poisoning; Male; Medicine, Ayurvedic; Succimer; United States

Lead encephalopathy is a severe manifestation of lead poisoning that can present with altered mental status and seizures and has been associated with illicit moonshine consumption. Lead encephalopathy has traditionally been treated using dimercaprol (British anti-Lewisite, BAL) and calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA).. We describe a patient with lead encephalopathy related to lead-contaminated moonshine consumption, who was treated using dimercaptosuccinic acid (DMSA) due to a national shortage of CaNa2EDTA. A 66-year-old woman presented to a hospital with headache, irritability, and altered mental status. On hospital day 16, she was found to have a whole blood lead concentration of 148.2 μg/dL and a 24-h urine lead concentration of 232 μg/day. Due to a national shortage of CaNa2EDTA, the patient was given one dose of BAL and then started on DMSA via nasogastric tube. She dramatically improved over 4 days and was subsequently transitioned to oral DMSA and outpatient treatment. One day prior to discharge, her whole blood lead concentration was 47.2 μg/dL and her mental status was normal. DMSA was used in lieu of CaNa2EDTA to treat the patient with lead encephalopathy. The patient subsequently experienced clinical improvement and declining whole blood level concentrations.. Further prospective studies are needed to compare the efficacy of DMSA versus CaNa2EDTA in patients with lead encephalopathy.

Topics: Aged; Brain Diseases; Female; Food Contamination; Humans; Lead Poisoning; Succimer

Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes.. To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated).. Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05).. All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

Topics: Age Factors; Animals; Antihypertensive Agents; Arginine; Blood Pressure; Body Weight; Cardiovascular System; Chelating Agents; Combined Modality Therapy; Enalapril; Female; Hypertension; Lactation; Lead; Lead Poisoning; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Succimer; Time Factors; Treatment Outcome

In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge.. In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for.. Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary.

Topics: Administration, Oral; Chelating Agents; Child, Preschool; Female; Humans; Infant; Lead Poisoning; Male; Nigeria; Retrospective Studies; Succimer

A case of lead poisoning with established exposure to Ayurvedic medicines is presented. This patient migrated from India to New Zealand 8 years previously. He regularly visits India where he purchases "herbal remedies" for his wellbeing.

Topics: Adult; Chelating Agents; Humans; Lead; Lead Poisoning; Male; Medicine, Ayurvedic; Succimer

Although uncommon, lead poisoning should be considered as a differential diagnosis in cases of unexplained acute abdominal pain in both adults and children. We present the case of a 35-year-old Asian male who presented with abdominal pain and constipation secondary to lead poisoning. Initially, the source of lead exposure was not apparent; this was later found to be due to ingestion of an Ayurvedic herbal medicine for the treatment of infertility. Lead poisoning due to the ingestion of Ayurvedic remedies is well described. We discuss the diagnosis, pathophysiology and treatment of lead poisoning. This case illustrates one of the rarer medical causes of acute abdominal pain and emphasizes the need to take a thorough history (including specific questioning regarding the use of over-the-counter and traditional/ herbal remedies) in cases of suspected poisoning or drug toxicity.

Topics: Abdominal Pain; Acute Pain; Adult; Chelating Agents; Constipation; Diagnosis, Differential; Humans; Hypogonadism; Lead; Lead Poisoning; Male; Medicine, Ayurvedic; Plant Preparations; Succimer; Treatment Outcome

A 29-year-old man, who recently emigrated from India, presented with a 2-week history of abdominal pain, as well as nausea, constipation, and fatigue. He underwent removal of a parathyroid adenoma 6 weeks prior to admission and received a locally made Indian traditional medicine (Ayurveda) for pain control; however, this information was not initially available. He was instructed to take approximately 15 g/day. Initial evaluation revealed a normocytic anemia, but other workup including imaging and endoscopy was unrevealing. Given his recent use of Ayurvedic medicines, we tested for lead poisoning and found a blood lead level of 72 mcg/dl. We sent his medicine for analysis and found it had a high lead concentration of 36,000 mcg/g, which is over 25,000 times the maximum daily dose. He improved with cessation of the medicine and treatment with succimer. Lead poisoning can present with a variety of nonspecific signs and symptoms, including abdominal pain and anemia. Ayurvedic medicines, as well as traditional medicines from other cultures, may be a source of lead or other heavy metals. It is essential for physicians to be aware of adverse effects of Ayurvedic medicines as they are easily available and increasing in popularity.

Topics: Abdominal Pain; Adult; Anemia; Humans; Lead Poisoning; Male; Medicine, Ayurvedic; Succimer

Lead causes a broad range of adverse effects in humans and animals. The objective was to evaluate the potency of lactobacilli to bind lead in vitro and the protective effects of a selected Lactobacillus plantarum CCFM8661 against lead-induced toxicity in mice. Nine strains of bacteria were used to investigate their binding abilities of lead in vitro, and L. plantarum CCFM8661 was selected for animal experiments because of its excellent lead binding capacity. Both living and dead L. plantarum CCFM8661 were used to treat 90 male Kunming mice during or after the exposure to 1 g/L lead acetate in drinking water. The results showed oral administration of both living and dead L. plantarum CCFM8661 offered a significant protective effect against lead toxicity by recovering blood δ-aminolevulinic acid dehydratase activity, decreasing the lead levels in blood and tissues, and preventing alterations in the levels of glutathione, glutathione peroxidase, malondialdehyde, superoxide dismutase, and reactive oxygen species caused by lead exposure. Moreover, L. plantarum CCFM8661 was more effective when administered consistently during the entire lead exposure, not after the exposure. Our results suggest that L. plantarum CCFM8661 has the potency to provide a dietary strategy against lead toxicity.

Topics: Animals; Biomarkers; Chelating Agents; Chelation Therapy; Hot Temperature; Lactobacillus plantarum; Lead; Lead Poisoning; Male; Mice; Mice, Inbred Strains; Microbial Viability; Organometallic Compounds; Oxidative Stress; Porphobilinogen Synthase; Probiotics; Random Allocation; Reactive Oxygen Species; Succimer; Tissue Distribution

Lead poisoning from gunshot wounds is unusual. Awareness of this rare but serious complication can guide the physician in making a prompt diagnosis. We present a case of a 30-year-old male who had a remote history of a gunshot wound in the right knee and presented with right knee pain. Plain film showed intrarticular invasion of the bullet fragments. He was also found to have microcytic anemia with high blood lead levels. Chelation therapy was immediately started, followed with surgical removal of the bullet fragments. Lead intoxication is a rare but fatal complication of gunshot wounds. After a timely diagnosis, chelation therapy should be immediately started.

Topics: Adult; Chelating Agents; Chelation Therapy; Diagnosis, Differential; Humans; Knee Injuries; Lead Poisoning; Male; Succimer; Wounds, Gunshot

Lead (Pb) toxicity is one of the commonest environmental problems in our life; it causes many reversible and irreversible changes in our tissues. This study was carried out to investigate the effect of meso-2,3-dimercaptosuccinic acid (DMSA) on treatment of oxidative stress caused by lead poisoning in rabbits. Lead acetate (Pb(Ac)(2)) was orally administrated to rabbits for 21 days and then treated by DMSA for another 21 days. The effect of this treatment was investigated by measuring 2 of the apoptosis proteins p53 and Bcl2. Also, the auto-oxidation rate and their histopathological changes in brain, bone and liver were investigated. Hemoglobin auto-oxidation rate is measured as well as histopathological study of liver. Our data indicate that exposure to rabbits to Pb(Ac)(2) caused a significant increase of apoptosis protein p53 and decrease in the antiapoptotic BCl2 proteins.

Topics: Animals; Bone and Bones; Brain; Chelating Agents; Disease Models, Animal; Lead Poisoning; Liver; Male; Organometallic Compounds; Oxidation-Reduction; Oxidative Stress; Oxyhemoglobins; Proto-Oncogene Proteins c-bcl-2; Rabbits; Succimer; Tumor Suppressor Protein p53

A case of lead exposure resulting from the accidental ingestion of a lead-containing solution is reported. Because of clinical management rapidly performed through chelation therapy by 2,3-dimercaptopropane sulfonate sodium and meso-2,3-dimercaptosuccinic acid, blood lead levels of this 51-year-old patient were moderate (412.9 μg/L) and no clinical symptoms were observed. Numerous blood and urine samples were collected for kinetic analysis of lead elimination. However, we report the first case in which hair samples were analyzed to determine the excretion level of lead after acute intoxication.

Topics: Chelating Agents; Chelation Therapy; Female; Hair; Humans; Kinetics; Lead; Lead Poisoning; Middle Aged; Succimer; Unithiol

Few recommendations exist for management of chronic lead toxicity in instances when the source of lead exposure cannot be removed.. We describe 2 patients who had shotgun wounds resulting in multiple retained lead pellets. They developed elevated blood lead levels and were treated with 2 weeks of high-dose oral succimer before being placed on maintenance oral succimer therapy with the goal of sustaining suppressed lead levels.. Retained lead pellets have been associated with increasing blood lead levels over time. Chronic lead toxicity can cause significant morbidity. Few treatments for lead toxicity are available, and there is scarce data on maintenance therapy for patients who have large numbers of retained shotgun pellets.. This case series documents 2 patients who continue on maintenance oral chelation therapy with succimer in an effort to prevent the sequelae of chronic lead toxicity by maintaining blood lead levels less than 20 μg/dL.

Topics: Adult; Chelating Agents; Female; Foreign Bodies; Humans; Lead; Lead Poisoning; Male; Succimer; Wounds, Gunshot

The coupling of the 1-carboxyl of DMSA with l-amino acids led to a class of novel 1-(carbonyl-l-amino-acid)-2,3-dimercaptosuccinic acids (DMSA--amino acid conjugates, DMSA-Gly, -Ser, -Val, -Leu, -Ile, -Asn, -Asp, -Gln, -Glu, -Met, -Phe, and -Trp). In the in vivo evaluation of Pb-loaded mice, 0.4 mmol/kg of the conjugates effectively decreased the Pb levels of the femur, brain, kidney, liver, and blood, greatly enhanced urination, and increased the Pb levels of both urine and feces, while causing no redistributions of Pb to the other organs, especially to the brain. With respect to lowering the bone and brain Pb, DMSA-Ile, -Asn, -Gln, and -Met were more effective than DMSA. This benefit was attributed to their high transmembrane ability. In contrast to Pb, the essential metals such as Fe, Cu, Zn, and Ca of the treated mice were not affected by the administration of the conjugates. Silico molecular modeling predicted that the conjugates had little hepatotoxicity, except possibly for DMSA-Phe.

Topics: Amino Acid Sequence; Amino Acids; Animals; Antidotes; Lead; Lead Poisoning; Male; Mice; Succimer

Intravenous sodium calcium ethylene diamine tetra acetic acid (EDTA) and oral 2,3-dimercaptosuccinic acid (DMSA) have both been used to reduce the burden of lead in humans. Each of these agents enhances the mobilization of lead from different areas of the body - EDTA from the trabecular bone and DMSA from the soft tissue. A study of Korean battery workers revealed that EDTA appeared to increase the soft tissue burden of lead, resulting in increased levels of aminolevulinic acid and greater subsequent lead mobilization with DMSA. This case report discusses a patient with a higher-than-normal lead burden who exhibited increased tissue lead burden after intravenous EDTA. The elevated tissue burden of lead was still present, albeit lower, after five consecutive days of oral DMSA therapy. If this single case is representative of a typical human response to the use of intravenous (IV) EDTA for lead, then it suggests that all persons undergoing such treatment should be administered oral DMSA for a minimum of one week after EDTA treatment.

Topics: Cadmium; Chelation Therapy; Dose-Response Relationship, Drug; Drug Therapy, Combination; Edetic Acid; Humans; Lead; Lead Poisoning; Male; Middle Aged; Occupational Exposure; Succimer; Tissue Distribution; Treatment Outcome

Although the majority of published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Ayurveda is a system of traditional medicine that is native to India and is used in many parts of world as an alternative to standard treatment regimens. Here, we report the case of a 58-year-old woman who presented with abdominal pain, anemia, liver function abnormalities, and an elevated blood lead level. The patient was found to have been taking the Ayurvedic medicine Jambrulin prior to presentation. Chemical analysis of the medication showed high levels of lead. Following treatment with an oral chelating agent, the patient's symptoms resolved and laboratory abnormalities normalized. This case highlights the need for increased awareness that some Ayurvedic medicines may contain potentially harmful levels of heavy metals and people who use them are at risk of developing associated toxicities.

Topics: Chelating Agents; Drug Contamination; Female; Humans; Lead Poisoning; Medicine, Ayurvedic; Middle Aged; Plant Preparations; Succimer

In the present study, an attempt has been made to analyze the changes in the biochemical and mineral contents of lead-intoxicated bones of Catla catla at subchronic (15.5 ppm) exposure, and also to determine whether the effects of Pb intoxication can be reversed with the chelating agent meso 2, 3-dimercaptosuccinic acid (DMSA) on the bones of freshwater fingerlings Catla catla by using Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and atomic absorption spectrophotometer techniques. The FT-IR spectra of the lead-exposed bones show significant alteration in the biochemical constituents. The XRD analysis showed a decrease in crystallinity due to lead exposure. Further, the Ca, Mg, and P contents of the lead-exposed bones were less than those of the control group, and there was an increase in the mineral contents of the bones after DMSA treatment. In conclusion, the present study suggests that the subchronic lead exposure results in severe loss of bone minerals. The overall decrease in the FT-IR band intensity of Pb-exposed bones relative to the control indicates a decrease in the biochemical constituents like proteins and lipids. The increase in the band intensity after treatment with chelating agent DMSA indicates increased biochemical constituents, showing that the subchronic effects of lead can be reversed by DMSA. The amide I bands observed at 1654 cm(-1) in the present study suggest that the protein is dominated by alpha-helical structure.

Topics: Animals; Bone and Bones; Bone Density; Cyprinidae; Lead; Lead Poisoning; Succimer; Water Pollutants, Chemical

It has been shown that garlic and its main bioactive component, allicin, as natural chelating agents can reduce blood and tissue lead content in animal models. In this study the effect of allicin, alone or combined with meso-2,3-dimercaptosuccinic acid (DMSA), in decreasing lead content of blood and tissues of mice was evaluated. Swiss albino mice were exposed to 1000 ppm of lead in water for 35 days and then placed in various treatment groups including groups administered oral allicin, DMSA, or their combination. The concentrations of lead in blood, kidney, liver, bone and brain were measured using atomic absorption spectrophotometry. Both, allicin and DMSA decreased the blood and tissue lead concentration. There was an additive effect of the combined administration of allicin and DMSA in reducing bone lead. No side effect was observed in all treated groups. Combined use of DMSA and allicin seems to be a better choice in the treatment of chronic lead intoxication.

Topics: Animals; Bone and Bones; Chelating Agents; Disulfides; Drug Synergism; Drug Therapy, Combination; Female; Garlic; Lead; Lead Poisoning; Mice; Phytotherapy; Succimer; Sulfinic Acids

We report a case of total hyperpigmentation of the skin, severe itching, muscle weakness and thrombocytosis. Laboratory investigation showed white blood cell (WBC) 8.2 x 10(6)/L, Hb 125 g/L, platelets 1221 x 10(6)/L and urinary lead after DMSA mobilization test 2684 mcg/g creatinine (normal <5). Chelation therapy with DMSA resulted in complete recovery of the hyperpigmentation, itching and thrombocytosis. Lead poisoning should be considered in the differential diagnosis of obscured thrombocytosis.

Topics: Chelating Agents; Chelation Therapy; Chronic Disease; Coloring Agents; Humans; Lead Poisoning; Male; Middle Aged; Succimer; Thrombocytosis

During pregnancy skeletal lead is mobilized by maternal bone turnover and can threaten fetal development. The exact strategy suggested to women of childbearing age, who were chronically exposed to lead, and, thus, have high bone lead burden, is not well established. We describe 4 years of follow-up of a 29-year-old woman with chronic lead intoxication. We (a) advised her to delay conception until 'toxicological clearance', (b) treated her with multiple courses of lead chelator, DMSA, and (c) prescribed oral calcium. Patient had low blood lead and protoporphyrin level during pregnancy until delivery. Delaying conception, lead chelation, and calcium supplementation can decrease fetal exposure.

Topics: Adult; Calcium; Chelating Agents; Female; Fetal Diseases; Humans; Lead Poisoning; Pregnancy; Prenatal Exposure Delayed Effects; Succimer

Smilax glabra Roxb. is a traditional Chinese herb, the rhizome of Smilax glabra has been used in folk medicine for the treatment of lead poisoning.. The present study was conducted to investigate the protective role of Smilax glabra extract (SGE) individually or combined with meso-2,3-dimercaptosuccinic acid (DMSA) against the effects of lead acetate on oxidative stress and lead burden in rats.. The biochemical parameters and enzymes in different treated rats were determined by commercial kits. The metal concentrations were measured using atomic absorption spectrophotometer.. SGE (300 mg/kg) showed very low toxicity to organs in non-lead exposed rats. Administration of SGE individually had no effect on blood zinc protoporphyrin (ZPP) level but significantly enhanced the glutathione (GSH) content and delta-aminolevulinic acid dehydratase (ALAD), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in lead exposed rats. The co-treatment of SGE and DMSA had a synergism in increasing brain, liver and kidney superoxide dismutase (SOD), catalase (CAT) activities and GSH level, and decreasing oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS) levels. Moreover, the co-treatment could improve the hepatic and renal histopathology changes. SGE as chelating agent showed significant efficiency in reducing blood and tissue lead burden.. The in vivo results suggested that SGE individually or combined with DMSA exhibited remarkable protective effects on lead-induced oxidative stress and lead burden in rats.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Antidotes; Antioxidants; Body Burden; Brain; Catalase; Chelating Agents; Disease Models, Animal; Flavonoids; Glutathione; Kidney; Lead Poisoning; Liver; Male; Organometallic Compounds; Oxidative Stress; Phenols; Plant Extracts; Porphobilinogen Synthase; Protoporphyrins; Rats; Rats, Wistar; Rhizome; Smilax; Succimer; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

2,3-Dimercaptosuccinic acid (DMSA) is an orally effective chelating agent for the treatment of heavy metal poisoning. The increasing therapeutic use of DMSA has stimulated the need for sensitive and selective methods for its determination in biological samples, as well as study on pharmacokinetics and tissue distribution. According to the previously reported method, an improved method was established for the determination of DMSA in mice blood and tissues, in which oxidized DMSA was reduced by the disulfide-reducing agent, dithiothreitol (DTT), and DMSA was converted to a highly fluorescent and stable derivative by reaction with monobromobimane (mBBr) in alkaline solution. Acetonitrile was used for deproteinization and dichloromethane was used for condensation and purification, which significantly shortened the amount of time used to process the sample. Meanwhile isocratical elution was performed and excellent separation of the DMSA derivative was obtained, this enabled a run finish within 20 min. The limits of quantitation were 0.025 microg/ml in brain and 0.1 microg/ml in blood, lung, heart, intestine, liver, spleen and kidney, respectively. The calibration curves were linear in all samples (r(2)>0.992) with a range of 0.025-1.6 microg/ml for brain homogenate and 0.1-6.4 microg/ml for blood and homogenates of lung, heart, intestine, liver, spleen and kidney, respectively. Therefore, the method is simple, rapid and sensitive, and it could be applicable to the studies in an animal model to evaluate the distribution of DMSA in blood and tissues.

Topics: Animals; Blood Chemical Analysis; Chelating Agents; Chromatography, High Pressure Liquid; Female; Humans; Lead Poisoning; Male; Mice; Spectrometry, Fluorescence; Succimer

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.

Topics: Animals; Chelation Therapy; Lead; Lead Poisoning; Male; Rabbits; Succimer

Chelation therapy has been used as a means of reducing the body burden of lead for five decades. Intravenous sodium calcium edetate has been the preferred agent, but there is increasing evidence that dimercaptosuccinic acid (DMSA) is also a potent chelator of lead.. Oral DMSA 30 mg/kg/day was administered to adults with blood lead concentrations > or = 50 microg/dl. The impact of DMSA on urine lead excretion, on blood lead concentrations and on symptoms was observed. The incidence and severity of adverse effects was also recorded.. Thirty-five courses were given to 17 patients. DMSA significantly (P < 0.0001) increased urine lead excretion and significantly (P < 0.0001) reduced blood lead concentrations. Mean daily urine lead excretion exceeded the pre-treatment value by a median of 12-fold with wide variation in response (IQR 8.9-14.8, 95% CI 10.1-14.6). Pre-treatment blood lead concentrations correlated well with 5-day urine lead excretion. Headache, lethargy and constipation improved or resolved in over half the patients within the first 2 days of chelation. DMSA was generally well tolerated, but one course was discontinued due to a severe mucocutaneous reaction. There was a transient increase in alanine aminotransferase (ALT) activity during 14% of chelations. DMSA caused a significant increase in urine copper (P < 0.0001) and zinc (P < 0.05) excretion.. Oral DMSA 30 mg/kg/day is an effective antidote for lead poisoning, though there is a wide inter- and intra-individual variation in response.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antidotes; Chelating Agents; Chelation Therapy; Drug Evaluation; Female; Humans; Lead; Lead Poisoning; Male; Middle Aged; Succimer; Young Adult

Seventeen East-European workers with a suspected lead-intoxication presented themselves to the Department of Toxicology. All of them had worked on the renovation of pylons of a high-tension line. The old paint, known to contain lead was removed with needle descalers. The patients had blood lead concentrations between 325 and 1124 microg/l, but no specific symptoms. The workers neglected the protective measures at their working-place.. 12 of 17 workers had lead-concentrations above 400 microg/l (Reference < 90 microg/l). 10 of 17 patients showed an increased level of free protoporphyrins and all workers showed a decreased activity of delta-aminolaevulinacid-dehydratase (ALAD).. Patients with lead-concentration above 700 microg/l were treated with the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA) 3 x 200 mg/d for nine days. The patients with lead concentrations between 400 and 700 microg/l were treated which DMSA 3 x 100 mg/d. After the DMSA-treatment the lead-concentrations had dropped (p < 0.001). During the DMSA-therapy one patient had to be treated in the hospital because of a generalised allergic exanthema.. We report seventeen patients with high lead concentration in their blood due to occupational exposure. The high blood lead levels showed that the workers had not been protected adequately. This examplifies that occupational lead exposure still occurs, also in Germany. By patients with unspecific symptoms connected with lead exposure a biomonitoring for lead is necessary.

Topics: Antidotes; Chelating Agents; Germany; Humans; Kinetics; Lead; Lead Poisoning; Occupational Diseases; Occupational Exposure; Pain; Porphobilinogen Synthase; Succimer

Lead poisoning from novel environmental sources continues to present a challenge to clinicians who treat infants and children.. A 12 month old infant of Thai parents was found during well child care to have a venous blood lead concentration of 61 mcg/dL. He was hospitalized for parenteral chelation with CaNa2EDTA and subsequently managed as an outpatient with oral succimer, with a reduction in blood lead concentration to 23 mcg/dL. Chronic lead poisoning was attributed to the use of a Thai tongue powder by the parents for the first seven months of the infant's life. This ethnic remedy was applied to the tongue to absorb toxins, reduce white patches present after milk feedings, and preserve the infant's health.. Lead contaminated the powder at 109,000 ppm as measured by x-ray fluorescence spectrometry. Two poison centers in Thailand were contacted and initiated a public health inquiry with the Thai Food & Drug Administration (Thai FDA) to remove contaminated products from the marketplace. Their investigation found six additional contaminated tongue powders (of 10 tested) in a Bangkok shop offering Chinese remedies, some with lead levels > 9000 ppm. These products, unregistered with the Thai FDA, were confiscated and the shop closed. Local media attention and case-finding activities of health officials identified one additional infant suffering from lead poisoning due to tongue powders.. Asian tongue powders can be a source of lead poisoning. Medical toxicologists, poison centers, and public health agencies can work together internationally to accomplish effective post-marketing product surveillance.

Topics: Chelating Agents; Drug Contamination; Edetic Acid; Fluorescence; Humans; Infant; Lead; Lead Poisoning; Male; Medicine, East Asian Traditional; Plant Preparations; Spectrometry, X-Ray Emission; Succimer; Thailand; Tongue

Topics: Adult; Anemia; Chelating Agents; Diagnosis, Differential; Foreign Bodies; Humans; Lead Poisoning; Male; Nurse Practitioners; Risk Factors; Severity of Illness Index; Shoulder Injuries; Shoulder Pain; Succimer; Wounds, Gunshot

The aim of this study was to explore the therapeutic efficacies of combined use of meso-2,3-dimercaptosuccinic acid (DMSA) with calcium and ascorbic acid in the treatment of mild to moderately lead-intoxicated mice. Female albino mice were exposed to lead by drinking water contaminated with 0.1% (moderate lead exposure) or 0.05% (mild lead exposure) lead acetate. After the cessation of lead exposure, mice were supplemented by gavage with saline solution, 50 mg/kg body weight (b.w) DMSA, 100 mg/kg b.w DMSA, calcium and ascorbic acid, or 50 mg/kg b.w DMSA and calcium as well as ascorbic acid, respectively. Atomic absorption spectrophotometric method was used to analyze lead levels in blood, bone, liver, kidney and brain. Activities of blood delta-aminolevulinic acid dehydratase (ALAD) were determined by colorimetric method. DMSA supplemented alone could reduce lead levels in both soft tissues and bone and reverse lead-inhibited activities of blood ALAD in mild to moderately lead-intoxicated mice. On the other hand, combined use of DMSA with calcium and ascorbic acid achieved better therapeutic efficacies in mobilizing lead in blood, liver and kidney, and reversing lead-inhibited activities of blood ALAD in moderately lead intoxicated mice than DMSA supplemented alone. Moreover, the better therapeutic efficacies were also found in mildly lead intoxicated mice in mobilizing lead in blood and bone achieved by combined use of DMSA with calcium and ascorbic acid. Combined use of DMSA with calcium and ascorbic acid seems to be the better choice in the treatment of mild to moderate lead-intoxication.

Topics: Animals; Ascorbic Acid; Calcium; Drug Therapy, Combination; Female; Lead; Lead Poisoning; Mice; Porphobilinogen Synthase; Severity of Illness Index; Succimer; Vitamins

The objective of this study was to explore the optimum combination of micronutrients used with 2,3-dimercaptosuccinic acid (DMSA) in the treatment of moderately lead-intoxicated mice. Experiment was carried out based on the orthogonal design L(8)(2(7)) setting six factors with two different levels of each, and eight groups of mice were needed. Mice were exposed to lead by drinking water contaminated with 0.1% lead acetate for four consecutive weeks, and then supplemented by gavage with different combinations of micronutrients with and without DMSA as designed in the orthogonal table. Lead levels in blood, liver, kidney, brain and bone and activities of blood delta-aminolevulinic acid dehydratase (ALAD) were analyzed after cessation of supplementation. The results suggested that DMSA was the only factor which could decrease significantly lead levels in blood, liver, kidney and bone; calcium and ascorbic acid were the notable factors decreasing lead levels in blood, liver, kidney, bone and brain; zinc and calcium were the notable factors reversing the lead-inhibited activities of blood ALAD; taurine was the notable factor decreasing lead levels in kidney and brain; and thiamine was the notable factor decreasing lead levels in brain. The lowest lead level in blood, liver, kidney and bone was shown in the mice supplemented with combination of calcium and ascorbic acid along with DMSA. In conclusion, the optimum combination of micronutrients used with DMSA suggested in present study was calcium and ascorbic acid, which seemed to potentiate the chelating efficacy of DMSA in the treatment of moderately lead intoxicated mice.

Topics: 5-Aminolevulinate Synthetase; Analysis of Variance; Animals; Bone and Bones; Chelating Agents; Female; Indicators and Reagents; Lead Poisoning; Metals; Mice; Micronutrients; Succimer; Tissue Distribution

Topics: Chelating Agents; Child, Preschool; Constipation; Diagnosis, Differential; Humans; Lead Poisoning; Male; Succimer

Topics: Chelating Agents; Chemical and Drug Induced Liver Injury; Child, Preschool; Constipation; Diagnosis, Differential; Humans; Lead Poisoning; Male; Succimer

There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb-exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure.. The present study was designed to answer these questions, using a rodent model of early childhood Pb exposure and treatment with succimer, a widely used chelating agent for the treatment of Pb poisoning.. Pb exposure produced lasting impairments in learning, attention, inhibitory control, and arousal regulation, paralleling the areas of dysfunction seen in Pb-exposed children. Succimer treatment of the Pb-exposed rats significantly improved learning, attention, and arousal regulation, although the efficacy of the treatment varied as a function of the Pb exposure level and the specific functional deficit. In contrast, succimer treatment of rats not previously exposed to Pb produced lasting and pervasive cognitive and affective dysfunction comparable in magnitude to that produced by the higher Pb exposure regimen.. These are the first data, to our knowledge, to show that treatment with any chelating agent can alleviate cognitive deficits due to Pb exposure. These findings suggest that it may be possible to identify a succimer treatment protocol that improves cognitive outcomes in Pb-exposed children. However, they also suggest that succimer treatment should be strongly discouraged for children who do not have elevated tissue levels of Pb or other heavy metals.

Topics: Animals; Arousal; Attention; Chelating Agents; Chelation Therapy; Cognition Disorders; Female; Lead Poisoning; Learning; Rats; Rats, Long-Evans; Succimer; Toxicity Tests

A case of massive lead poisoning from juice contained in a Greek earthenware jug as well as six satellite cases of high lead exposure of similar origin is reported. The intoxicated patient was successfully treated with dimercaptosuccinic acid. Ceramic producers should adhere to the longstanding European legislation.

Topics: Adult; Ceramics; Europe; Female; Humans; Lead Poisoning; Succimer

In one study of children in 27 families with maternal retardation, those children with higher intelligence quotient (IQ) were more likely to have multiple behavior problems than those with lower IQ. If true, this result would affect clinical practice, but it has not been replicated. Because the setting of the initial observation is similar to the setting of childhood lead poisoning, we attempted a replication using data from the Treatment of Lead-Exposed Children (TLC) study, in which 780 children aged 12-33 mo with blood lead levels 20-44 microg/dL were randomized to either succimer treatment or placebo and then followed up to 5 y. Of 656 mothers of TLC children with IQ measured, 113 demonstrated mental retardation (IQ <70). Whether maternal IQ was <70 or >or=70, children with IQ >or=85 were rated more favorably on cognitive tests and behavioral questionnaires than children with IQ <85; these measures included Conners' Parent Rating Scale-Revised at age 5, the Developmental Neuropsychological Assessment at ages 5 and 7, and the Behavioral Assessment System for Children at age 7. Among children of mothers with IQ <70, those with IQ >or=85 did not show more severe clinical behavioral problems, nor were they more likely to show multiple behavior problems. Children with higher IQ have fewer behavior problems, irrespective of the mother's IQ. In the special setting of mothers with IQ <70, children with higher IQ are not at greater risk of behavior problems.

Topics: Achievement; Chelating Agents; Child; Child Behavior Disorders; Child, Preschool; Female; Humans; Intellectual Disability; Intelligence; Intelligence Tests; Lead; Lead Poisoning; Male; Mothers; Neuropsychological Tests; Random Allocation; Social Environment; Succimer; Urban Population

Among divalent cations, the ionophore monensin shows high activity and selectivity for the transport of lead ions (Pb2+) across phospholipid membranes. When coadministered to rats that were receiving meso-dimercaptosuccinate for treatment of Pb intoxication, monensin significantly increased the amount of Pb removed from femur, brain, and heart. It showed a tendency to increase Pb removal from liver and kidney but had no effect of this type in skeletal muscle. Tissue levels of several physiologic (calcium, cobalt, copper, iron, magnesium, manganese, molybdenum, zinc) and nonphysiologic (arsenic, cadmium, chromium, nickel, strontium) elements were also determined after the application of these compounds. Among the physiologic elements, a number of significant changes were seen, including both rising and falling values. The size of these changes was typically around 20% compared with control values, with the largest examples seen in femur. These changes often tended to reverse those of similar size that had occurred during Pb administration. Among the nonphysiologic elements, which were present in trace amounts, the changes were smaller in number but larger in size. None of these changes appears likely to be significant in terms of toxicity, and there were no signs of overt toxicity under any of the conditions employed. Monensin may act by cotransporting Pb2+ and OH- ions out of cells, in exchange for external sodium ions. The net effect would be to shuttle intracellular Pb2+ to extracellular dimercaptosuccinic acid thereby enhancing its effectiveness. Thus, monensin may be useful for the treatment of Pb intoxication when applied in combination with hydrophilic Pb2+ chelators.

Topics: Animals; Drug Synergism; Lead Poisoning; Male; Monensin; Rats; Rats, Sprague-Dawley; Succimer

This study was designed to investigate the therapeutic potential of meso 2,3-dimercaptosuccinic acid (DMSA) and one of its monoesters, monoisoamyl DMSA (MiADMSA), individually or when administered in combination with an extract of Centella asiatica against experimental lead intoxication in rats. Biochemical variables indicative of alterations in the central nervous system and haem biosynthesis were investigated to determine the toxicity in male Wistar rats. Thirty five rats were exposed to 0.2% lead acetate for 10 weeks, followed by 10 days of treatment with DMSA and MiADMSA (50 mg kg(-1), i.p., once daily) alone and in combination with C. asiatica (200 mg kg(-1), p.o., once daily). Biochemical variables indicative of oxidative stress and brain biogenic amines, along with lead concentration in blood and brain, were measured. Lead exposure caused a significant depletion of blood and brain delta-aminolevulinic acid dehydratase (ALAD) activity, an important enzyme of the haem biosynthesis pathway, and glutathione (GSH) level. These changes were accompanied by a marked increase in reactive oxygen species (ROS) level, thiobarbituric acid reactive substances (TBARS), delta-aminolevulinic acid synthase (ALAS) and oxidized glutathione (GSSG) activity in blood and brain. Significant depletion of brain noradrenaline (norepinephrine, NE), 5-hydroxytryptamine (5-HT), dopamine (DA) and acetylcholinesterase (AChE) also were observed following lead exposure. Also seen was a significant depletion in brain glutathione peroxidase (GPx), glutathione S-transferase (GST) and monoamine oxidase activity, as well as blood and brain superoxide dismutase (SOD) activity. These biochemical changes were correlated with an increased uptake of lead in blood and brain. Combined administration of MiADMSA and C. asiatica was most effective in reducing these alterations, including biogenic amines, besides reducing body lead burden, compared with individual treatment with MiADMSA. Certain other biochemical variables responded favourably to combination therapy and monotherapy with MiADMSA. Thus, supplementation of C. asiatica during chelation could be recommended for achieving optimum effects of chelation therapy.

Topics: Animals; Biogenic Amines; Brain; Centella; Chelating Agents; Drug Therapy, Combination; Heme; Lead Poisoning; Male; Plant Extracts; Rats; Rats, Wistar; Succimer

The clinical presentation of lead intoxication may vary widely and in the absence of a high clinical index of suspicion, the diagnosis may be missed. The effects of lead on mitochondrial oxidative phosphorylation and its interaction with calcium-mediated processes explain the heterogenous presentation. In this case report, the diagnosis was finally made when bilateral wrist drop developed on top of abdominal cramps and anemia. Before, ascites raised the suspicion of a tumor. Therefore, each element of the triad of unexplained anemia, abdominal cramps, and bilateral wrist (or foot) drop should lead any physician to consider the diagnosis of lead intoxication. This case also illustrates the importance of a careful and meticulous social history in patient management.

Topics: Abdominal Neoplasms; Chelating Agents; Diagnosis, Differential; Female; Flowers; Hobbies; Humans; Lead Poisoning; Lead Poisoning, Nervous System; Middle Aged; Protoporphyrins; Succimer; Treatment Outcome

From 2003 to 2005, deaths of 3 individuals as a result of cardiac arrest caused by hypocalcemia during chelation therapy were reported to the Centers for Disease Control and Prevention. Two were children, both of whom were treated with edetate disodium. At the time of this writing, the adult case was still under investigation. No previous cases of death resulting from hypocalcemia during chelation have been reported. From our experience and review of the literature, we suggest that health care providers who are unfamiliar with chelation consult an expert before undertaking treatment and that hospital formularies evaluate whether stocking edetate disodium is necessary, given the risk for hypocalcemia and the availability of less toxic alternatives.

Topics: Autistic Disorder; Calcium; Chelating Agents; Chelation Therapy; Child, Preschool; Death, Sudden, Cardiac; Drug Therapy, Combination; Edetic Acid; Fatal Outcome; Female; Humans; Hypocalcemia; Hypoxia-Ischemia, Brain; Infusions, Intravenous; Lead Poisoning; Male; Medication Errors; Middle Aged; Naturopathy; Risk Management; Sodium; Succimer

Topics: Cheek; Chelation Therapy; Child, Preschool; Dimercaprol; Drug Therapy, Combination; Edema; Edetic Acid; Environmental Exposure; Foreign Bodies; Humans; Lead; Lead Poisoning; Male; Pica; Play and Playthings; Protoporphyrins; Seizures; Self-Injurious Behavior; Succimer; Wounds, Gunshot

Lead poisoning is rare. Intake of lead shots may cause damage of the bone marrow, the nervous system, the liver, the kidneys and the endocrine organs.. We present two patients who had taken approximately 120 grams of lead shots. They developed asthenia, nausea and abdominal pain. We tried to remove the lead shots with fluids, laxatives and colonoscopy, but ultimately surgical intervention had to be performed. The patients were also treated with dimercaptosuccinic acid (DMSA).. Although DMSA treatment is associated with a significant decrease in blood lead concentration and an increase of lead urinary excretion, surgical intervention is the most efficient way of treating oral intake of lead. Treatment with DMSA will probably have to go on for months in order to give an additional effect.

Topics: Adult; Antidotes; Foreign Bodies; Humans; Lead Poisoning; Male; Middle Aged; Succimer

Oxidative stress with subsequent lipid peroxidation has been postulated as one mechanism for lead toxicity. Hence in assessing the protective effects of lipoic acid (LA) and meso 2,3-dimercaptosuccinic acid (DMSA) on lead toxicity, they were tested either separately or in combination for their effects on selected indices of hepatic oxidative stress. Elevated levels of lipid peroxides were accompanied by altered antioxidant defense systems. Lead acetate (Pb - 0.2%) was administered in drinking water for five weeks to induce toxicity. LA (25 mg kg(-1) body wt. day(-1) i.p) and DMSA (20 mg kg(-1) body wt. day(-1) i.p) were administered individually and also in combination during the sixth week. Lead damage to the liver was evident in the decreases in hepatic enzymes alanine transaminase (-38%), aspartate transaminase (-42%) and alkaline phosphatase (-43%); increases in lipid peroxidation (+38%); decreases in the antioxidant enzymes catalase (-45%), superoxide dismutase (-40%), glutathione peroxidase (-46%) and decreases in glutathione (-43%) and decreases in glutathione metabolizing enzymes, glutathione reductase (-59%), glucose-6-phosphate dehydrogenase (-27%) and glutathione-S-transferase (-42%). In combination LA and DMSA completely ameliorated the lead induced oxidative damage. Either compound alone was however only partially protective against lead damage.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Antidotes; Aspartate Aminotransferases; Catalase; Lead Poisoning; Lipid Peroxidation; Liver; Male; Rats; Rats, Wistar; Succimer; Superoxide Dismutase; Thioctic Acid

Although many studies have demonstrated the efficacy of succimer chelation in reducing blood and brain lead levels, the relative efficacy of the drug in the two tissues is less well understood. This issue is important because blood lead levels after chelation are used clinically to estimate reductions in the brain, the most critical organ in considering lead-induced neurotoxicity. The present study was designed to further investigate this issue, using multiple chelation regimens. Long-Evans rats were exposed to one of three lead exposure regimens from birth until postnatal day 40, followed by treatment with succimer (one or two 3-week regimens) or vehicle. The results indicated that one succimer regimen was significantly superior to vehicle treatment in lowering lead levels in both blood and brain across the entire 8-week follow-up period. Similarly, a second succimer regimen offered significant additional benefit relative to one regimen for both blood and brain across the 4-week follow-up period. However, several findings revealed that succimer-induced reductions in brain lead lagged behind reductions in blood lead and were generally smaller in magnitude. Furthermore, a rebound was detected in blood, but not brain, lead levels after both succimer regimens. Given the results of this study, we urge caution in using blood lead as a surrogate for brain lead levels, particularly during and immediately after chelation treatment when reductions in blood lead levels overestimate reductions in brain lead levels. The present results suggest that, in clinical use, succimer treatment may need to extend beyond the point at which blood lead levels have dropped to an "acceptable" target value in order to effectively reduce brain lead levels and minimize neurotoxicity.

Topics: Animals; Biomarkers; Brain; Chelating Agents; Disease Models, Animal; Endpoint Determination; Female; Forecasting; Lead; Lead Poisoning; Male; Models, Theoretical; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Succimer; Tissue Distribution; Treatment Outcome

The combined therapeutic potentials of lipoic acid and dimercaptosuccinic acid were compared against their sole administrations in restoring the altered lead sensitive indices in urine and isolated renal brush-border preparations. Toxicity was induced in male albino rats (Wistar strain) by administering lead acetate (0.2%) in drinking water for 5 weeks, followed by therapy comprising lipoic acid (25 mg/kg body weight) and dimercaptosuccinic acid (20 mg/kg body weight) solely as well as combined during the 6th week. Changes in kidney weights encountered upon lead administration improved after therapy with lipoic acid and dimercaptosuccinic acid. Renal integrity was assessed by measuring the activities of alkaline phosphatase, acid phosphatase, lactate dehydrogenase, leucine aminopeptidase, N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transferase and beta-glucuronidase in urine along with some urinary constituents (urea, uric acid, creatinine, protein and phosphorous). The effects of lead were also studied on isolated brush-border enzymes (alkaline phosphatase, acid phosphatase, gamma-glutamyl transferase and beta-glucuronidase) that showed a decline upon its administration. Increased activities of urinary enzymes were accompanied by increase in the urinary constituents. Increase in renal lead content was paralleled by a drastic fall in the renal delta-aminolevulinic acid dehydratase and a rise in urinary lead levels. Relative to the administration of lead, the combined therapy showed betterment on the renal integrity with respect to the functional parameters assessed, thereby indicating its efficacy over the monotherapies.

Topics: 5-Aminolevulinate Synthetase; Animals; Antioxidants; Biomarkers; Body Weight; Chelating Agents; Disease Models, Animal; Drug Therapy, Combination; Kidney Cortex; Kidney Diseases; Kidney Tubules; Lead Poisoning; Male; Microvilli; Organ Size; Organometallic Compounds; Rats; Rats, Wistar; Succimer; Thioctic Acid

The present study describes the dose-dependent effect of taurine, an amino acid and a known antioxidant, either alone or in combination with meso 2,3-dimercaptosuccinic acid (DMSA) in the treatment of subchronic lead intoxication in male rats. The effects of these treatments in influencing the lead-induced alterations in haem synthesis, hepatic, renal or brain oxidative stress and lead concentration from soft tissues were investigated. Exposure to lead produced a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity, reduction in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) suggesting an altered haem synthesis pathway. Only DMSA was able to increase the activity of ALAD, while both taurine and DMSA were able to significantly increase GSH level towards normal. Animals treated with taurine significantly reduced the alterations in some of the biochemical parameters indicative of oxidative stress. Thiobarbituric acid reactive substance (TBARS) levels reduced significantly in liver, kidney and red blood cells, while GSH level increased. Activity of superoxide dismutase (SOD) also showed an increase in blood and brain in animals treated with taurine. The data also provided a promising role of taurine during chelation of lead by potentiating the depletion of blood, liver and brain lead compared to DMSA alone. It can thus be concluded from the study that concomitant administration of an antioxidant could play a significant and important role in abating a number of toxic effects of lead when administered along with the thiol chelators.

Topics: Aminolevulinic Acid; Animals; Antioxidants; Brain; Chelating Agents; Drug Therapy, Combination; Erythrocytes; Glutathione; Kidney; Lead Poisoning; Liver; Male; Organometallic Compounds; Oxidative Stress; Protoporphyrins; Rats; Rats, Wistar; Succimer; Superoxide Dismutase; Taurine; Thiobarbituric Acid Reactive Substances

Oxidative stress is considered to be a mechanism involved in lead neurotoxicity. Apoptosis is also thought to relate to lead neurotoxicity. The present study, focused on the hippocampus, was designed to investigate the two possible mechanisms involved in lead neurotoxicity and the potential protective effects of 2,3-dimercaptosuccinic acid (DMSA) and oligomeric procyanidins (OPC). It was proved that reactive oxygen species and oxidative damage were implicated in the induction of apoptosis induced by lead in the hippocampus. Administration of DMSA attenuated the oxidative stress and apoptosis in addition to having strong chelating and lead-removing capacity. OPC alone had antioxidant protective effects in the hippocampus but no removing capacity for lead in vivo despite showing higher affinity and stronger chelating ability for Pb(2+) than DMSA in vitro. It is suggested that OPC chelates Pb(2+) but does not discharge it from the body and even accumulates Pb(2+) in some organs. At the same time, a reasonable deduction can also be made that the complex of OPC-Pb(2+) prevents or at least weakens the neurotoxicity of Pb(2+). Whether this complex displays toxicity over a long time span should be studied further.

Topics: Animals; Anthocyanins; Apoptosis; bcl-2-Associated X Protein; Chelating Agents; Free Radical Scavengers; Free Radicals; Glutathione; Glutathione Reductase; Hippocampus; Lead; Lead Poisoning; Lipid Peroxidation; Male; Neurons; Oxidation-Reduction; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Succimer; Time Factors

The therapeutic efficacy of calcium disodium ethylenediaminetetracetic acid (CaNa(2)EDTA) and the two thiol chelators, 2,3-dimercaptopropane 1-sulfonate (DMPS) and monoisoamyl dimercaptosuccinic acid (MiADMSA) was studied, both individually and in combination, in reducing lead concentration in blood and soft tissues and in restoring lead induced altered biochemical variables in rats. Exposure to subacute dose of lead implicated a critical role of reactive oxygen species (ROS) and oxidative stress in altering the normal values of these variables. Exposure to lead caused a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD), an important enzyme in the haem synthesis pathway and glutathione (GSH) level. These changes were also accompanied by inhibition of ALAD activity in kidney, delta-aminolevulinic acid synthase (ALAS) activities in liver and changes in platelet counts in whole blood suggesting disturbed haem synthesis pathway. Lead exposure also led to a pronounced depletion of brain GSH contents, superoxide dismutase (SOD) activity, an increase in thiobarbituric acid reactive substances (TBARS), and activity of glutathione S-transferase (GST). Specific activities of membrane-bound enzymes, acetylcholinesterase (AChE) and monoamine oxidase (MAO), were significantly inhibited on lead exposure. These biochemical changes were correlated with increased uptake of lead in blood and soft tissues. Post lead exposure treatment with MiADMSA in particular provided significant recovery in altered biochemical variables besides significant depletion of tissue lead burden. Treatment with CaNa(2)EDTA and DMPS individually had only moderate beneficial effects on tissue oxidative stress, although they were equally effective in the removal of tissue lead burden. Tissue zinc and copper levels did not depict any significant depletion, although changes like marked depletion of zinc following CaNa(2)EDTA and copper after MiADMSA administration were of some concern. Combined administration of CaNa(2)EDTA, particularly with MiADMSA, was the most effective treatment protocol compared to all other treatments. It can be concluded from our present results that combined therapy with CaNa(2)EDTA and MiADMSA proved significantly better in restoring biochemical and clinical variables over monotherapy with these chelating agents against subacute lead exposure in adult rats.

Topics: Animals; Brain; Chelating Agents; Drug Therapy, Combination; Edetic Acid; Glutathione; Hemoglobins; Kidney; Lead; Lead Poisoning; Male; Metals; Oxidative Stress; Porphobilinogen Synthase; Protoporphyrins; Rats; Rats, Wistar; Succimer; Unithiol

Lead is a ubiquitous element in the environment causing oxidative burst in the exposed individuals leading to tissue damage. Antioxidants have long been known to reduce the free radical-mediated oxidative stress while, thiol chelators have been used to treat arsenic toxicity. The therapeutic efficacy of melatonin or N-acetylcysteine (NAC) was studied in the present study, both individually and in combination with a potent thiol-chelating agent, meso 2,3-dimercaptosuccinic acid (DMSA), in reducing lead concentration in blood and other soft tissues. Their ability to restore altered haematopoietic, hepatic and other biochemical variables indicative of tissue oxidative stress in male rats was also investigated. Administration of melatonin and NAC individually, provided significant protection to lead induced disturbed antioxidant defense that may significantly compromise normal cellular function. Administration of melatonin and NAC also provided a significant protection to thiobarbituric acid reactive substances (TBARS) levels, reduced glutathione (GSH) and oxidized glutathione (GSSG) contents in tissues, suggesting their ability to act as a free radical scavenger and in protecting cells against toxic insult. NAC, a thiol containing antioxidant, has been used under several clinical conditions with few adverse side effects. It has a high toxicity threshold and its wide therapeutic window enhances its utility. The antioxidant action of NAC is due to its ability to interact with reactive oxygen species (ROS) or its ability to stimulate endogenous glutathione (GSH) synthesis. DMSA, on the other hand when given alone, provided significant recovery in restoring the altered lead sensitive biochemical indices like blood delta-aminolevulinic acid dehydratase (ALAD), urinary delta-aminolevulinic acid (ALA), beside increasing urinary lead excretion and decreasing lead concentration in blood and soft tissues. Interestingly, combined treatment of DMSA and NAC provided more pronounced efficacy in restoring altered biochemical variables and in reducing body lead burden than monotherapy with DMSA. The results thus, suggest the involvement of ROS in lead toxicity and a pronounced beneficial role of NAC in therapeutic implications of lead poisoning when co-administered with a thiol chelator (DMSA) supporting the hypothesis that cellular redox status may be significantly reversed by utilizing a thiol containing antioxidant compound. It can be concluded that, combined therapy wit

Topics: Acetylcysteine; Animals; Antioxidants; Brain; Brain Chemistry; Chelating Agents; Kidney; Lead; Lead Poisoning; Liver; Male; Melatonin; Oxidative Stress; Rats; Succimer

The efficacy of meso-dimercaptosuccinic acid (DMSA) (succimer) in treating avian lead intoxication was studied in a retrospective, nonrandomized, longitudinal study. Nineteen birds with moderate to high blood lead concentration and neurologic signs compatible with lead toxicity were treated with DMSA (30 mg/kg p.o., b.i.d.; n = 15) for a minimum of 7 days. In cases with severe neurologic signs, DMSA was supplemented with a single dose of edetate calcium disodium (<50.0 mg/kg of body weight i.m.; n = 4). Blood lead concentrations were measured two or more times (before and after treatment). Median blood lead concentration decreased (87%), neurologic signs were resolved, and there were no apparent adverse secondary effects.

Topics: Administration, Oral; Animals; Animals, Zoo; Bird Diseases; Birds; Chelating Agents; Lead; Lead Poisoning; Longitudinal Studies; Regression Analysis; Retrospective Studies; Succimer

Ameliorative effects of few naturally occurring antioxidants like ascorbic acid (vitamin C), alpha-tocopherol (vitamin E) either alone or in combination with meso-2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA (MiADMSA), on parameters indicative of oxidative stress in the liver, kidney, brain and blood of lead-exposed rats were studied. Male Wistar rats were exposed to 0.1% lead acetate in drinking water for 3 months and treated thereafter with DMSA or its analogue MiADMSA (50 mg/kg, intraperitoneally), either individually or in combination with vitamin E (5 mg/kg, intramuscularly) or vitamin C (25 mg/kg, orally) once daily for 5 days. The effects of these treatments in influencing the lead-induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from the soft tissues were investigated. Exposure to lead produced a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity from 8.44+/-0.26 in control animals to 1.76+/-0.32 in lead control, reduction in glutathione (GSH) from 3.56+/-0.14 to 2.57+/-0.25 and an increase in zinc protoporphyrin level from 62.0+/-3.9 to 170+/-10.7 in blood, suggesting altered haem synthesis pathway. Both the thiol chelators and the two vitamins were able to increase blood ALAD activity towards normal, however, GSH level responded favorably only to the two thiol chelators. The most prominent effect on blood ALAD activity was, however, observed when MiADMSA was co-administered with vitamin C (7.51+/-0.17). Lead exposure produced a significant depletion of hepatic GSH from 4.59+/-0.78 in control animals to 2.27+/-0.47 in lead controls and catalase activity from 100+/-3.4 to 22.1+/-0.25, while oxidized glutathione (GSSG; 0.34+/-0.05 to 2.05+/-0.25), thiobarbituric acid reactive substance (TBARS; 1.70+/-0.45 to 5.22+/-0.50) and glutathione peroxidase (GPx) levels (3.41+/-0.09 to 6.17+/-0.65) increased significantly, pointing to hepatic oxidative stress. Altered, reduced and oxidized GSH levels showed significant recovery after MiADMSA and DMSA administration while, vitamins E and C were effective in reducing GSSG and TBARS levels and increasing catalase activity. Administration of MiADMSA alone and the combined administration of vitamin C along with DMSA and MiADMSA were most effective in increasing hepatic GSH levels to 4.88+/-0.14, 4.09+/-0.12 and 4.30+/-0.06, respectively. Hepatic catalase also reached near normal level in animals co-administered v

Topics: Animals; Antidotes; Antioxidants; Ascorbic Acid; Chelating Agents; Cysteinyldopa; Disease Models, Animal; Drug Therapy, Combination; Lead Poisoning; Male; Oxidative Stress; Porphobilinogen Synthase; Protoporphyrins; Rats; Rats, Wistar; Succimer; Treatment Outcome; Vitamin E

One of the most intriguing phenomenon observed during lead toxicity has been attributed to lead-induced oxidative stress. The combined effect of DL-alpha-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced alterations in selected parameters, which are indicators of oxidative stress in erythrocytes, have been studied. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce toxicity. LA (25 mg/ kg body weight per day i.p.) and DMSA (20 mg/kg body weight per day i.p.) were administered individually and also in combination during week 6. Clinical evidence of toxic exposure was evident from the elevated blood lead levels (BPb) along with lowered levels of haemoglobin (Hb) and haematocrit (Ht). Lead-exposed animals showed enhanced membrane lipid peroxidation (LPO) in the erythrocytes. Damage to the erythrocyte membrane was evident from the decline in the activities of the transmembrane enzymes, viz., Na+, K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase. Lead-exposed rats also suffered an onslaught on the antioxidant defence system witnessed by lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH). Serum glutamic-oxoloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were also elevated in lead-exposed rats. Treatment with either LA or DMSA reversed the lead-induced biochemical disturbances encountered by the erythrocytes, but combined treatment with LA and DMSA was very effective in mitigating all the parameters indicative of oxidative stress.

Topics: Alanine Transaminase; Animals; Antidotes; Antioxidants; Aspartate Aminotransferases; Erythrocyte Membrane; Lead Poisoning; Lipid Peroxidation; Male; Models, Animal; Oxidative Stress; Rats; Rats, Wistar; Succimer; Thioctic Acid

Our objective is to present a case of symptomatic lead toxicity (plumbism) with abdominal colic and hemolytic anemia following a gunshot wound. It is a retrospective case report and the setting is in a teaching hospital in south central Los Angeles. The case report is that of a patient who presented with abdominal pain, generalized weakness, and hypertension following multiple gunshot wounds, 15 years previously. Other causes of abdominal pain and weakness--such as diabetes mellitus, alcohol abuse, pancreatitis, and substance abuse--were ruled out. Interventions included treatment with the newer oral chelating agent, Succimer (2, 3-dimercaptosuccinic acid), and subsequent surgery. The main outcome was the initial reduction in blood lead levels with improvement of symptoms. Because of a recurrent rise in the blood lead levels, the patient was again treated with Succimer and underwent surgery to remove two bullet fragments from the face. We conclude that lead toxicity should be ruled out in patients presenting with abdominal cramps and a history of a gunshot wound. Prompt therapy--including environmental intervention and chelation therapy--is mandatory, and surgical intervention may be necessary.

Topics: Abdominal Pain; Adult; Anemia, Hemolytic; Chelating Agents; Humans; Lead; Lead Poisoning; Male; Succimer; Time Factors; Wounds, Gunshot

It was suggested that ascorbic acid as a natural chelating agent can influence lead toxicokinetics and improve chelating properties of dimercaptosuccinic acid (DMSA) in adult rats. In this paper potential benefits of ascorbic acid supplementation, alone or combined with DMSA, in decreasing lead retention in suckling rats were evaluated. Such data in young mammals are not available. L-Ascorbic acid (daily dose 650 mg/kg b.wt.) and/or DMSA (daily dose 91 mg/kg b.wt.) were administered orally to suckling Wistar rats either during ongoing 8-day oral lead exposure (as acetate; daily dose 2 mg lead/kg b.wt.) or after 3-day lead exposure (total dose 12 mg lead/kg b.wt.). Lead concentrations were analysed in the carcass (skeleton), liver, kidneys and brain by atomic absorption spectrometry. By ascorbic acid supplementation lead retention was not reduced under either lead exposure condition. Lead concentration was even increased in the carcass. Treatment with DMSA under both exposure conditions significantly reduced lead in all analysed tissues. Combined treatment with ascorbic acid and DMSA during ongoing lead exposure was substantially less effective than DMSA treatment alone, and did not affect DMSA efficacy when administered after lead exposure. It was concluded that ascorbic acid administered either during or after lead exposure in suckling rats has no beneficial effect on either lead retention or DMSA chelation effectiveness.

Topics: Administration, Oral; Animals; Animals, Suckling; Antidotes; Ascorbic Acid; Chelating Agents; Drug Synergism; Drug Therapy, Combination; Female; Lead; Lead Poisoning; Male; Rats; Rats, Wistar; Succimer

Topics: Chelating Agents; Child, Preschool; Environmental Exposure; Female; Humans; Infant; Lead Poisoning; Longitudinal Studies; Male; New Jersey; Outpatient Clinics, Hospital; Randomized Controlled Trials as Topic; Research Subjects; Researcher-Subject Relations; Social Work; Socioeconomic Factors; Succimer; Urban Health

The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-alpha-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p.) and DMSA (20 mg/kg body weight per day i.p.) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of gamma-glutamyl transferase and N-acetyl beta- D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione- S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell.

Topics: Acetylglucosaminidase; Animals; Catalase; Chelating Agents; Disease Models, Animal; Drug Therapy, Combination; gamma-Glutamyltransferase; Glutathione; Glutathione Peroxidase; Kidney; Lead Poisoning; Lipid Peroxidation; Lipid Peroxides; Male; Rats; Rats, Wistar; Succimer; Superoxide Dismutase; Thioctic Acid

Topics: Ambulatory Care; Chelating Agents; Humans; Lead Poisoning; Male; Middle Aged; Succimer

The influence of N-acetyl cysteine (NAC), an antioxidant, on the therapeutic efficacy of meso-2,3-dimercaptosuccinic acid (DMSA), a hydrophilic, and its ester, monoisoamyl 2,3-dimercaptosuccinate (MiADMS), a lipophilic, both soft tissue lead mobilizers, was investigated in lead-preexposed rats. The subsequent treatment of lead-exposed animals with DMSA, MiADMS, or NAC reversed the lead-induced alterations in blood delta-aminolevulinic acid dehydratase, catalase, malondialdehyde (MDA), reduced glutathione, oxidized glutathione, and brain MDA levels. The combined treatment with DMSA and NAC was more effective than that with MiADMS and NAC in enhancing the restoration of all these parameters indicative of lead-induced oxidative stress. These reversals were consistent with the lead-removing ability of DMSA and MiADMS but not that of NAC. As the reversal of these parameters by NAC was independent of its lead-mobilizing capability, this ought to be mainly due to its strong antioxidant property. The increase in blood and brain zinc levels upon lead exposure appears to be the result of the redistribution of endogenous zinc due to lead. Subsequent treatment with DMSA, MiADMS, NAC, or their combination decreased the brain zinc as its excretable complexes with a transient increase in blood zinc level. The ideal treatment of lead poisoning seems to be a combination of a lead chelator and an antioxidant.

Topics: Acetylcysteine; Aminolevulinic Acid; Animals; Antioxidants; Brain; Catalase; Chelating Agents; Free Radical Scavengers; Glutathione; Kidney; Lead; Lead Poisoning; Male; Malondialdehyde; Oxidative Stress; Rats; Succimer

The efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) was evaluated in workers occupationally exposed to lead (Pb; blood level >50 microg/dL). Ten men were given 600 mg of DMSA per orem daily, for five days. Pb concentrations of whole blood and urine were determined throughout therapy. Hematology analyses, blood chemistry, and urinalysis were obtained at the start of the study, at the end of the DMSA treatment, and at 72 hours after the administration of the final dose. DMSA therapy had no influence on hepatic, hematologic, or renal functions and was effective in decreasing the concentration of blood Pb in all the subjects without adverse drug reactions.

Topics: Administration, Oral; Adult; Chelating Agents; Humans; Lead; Lead Poisoning; Male; Occupational Diseases; Succimer; Treatment Outcome

Topics: Chelating Agents; Chelation Therapy; Child; Humans; Lead; Lead Poisoning; Succimer

Early clinical features of lead toxicity are non-specific and an occupational history is particularly valuable. Lead in the body comprises 2% in the blood (t1/2 35 days) and 95% in bone and dentine (t1/2 20-30 years). Blood lead may remain elevated for years after cessation from long exposure, due to redistribution from bone. Blood lead concentration is the most widely used marker for inorganic lead exposure. Zinc protoporphyrin (ZPP) concentration in blood usefully reflects lead exposure over the prior 3 months. Symptomatic patients with blood lead concentration >2.4 micromol l-1 (50 microg dl-1) or in any event >3.8 micromol l-1 (80 microg dl-1) should receive sodium calciumedetate i.v., followed by succimer by mouth for 19 days. Asymptomatic patients with blood lead concentration >2.4 micromol l-1 (50 microg dl-1) may be treated with succimer alone. Sodium calciumedetate should be given with dimercaprol to treat lead encephalopathy.

Topics: Acute Disease; Adult; Chelating Agents; Edetic Acid; Humans; Lead; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

Topics: Chelation Therapy; Colonoscopy; Combined Modality Therapy; Female; Foreign Bodies; Humans; Infant; Intestines; Lead Poisoning; Succimer; Therapeutic Irrigation

Topics: Chelating Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; India; Lead Poisoning; Male; Risk Assessment; Severity of Illness Index; Succimer; Treatment Outcome

Topics: Abdominal Pain; Aged; Chelating Agents; Dementia; Diagnosis, Differential; Humans; Lead Poisoning; Male; Succimer

Topics: Chelating Agents; Chelation Therapy; Child Development; Child, Preschool; Cognition; Cost Savings; Humans; Lead; Lead Poisoning; Primary Prevention; Succimer

Two cats from a single household were examined because of neurologic abnormalities suggestive of central vestibular disease. The owner had been renovating her 150-year-old house for the preceding 3 months, and renovations included chipping and sanding of old paint from windowsills and stair railings. Lead toxicosis was diagnosed on the basis of history and concentrations of lead in blood and urine. Both cats were treated with succimer. Treatment was not associated with any adverse effects, and both cats recovered completely. Ingestion of old paint from house renovations is the most common source of lead exposure in cats. Owners of cats with gastrointestinal tract or neurologic abnormalities should be questioned specifically about house renovations.

Topics: Animals; Anorexia; Cat Diseases; Cats; Chelating Agents; Female; Kidney; Lead; Lead Poisoning; Liver; Seizures; Succimer; Tissue Distribution; Vomiting

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.

Topics: Administration, Oral; Animals; Chelating Agents; Child; Disease Models, Animal; Female; Humans; Intestinal Absorption; Isotopes; Lead; Lead Poisoning; Macaca mulatta; Succimer

Seventy-two female rhesus monkeys were randomly assigned to three lead exposure conditions (none, birth to 1 year, birth to 2 years). In a completely crossed design, the lead-exposed and control monkeys were randomized to placebo or chelation therapy which began at 1 year of age. Dosing was conducted daily beginning on day 8 postpartum. The lead dose levels were adjusted biweekly to gradually elevate the blood lead level of each monkey to a target of 1.69-1.93 micromol/L (35-40 microg/dL). Succimer (or placebo) was administered orally (30 mg/kg/day for 5 days and 20 mg/kg/day for 14 additional days) for a total 19-day treatment regimen. There were two separate chelation regimes at 53 and 65 weeks of age. Succimer therapy in combination with lead abatement reduced blood lead levels significantly faster than lead abatement alone; however, that advantage disappeared once succimer therapy was discontinued. Weight, crown-rump length, and head circumference were measured regularly. Growth in weight, length, and head circumference did not vary significantly as a function of blood lead levels. Succimer chelation therapy did not significantly affect weight, length, or head circumference through 2 years of age.

Topics: Administration, Oral; Animals; Body Height; Body Weight; Chelating Agents; Cross-Over Studies; Environmental Exposure; Female; Lead; Lead Poisoning; Macaca mulatta; Random Allocation; Succimer; Treatment Outcome

A 45-y-o male with a history of schizophrenia was admitted to a local VA psychiatric unit. Five days later, endoscopy due to abdominal pain, gastrointestinal bleeding and blood hemoglobin of 5.6 g/dL revealed bullets in the stomach. On subsequent radiograph, > 50 bullets were visualized in the stomach and intestines. Poison Center recommendations included whole bowel irrigation and a blood lead level. After poor results with gastrointestinal decontamination and a repeat radiograph showing > 100 cartridges, surgical intervention was considered but not performed due to perceived risk of bullet detonation from electrocautery. The blood lead was reported as 391 mcg/dL. Calcium EDTA therapy was initiated, followed by aggressive gastrointestinal decontamination. Four days of whole bowel irrigation facilitated passage of 206 cartridges over the next 10 days. The patient was discharged on a 14-day course of 600 mg Succimer tid to treat the bone lead deposits and blood lead level of 49 mcg/dl. An outpatient visit 6 w later showed the blood lead level had dropped to 24 mcg/dl. Aggressive gastrointestinal decontamination and calcium EDTA and Succimer administration successfully treated an ingestion lead bullets and the resulting lead poisoning.

Topics: Antidotes; Chelating Agents; Colon; Edetic Acid; Foreign Bodies; Gastrointestinal Hemorrhage; Humans; Lead; Lead Poisoning; Male; Middle Aged; Schizophrenia; Succimer; Suicide, Attempted; Therapeutic Irrigation; Treatment Outcome

Lead (Pb)-induced hypertension is characterized by an increase in reactive oxygen species (ROS) and a decrease in nitric oxide (NO). In the present study we evaluated the effect of L-arginine (NO precursor), dimercaptosuccinic acid (DMSA, a chelating agent and ROS scavenger), and the association of L-arginine/DMSA on tissue Pb mobilization and blood pressure levels in plumbism. Tissue Pb levels and blood pressure evolution were evaluated in rats exposed to: 1) Pb (750 ppm, in drinking water, for 70 days), 2) Pb plus water for 30 more days, 3) Pb plus DMSA (50 mg kg(-1) day(-1), p.o.), L-arginine (0.6%, in drinking water), and the combination of L-arginine/DMSA for 30 more days, and 4) their respective matching controls. Pb exposure increased Pb levels in the blood, liver, femur, kidney and aorta. Pb levels in tissues decreased after cessation of Pb administration, except in the aorta. These levels did not reach those observed in nonintoxicated rats. All treatments mobilized Pb from the kidney, femur and liver. Pb mobilization from the aorta was only effective with the L-arginine/DMSA treatment. Blood Pb concentrations in Pb-treated groups were not different from those of the Pb/water group. Pb increased blood pressure starting from the 5th week. L-arginine and DMSA treatments (4th week) and the combination of L-arginine/DMSA (3rd and 4th weeks) decreased blood pressure levels of intoxicated rats. These levels did not reach those of nonintoxicated rats. Treatment with L-arginine/DMSA was more effective than the isolated treatments in mobilizing Pb from tissues and in reducing the blood pressure of intoxicated rats.

Topics: Animals; Aorta; Arginine; Blood Pressure; Chelating Agents; Drug Therapy, Combination; Femur; Hypertension; Kidney; Lead; Lead Poisoning; Liver; Male; Rats; Rats, Wistar; Succimer

Topics: Chelating Agents; Chelation Therapy; Child; Humans; Lead; Lead Poisoning; Penicillamine; Succimer; Unithiol

Topics: Chelating Agents; Chelation Therapy; Child; Child Development; Child, Preschool; Cognition Disorders; Double-Blind Method; Humans; Lead; Lead Poisoning; Neuropsychological Tests; Randomized Controlled Trials as Topic; Succimer

We report the case of a pregnant woman with chronic lead toxicity and a blood lead of 57 microg/dL (2.7 micromol/L) who gave birth to a healthy-appearing neonate with a cord blood lead of 126 microg/dL (6.08 micromol/L). The mother was prescribed a single course of oral succimer late in the third trimester of pregnancy, without any appreciable change in her blood lead. The neonate was initially treated with intramuscular dimercaprol and intravenous edetate calcium disodium. After 3 days, the neonate was then switched to oral 2,3-dimercaptosuccinic acid because the blood lead had declined. The child received two 19-day courses of 2,3-dimercaptosuccinic acid and had a blood lead level of 21.5 microg/dL (1.04 micromol/L) at 5 months of age. Despite extensive investigation, the precise source of the mother's lead toxicity remained undetermined.

Topics: Adult; Chelating Agents; Chelation Therapy; Dimercaprol; Edetic Acid; Female; Fetal Blood; Humans; Infant, Newborn; Lead Poisoning; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Succimer

Succimer is considered to be a safe and effective treatment for lead (Pb) poisoning, since it reduces body Pb levels without an apparent diuresis of other essential elements. However, while existing clinical data indicate that succimer does not significantly increase the excretion of non-target elements, those studies have also reported a wide range of outcomes. Therefore, we investigated whether succimer treatment measurably increased the urinary excretion of essential elements in a primate model of childhood Pb exposure. Infant rhesus monkeys (Macaca mulatta) were exposed to Pb from birth through one year of age, and presented blood Pb levels of approximately 40-50 microg/dL at the start of treatment. Subsequently, they were treated with succimer (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days, n = 15) or vehicle (n = 14) for 19 days. Complete urine samples were collected over the first 5 days of treatment, and were analyzed for levels of calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), nickel (Ni), and zinc (Zn), using trace metal-clean techniques and magnetic sector-ICP-MS. Succimer treatment significantly (p < 0.05) reduced blood Pb levels when compared to the vehicle group over the treatment period, and concomitantly produced a significant >4-fold increase in urinary Pb excretion. Succimer treatment also significantly (p < 0.05, multivariate ANOVA) increased the urinary excretion of essential elements, but only when the cumulative total excretion over treatment days 1-5 for all elements were considered. None of these relative increases reached statistical significance for any particular element x day, although increases in Zn (day 3) excretion were only marginally non-significant (0.1 > p > 0.05). Multivariate analyses of a subset of elements (Cu, Fe, Mn, Zn) similarly indicated no significant effect of succimer treatment overall, although the urinary excretion of Mn was significantly increased on day 3 of treatment. Collectively, these data indicate that succimer does contribute to an increase in the urinary excretion of essential elements, although not significantly for any single element considered here. This may be important in Pb-exposed children, who can possess reduced trace element reserves due to nutritional deficiencies.

Topics: Animals; Animals, Newborn; Disease Models, Animal; Lead; Lead Poisoning; Macaca mulatta; Male; Succimer; Trace Elements

Topics: Arsenic Poisoning; Cadmium Poisoning; Chelating Agents; Humans; Lead Poisoning; Mercury Poisoning; Poisoning; Succimer

Ingestion of elemental lead foreign bodies is felt to have a low risk of clinically significant lead absorption unless gastrointestinal pathology and/or prolonged transit time are present. We present a case of ingestion of a large quantity of small diameter lead shot accompanied by rapid elevation of blood lead levels.. A 5 1/2-year-old previously healthy girl was found eating the pellets from an ankle weight. She vomited and complained of abdominal pain. In the emergency department, she had no complaints and normal vital signs. An abdominal X-ray showed thousands of small, round, metallic density objects in the stomach. Her white blood cell count was 14,700/mm3, and the hemoglobin, mean corpuscular volume, free erythrocyte protoporphyrin, zinc protoporphyrin, biochemistry panel 21, and urinalysis were normal. She had no prior lead level for comparison. Whole-bowel irrigation was begun and she passed over 11 stools with pellets as well as other foreign bodies (erasers, bead, etc.) in the first 24 hours. Pellets were still seen on X-ray the following day so she received a high-fiber diet and bisacodyl tablets 10 mg/d. On hospital day 2, her admission blood lead (drawn 13 hours after ingestion) was reported as 57 microg/dL (2.7 microm/L) and chelation was begun with oral 2,3-dimercaptosuccinic acid 10 mg/kg 3x/d for 5 days, then 2x/d for 14 days. Her peak measured lead level was 79 microg/dL approximately 36 hours after ingestion. She excreted 2,273 microg lead in the urine during her first 24 hours of chelation. Her blood lead dropped to 14.3 microg/dL by the end of chelation. She did not develop any apparent signs of lead poisoning.. Acute elevations of blood lead concentrations may occur rapidly after ingestion of multiple small elemental lead objects.

Topics: Antidotes; Bisacodyl; Child, Preschool; Dietary Fiber; Female; Foreign Bodies; Humans; Lead; Lead Poisoning; Radiography; Stomach; Succimer; Therapeutic Irrigation; Treatment Outcome

To compare efficacy and safety of meso-2,3-dimercaptosuccinic acid (DMSA) and Ca EDTA for treatment of experimentally induced lead toxicosis in cockatiels (Nymphicus hollandicus).. 137 (69 females, 68 males) healthy cockatiels between 6 months and 8 years old.. Lead toxicosis was induced by placing lead shot in the gastrointestinal tract. Treatment with Ca EDTA (40 mg/kg of body weight, IM, q 12 h), DMSA (40 or 80 mg/kg, PO, q 12 h), and sodium sulfate salts (SSS; 0.5 mg/kg, PO, q 48 h) was initiated 4 days after induction of lead toxicosis. Blood lead concentrations were determined, using atomic absorption spectrophotometry. Number of birds surviving and blood lead concentrations were compared among groups.. In Phase II of the study, administration of DMSA and Ca EDTA significantly decreased blood lead concentrations when used alone or in combination in birds with lead toxicosis. Addition of SSS did not result in further decreases in lead concentrations. Eight of 12 (66.7%) birds without lead toxicosis given 80 mg of DMSA/kg did not survive to the end of the study. Lesions related to treatment with chelating agents were not detected during necropsy.. DMSA and Ca EDTA are effective chelating agents in cockatiels. Because DMSA is administered orally, it may be easier than other chelating agents for bird owners to administer at home. However, the narrow margin of safety of DMSA indicates that this agent should be used with caution.

Topics: Animals; Bird Diseases; Body Weight; Chelating Agents; Edetic Acid; Female; Kidney; Lead; Lead Poisoning; Liver; Male; Psittaciformes; Random Allocation; Spectrophotometry, Atomic; Spleen; Succimer; Survival Analysis; Thyroid Gland

To evaluate whether dimercaptosuccinic acid (DMSA) -chelatable lead, an estimate of current bioavailable lead stores, is a better predictor of lead-related symptoms than are other commonly used lead biomarkers.. A total of 95 male lead workers from three lead industries (one secondary lead smelting facility, one polyvinyl chloridestabilizer manufacturing plant, and one lead-acid storage battery factory), and 13 workers without occupational lead exposure recruited from an occupational health institute, were studied. Blood lead, blood zinc protoporphyrin (ZPP), 4 h DMSA-chelatable lead (after oral administration of 10 mg/kg DMSA), urine lead, and urinary delta-aminolevulinic acid levels were evaluated as predictors of 15 lead-related symptoms, assessed by self-administered questionnaire, with linear and logistic regression controlling for covariates. Total symptoms and symptoms in three categories (gastrointestinal, neuromuscular, and general) were evaluated.. The mean (SD) 4 h DMSA-chelatable lead level was 288.7 (167.7) microg, with a range from 32.4 to 789 microg in the 95 lead workers. The mean (SD) in the non-exposed subjects was 23.7 (11.5) microg with a range from 10.5 to 43.5 microg. Blood lead, blood ZPP, and spot urine lead levels ranged from 21.4 to 78.4 microg/dl, 40 to 331 microg/l, and 7.5 to 153.0 micro/l, respectively, in the lead workers, and from 4.0 to 7.2 micro/dl, 27 to 52 microg/l, and 2.9 to 15.5 microg/l in the non-exposed controls, respectively. The overall mean symptom score (SD), derived as the sum of 0 or 1 point for absence or presence of 15 symptoms, of the lead workers was 3.7 (2.0), compared to 1.2 (1.5) for the non-exposed workers. DMSA-chelatable lead was the best predictor of symptom scores in both crude and adjusted analyses, compared with the other biomarkers. Lead workers with DMSA-chelatable lead values greater than the median (260.5 microg) were 6.2 times more likely to have frequent tingling or numbness of the arms or legs and 3.3 times more likely to have muscle pain than subjects with lower chelatable lead values. Three symptoms (tingling or numbness of arm or leg, muscle pain, and feeling irritation at the slightest disturbance) evidenced a dose-dependent relationship with DMSA-chelatable lead levels.. DMSA-chelatable lead was found to be the best predictor of lead-related symptoms, particularly of both total symptom scores and neuromuscular symptoms, than were the other other lead biomarkers.

Topics: Adult; Aminolevulinic Acid; Biomarkers; Case-Control Studies; Chelating Agents; Humans; Korea; Lead; Lead Poisoning; Linear Models; Logistic Models; Male; Occupational Diseases; Odds Ratio; Predictive Value of Tests; Protoporphyrins; Succimer; Surveys and Questionnaires

This report of a case of symptomatic lead poisoning in infancy reinforces the need for continued vigilance in screening and the application of effective therapies to prevent serious physiologic, neurocognitive, and behavioral sequelae. Furthermore, this case illustrates the efficacy of repeated courses of outpatient succimer therapy in limiting a rebound in blood lead concentrations.

Topics: Antidotes; Female; Humans; Infant; Lead Poisoning; Prospective Studies; Succimer

Topics: Adult; Chelating Agents; Combined Modality Therapy; Debridement; Humans; Lead Poisoning; Male; Preoperative Care; Radiography; Succimer; Thoracic Injuries; Wounds, Gunshot

A 47-year-old man with a prior gunshot wound presented with arthritis, constipation, abdominal pain, and weight loss. Arthrocentesis did not reveal the cause of the arthritic complaints, but lead poisoning was suspected and confirmed. We present this case along with a short review of the literature pertaining to this often overlooked and reversible cause of lead poisoning.

Topics: Chelating Agents; Chelation Therapy; Foreign Bodies; Humans; Lead Poisoning; Male; Middle Aged; Succimer; Wounds, Gunshot

Postural balance testing was used as a measure of the effect of therapy on a 9 year old boy with high lead levels. Following therapy with CaEDTA and succimer, the patient's postural sway responses were comparable to a low-lead (< 10 micrograms/dL) comparison group for 3 out of 4 tests which rely relatively less on the higher centers for balance. This improvement in postural balance may be attributable to the combined influence of pharmacologic and age associated maturational effects. This case study provides suggestive evidence that while chelation therapy can reduce PbB levels quickly, it can also modify gross neuromotor function manifested by postural balance characteristics.

Topics: Administration, Oral; Child; Dimercaprol; Drug Administration Schedule; Edetic Acid; Humans; Lead Poisoning; Male; Patient Compliance; Postural Balance; Succimer

A 3-y-old child ingested SUCCIMER capsules to receive a dose of 185 mg dimercaptosuccinic acid/kg body weight. No adverse effects occurred.

Topics: Antidotes; Cathartics; Charcoal; Chelating Agents; Child, Preschool; Female; Humans; Lead; Lead Poisoning; Sorbitol; Succimer

Increasing evidence indicates that early low-level lead (Pb) exposure produces enduring cognitive impairment in children, underscoring the need to develop improved therapeutic intervention. Although chelating agents have been shown to effectively reduce body Pb levels, it is not yet known whether this treatment ameliorates Pb-induced cognitive dysfunction. Clinical research in this area is hampered by the need to rely on reductions in blood Pb levels as the index of treatment efficacy, despite the fact that brain Pb level is the exposure parameter of greatest relevance to neurocognitive outcomes. The present studies were designed to provide information that will aid future research in this area in both human and animal models. The objectives of these studies were (1) to evaluate the efficacy of different doses and durations of succimer (meso-2,3-dimercaptosuccinic acid; DMSA) chelation for reducing brain and blood Pb levels and (2) to determine the extent to which blood Pb can serve as a surrogate of brain Pb following chelation. Long-Evans hooded rats were exposed to Pb from birth until day 31 (Study 1) or day 40 (Study 2) of life, followed by oral treatment with a vehicle or one of two succimer regimens for a duration of either 7 or 21 days. Results indicated that 7 days of succimer treatment produced a 1.5- to 2.5-fold greater reduction of Pb in blood than in brain, relative to time-matched vehicle groups. Prolonged treatment (21) days did not further reduce blood Pb levels (relative to 7-day succimer treatment), but did produce further reductions in brain Pb level compared to time-matched vehicle groups. Thus, chelation-mediated reductions in brain Pb did not parallel reductions in blood Pb over the course of treatment. While the relevance of these data to humans may be confounded by anatomical and physiological differences between rodents and primates, as well as differences in the metabolism of succimer (DMSA), they suggest that clinical studies should exercise caution when using blood Pb as an index of the efficacy of chelation treatment for reducing brain Pb levels.

Topics: Administration, Oral; Animals; Animals, Newborn; Brain; Brain Chemistry; Chelating Agents; Cognition Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Lead; Lead Poisoning; Male; Random Allocation; Rats; Succimer

A seventy-six-year-old patient developed a bulbar form of amyotrophic lateral sclerosis, after chronic lead intoxication from drinking water. Treatment with 2,3 dimercaptosuccinic acid was administered for six months and had no effect on clinical course. We discuss the imputability of lead as a possible etiological factor.

Topics: Aged; Amyotrophic Lateral Sclerosis; Chelating Agents; Female; Humans; Lead Poisoning; Succimer; Treatment Outcome; Water Supply

The aim of this study was to evaluate the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) treatment in workers with increased lead absorption and no overt symptoms of lead poisoning. Seven occupationally lead exposed male workers with blood lead concentrations (PbB) exceeding 50 micrograms/100 ml and a positive calcium disodium ethylenediaminetetraacetate (EDTA) lead mobilization test were treated with DMSA for 19 days. Individual doses were 700 mg DMSA, three times a day from day one to five, and twice a day from day six to 19. The treatment intensified urinary lead excretion, most rapidly during the first five days. The increased elimination was followed by a decline of mean PbB to 15% of the pretreatment values. However, 15 days after the treatment, the PbB concentrations rebounded, yet kept below the baseline values and did not exceed 40 micrograms/100 ml. After repeated EDTA lead mobilization test, urine lead was 23-68% of that before DMSA treatment. It can be concluded that DMSA can effectively reduce chelatable lead in occupationally exposed workers.

Topics: Adult; Chelating Agents; Humans; Lead; Lead Poisoning; Male; Middle Aged; Occupational Exposure; Succimer

Four patients, aged 22-60, belonging to a single family that had been exposed to lead-contaminated food for an unknown period, and nine workers, aged 20-65, who had been exposed to air-borne lead for 6-8 years, were evaluated for lead poisoning in our centres. Blood lead levels were 3.57 +/- 0.39 micromol/L (mean +/- SD) in the family members and 3.46 +/- 0.43 micromol/L (mean +/- SD) in the group of workers. 2,3 dimercaptosuccinic acid (DMSA) therapy was instituted in the four family members while the nine workers were closely monitored after being removed from the contaminated environment without receiving any chelation therapy. DMSA therapy given for the duration of 19 days reduced the blood lead levels to 0.63 +/- 0.44 micromol/L (mean +/- SD), P<0.01, in the four family members. No significant change was observed in the untreated group. The exposure time in the untreated group was probably longer than that in the treated group. Following long-term exposure most of the lead in the body is found in the bones and therefore not easily removed by chelation therapy. No side-effects were reported in the treated group and no rebound elevation of blood lead levels was observed during the therapy period or during the 12-week follow-up period following cessation of therapy. We conclude that 19 days of chelation therapy with DMSA in adults with moderate to severe lead poisoning is effective and safe.

Topics: Administration, Oral; Adult; Aged; Humans; Lead; Lead Poisoning; Middle Aged; Succimer

To compare the response to dimercaptopropanol (BAL) and calcium disodium ethylenediaminetetraacetic acid (EDTA) versus orally administered meso-2,3-dimercaptosuccinic acid (DMSA) and EDTA in children with lead poisoning.. Retrospective review of medical records of children admitted to MetroHealth Medical Center with a whole blood lead (BPb) concentration of 2.17 mumol/L (45 micrograms/dl) or more (or less than 2.17 mumol/L and not a candidate for outpatient oral chelation) and treated with BAL + EDTA or DMSA + EDTA. In each group, the mean BPb values at the end of therapy and at 14 and 33 days after chelation were compared with pretreatment BPb by the Wilcoxon signed-rank test, whereas the Mann-Whitney U test was used to compare percentage change from pretreatment at each follow-up day between the two groups.. Twenty-three children received BAL + EDTA and 22 received DMSA + EDTA. The BPb values (mean +/- SD) at the end of therapy and at 14 and 33 days after chelation were significantly lower than pretreatment in both groups (BAL + EDTA: 17 +/- 10, 34 +/- 7, 36 +/- 11 vs 58 +/- 14 micrograms/dl, p < 0.02, 0.01, 0.001, respectively; DMSA + EDTA: 10 +/- 4, 30 +/- 10, 30 +/- 14 vs 50 +/- 10 micrograms/dl, p < 0.01, 0.001, 0.01, respectively). The percentage reduction (mean +/- SD) in BPb from pretreatment at the end of therapy and on days 14 and 33 after chelation did not differ between the groups (BAL + EDTA: -71.2% +/- 19.8%, -40.2% +/- 13.8%, -37.1% +/- 17%; DMSA + EDTA: -79.9% +/- 8.7%, -38.3% +/- 21.6%, -37% +/- 32%; p > 0.20). Elevation of alanine aminotransferase and vomiting during therapy were observed more frequently in the BAL + EDTA group compared with the DMSA + EDTA group.. Treatment with DMSA or BAL combined with EDTA results in a comparable reduction in BPb.

Topics: Alanine Transaminase; Blood Urea Nitrogen; Child; Child, Preschool; Creatinine; Edetic Acid; Female; Hemoglobins; Humans; Lead Poisoning; Male; Retrospective Studies; Succimer; Vomiting

Topics: Chelating Agents; Child; Humans; Lead Poisoning; Succimer; Zinc

To determine whether succimer (meso-2,3-dimercaptosuccinic acid) would be effective in reducing blood lead concentration in dogs with naturally acquired lead poisoning and whether treated dogs would develop clinically important adverse effects.. Prospective case series.. 13 dogs with moderate-to-high blood lead concentrations (39 to 120 micrograms/dl) and clinical signs of lead poisoning.. Dogs were treated with succimer (10 mg/kg of body weight, PO, q 8 h) for 10 days. Blood and urine samples were analyzed for lead concentration before, during, and after treatment with succimer.. Mean blood lead concentrations on days 0, 3, 7, and 20 were 70.6, 32.7, 16.8, and 27.6 micrograms/dl, respectively. Mean blood lead concentrations decreased 53.6, 76.2, and 60.9% from pretreatment value on days 3, 7, and 20, respectively. Mean urine lead concentrations on days 0, 3, 7, and 20 were 70.0, 485.4, 254.3, and 28.3 micrograms/dl, respectively.. In dogs with naturally acquired lead poisoning, succimer administered orally for 10 days effectively reduced blood lead concentrations and eliminated clinical signs of lead poisoning.

Topics: Administration, Oral; Administration, Rectal; Animals; Chelating Agents; Dog Diseases; Dogs; Female; Lead; Lead Poisoning; Male; Prospective Studies; Succimer

Topics: Adult; Chelating Agents; Female; Foreign Bodies; Humans; Knee Injuries; Knee Joint; Lead Poisoning; Radiography; Succimer; Wounds, Gunshot

To investigate the observation that children with pervasive developmental disorders have later and more prolonged lead exposure and are more likely to be reexposed when compared to lead-poisoned children without pervasive developmental disorders.. Retrospective chart review.. A large, urban lead treatment program.. Over a six year period 17 children with pervasive developmental disorders (including autism) were treated. Compared to a randomly selected group of 30 children without pervasive developmental disorders who were treated for plumbism over the sam interval, those with pervasive developmental delay were significantly older at diagnosis (46.5 vs 30.3 months, p = .03) and had a longer period of elevated blood lead levels (39.1 vs 14.1 months, p = .013) during management. Despite close monitoring, state-mandated environmental inspection and prompt lead hazard reduction or alternative housing, 75% of children with pervasive developmental disorders were reexposed to lead during medical management compared with 23% of children without pervasive developmental disorders (p = .001).. 1) lead intoxication among children with pervasive developmental disorders may appear de novo beyond the third year of life and is associated with a high rate of reexposure; 2) the provision of deleaded housing (by current techniques) may not be sufficient to protect these children from repeated lead exposure; 3) these data support recommendations by the Centers for Disease Control that children with developmental delays be closely monitored for the appearance of lead intoxication. This monitoring should continue beyond the third year of life.

Topics: Chelating Agents; Child Development Disorders, Pervasive; Child, Preschool; Environmental Exposure; Humans; Lead Poisoning; Penicillamine; Pica; Recurrence; Retrospective Studies; Succimer

Topics: Body Surface Area; Chelating Agents; Child; Child, Preschool; Humans; Lead; Lead Poisoning; Succimer

Hepatic lipid peroxidation, glutathione and phospholipid contents of homogenate prepared from the liver of lead-intoxicated male rats treated with 0.3 m mol/kg CaNa2EDTA and DMSA for 8 weeks, either alone or in combination, were investigated. A significant increase in hepatic malondialdehyde (MDA) and a reduction in glutathione levels was noticed. While a marginal decrease in phosphatidyl choline (PC) level was noticed, no effect on phospholipid contents was seen. Treatment with all the three chelating agents elicited decrease in PC level. DMSA alone was partially effective in restoring lead-induced altered hepatic glutathione and MDA levels. Combined treatment may have an adverse effects on hepatic tissue and does not seem to produce immediate recoveries in the lead-induced hepatic damage.

Topics: Animals; Chelating Agents; Chelation Therapy; Edetic Acid; Glutathione; Lead Poisoning; Lipid Peroxidation; Liver; Male; Malondialdehyde; Phospholipids; Rats; Succimer

The formation constants of lead chelates of the stereoisomers of 2,3-dimercaptosuccinic acid (DMSA) were determined from potentiometric titrations in the presence of the competing ligand, EDTA. The lead chelates formed at pH 7.4 with the stereoisomers of DMSA are the monomeric complexes PbL and HPbL. Formation of PbL and HPbL at pH 7.4 is independent of total concentrations of lead and DMSA present, and so is the concentration ratio of PbL:HPbL. Lead is completely chelated at pH 7.4 when the total concentration of ligand is equal to or greater than the total concentration of lead present. Lead tends to bind to a greater extent with rac- than with meso-DMSA, and the relative extent increases with an increase in the concentration ratio of ligand to lead and finally reaches a constant value of 45. The binding sites in the chelates, PbL, of the stereoisomers of DMSA are the two thiolate groups and one carboxylate group. rac-DMSA also forms a dimeric complex Pb2L2 in which both carboxylate groups of the ligands participate in binding with lead ions. The formation constants of the lead chelates of rac-DMSA were invariably found to be larger than those of the corresponding of meso-DMSA chelates, because in all the lead chelates of the stereoisomers of DMSA formed in solution, rac-DMSA existed in staggered anti conformations, whereas meso-DMSA preferred a staggered gauche conformation with respect to carboxylate groups in the ligands. The potential of using ZnL2 of rac-DMSA as a therapeutical lead chelator was assessed by considering its lead-mobilizing ability and its ability to deplete endogenous zinc; on this basis it is predicted that ZnL2 of rac-DMSA is a better chelator than meso-DMSA for the treatment of lead poisoning.

Topics: Chelating Agents; Hydrogen-Ion Concentration; Lead; Lead Poisoning; Ligands; Potentiometry; Sodium; Spectrophotometry, Infrared; Stereoisomerism; Succimer

To determine the short-term efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in mild to moderately lead poisoned children.. Medical records of all pediatric patients receiving 19 days of DMSA between June 1991 and May 1993 were reviewed retrospectively. Patients were included if their pretreatment blood lead concentration (BPb) was 1.21 to 2.36 mumol/L (25 to 49 micrograms/dL) and excluded if they: received DMSA through participation in a pharmaceutical company-sponsored drug study; underwent chelation therapy in the previous 28 days; or received another chelating agent concomitantly with DMSA; or if noncompliance was documented. Homes were inspected and abated of major hazards before chelation therapy. BPb and blood zinc protoporphyrin concentration (ZnP) were obtained at baseline. DMSA was administered in a dose approximating 10 mg/kg per dose every 8 hours for 5 days, followed by 10 mg/kg per dose every 12 hours for 14 days. Baseline laboratory studies were repeated weekly while the patients were receiving therapy and for 2 weeks after therapy, then monthly unless chelated again.. Of the 46 children who were treated with DMSA, 18 were excluded from the analysis. In the remaining 28 children, the mean +/- SD pretreatment BPb and ZnP were 1.79 +/- 0.33 mumol/L (37 +/- 6.9 micrograms/dL) and 1.26 +/- 0.64 mumol/L (71 +/- 36.1 micrograms/dL), respectively. The percent reduction (mean +/- SD) in BPb compared with baseline was -43% +/- 20.8%, -26% +/- 16.9%, and -31% +/- 20.2% on mean days 18, 30, and 80, respectively, whereas the changes in ZnP were -12% +/- 21.7%, -20% +/- 18.1%, and -31% +/- 21.9%, respectively. Eighty percent of patients had 20% or more reduction in their pretreatment BPb and/or ZnP after completion of DMSA therapy (95% confidence interval, 61, 92%). No significant adverse effects were observed except for neutropenia (absolute neutrophil count of 0.752 x 10(9)/L) in one patient.. Our findings support the short-term efficacy of DMSA in children with BPb of 2.36 mumol/L (49 micrograms/dL) or less.

Topics: Administration, Oral; Antidotes; Chelating Agents; Child, Preschool; Female; Humans; Lead Poisoning; Male; Retrospective Studies; Succimer; Time Factors; Treatment Outcome

Topics: Chelating Agents; Child; Dimercaprol; Edetic Acid; Humans; Lead Poisoning; Penicillamine; Succimer

We investigated the effect of chelating agent meso-2,3 dimercaptosuccinic acid (DMSA) on indices of "hyperactive" behavior in lead-exposed and control Binghamton Heterogeneous Stock (Het) mice. As expected, 6 weeks of ingestion of 0.5% lead acetate in drinking water reduced immobility in a forced water swim relative to controls. DMSA did not attenuate this behavioral change. In fact, DMSA interacted with lead exposure to increase locomotor activity in the forced water swim. DMSA also apparently excacerbated lead's tendency to reduce immobility. While any generalizations to human populations should be cautioned, these results and others suggest the need for further research.

Topics: Animals; Arousal; Exploratory Behavior; Lead Poisoning; Male; Mice; Motor Activity; Organometallic Compounds; Succimer; Swimming

1. The therapeutic ability of Ca disodium EDTA and meso 2,3-dimercaptosuccinic acid (DMSA) was studied, both individually and when given in combination, in reducing lead concentration in blood and other soft tissues, and in restoring lead induced altered biochemical variables in acute lead intoxicated rats. 2. Combined treatment with the above two chelating agents was more beneficial in reducing blood and hepatic lead compared to treatment with these drugs alone. Kidney lead concentration however, remained high following combined treatment, indicating the possibility of extra renal burden following treatment. 3. Lead sensitive biochemical variables also responded more favourably to combined treatment than treatment with these drugs alone. However, clinical biochemical indices indicate caution regarding the use of this new treatment regimen, and further investigation is required.

Topics: Alanine Transaminase; Alkaline Phosphatase; Aminolevulinic Acid; Animals; Aspartate Aminotransferases; Drug Therapy, Combination; Edetic Acid; Glutathione; Hemoglobins; Kidney; Lead; Lead Poisoning; Liver; Male; Porphobilinogen Synthase; Proteinuria; Rats; Succimer

Asymptomatic lead poisoning remains a serious public health problem in developed and developing countries. Chelation therapy particularly with calcium disodium ethelenediamine tetracetic acid (CaNa2EDTA) is often used therapeutically to reduce the body burden of lead. This chelating drug has serious side effects and drawbacks primarily related to redistribution of lead, nephrotoxicity, and essential metal depletion. The present study was planned to determine the effectiveness of CaNa2EDTA and meso-2,3-dimercaptosuccinic acid (DMSA) used in combination. Both drugs, when administered individually, resulted in significant urinary excretion of lead and lowered the tissue lead burden. Combined treatment with CaNa2EDTA and DMSA elicits an additive response in promoting urinary lead elimination, depleting body lead burden, and restoring altered lead-sensitive biochemical variables. Further, no redistribution of lead to brain or any other soft organ following combined DMSA-CaNa2EDTA treatment was observed indicating a definite advantage of combined therapy over the conventional treatment with CaNa2EDTA or DMSA alone. However, an elevation of serum transaminase activity, creatinine level, and depletion of blood zinc level may limit the usefulness of this combined treatment.

Topics: Alkaline Phosphatase; Animals; Brain Chemistry; Copper; Drug Therapy, Combination; Edetic Acid; Femur; Kidney; Lead; Lead Poisoning; Liver; Male; Rats; Rats, Wistar; Succimer; Transaminases; Zinc

Topics: Adult; Heating; Humans; Lead Poisoning; Male; Occupational Diseases; Succimer

Sodium dimercaptosuccinate (Na-DMS) ip 1 g.kg-1, dimercaptosuccinic acid (DMSA) ig 1 g.kg-1, DMSA ig 1 g.kg-1 with NaHCO3 or Na-citrate ig 3 g.kg-1 was given to mice, separately. It enhanced the excretion of 210Pb in urine about 3.4, 3.8, 3.6, and 2.3 times vs control, respectively within 24 h. It enhanced the excretion of 203Hg in urine about 2.4, 2.3, 3.3, and 2.7 times, respectively within 24 h. Fecal excretion was not significantly elevated vs control. Tissue radioactivities showed a remarkable decrease in the levels of 210Pb and 203Hg in most organs, but DMSA increase the 210Pb content in kidney. The therapeutic effect of ig DMSA was similar to that of ip sodium dimercaptosuccinate.

Topics: Animals; Lead; Lead Poisoning; Male; Mercury; Mercury Poisoning; Mice; Succimer; Tissue Distribution

Because of its favorable side effects profile, the oral chelating agent dimercaptosuccinic acid is often used for treatment of lead intoxication. We report a case of a 45-year-old black male with glucose-6-phosphate dehydrogenase deficiency and a 17 year history of occupational lead exposure who developed hemolysis during treatment with dimercaptosuccinic acid for symptomatic lead intoxication.

Topics: Anemia, Hemolytic; Chelation Therapy; Glucosephosphate Dehydrogenase Deficiency; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

A lead poisoned adult (blood lead level 384 micrograms/dL) had a specific urinary porphyrin profile of elevated porphyrins including coproporphyrin III and 5-carboxylic acid derivatives. A multilinear gradient elution, modified with an ion-pair and a reversed phase column were employed for the separation of the diagnostically important porphyrin isomers. Fluorescence detection enhanced both sensitivity and selectivity. Both compounds were restored to normal levels following two courses of meso 2,3-dimercaptosuccinic acid: 90 mg/kg/d x 5 d at one month intervals. The decrease of clinical symptoms was associated with increase of delta aminolevulinic acid dehydratase from 53 to 230 U/mL blood and hemoglobin from 8.4 to 12.7 g/dL. Blood lead decreased from 384 to 24 micrograms/dL, urine lead from 1286 to 188 micrograms/L and urine coproporphyrin III from 5712 to 25 micrograms/L.

Topics: Administration, Oral; Adult; Chromatography, High Pressure Liquid; Coproporphyrins; Humans; Lead Poisoning; Male; Metallurgy; Occupational Diseases; Occupational Exposure; Porphobilinogen Synthase; Succimer

Topics: Adult; Age Factors; Child; Humans; Lead Poisoning; Succimer

We compared the pharmacokinetics of meso-2,3-dimercaptosuccinic acid (DMSA) in three children with lead poisoning, three adults with lead poisoning, and five healthy adult volunteers. All subjects received DMSA orally. Maximum blood concentration and time to maximum blood concentration of total DMSA concentration were not statistically different among the groups. Unaltered DMSA was detected in the blood of all poisoned patients but in only one of five healthy volunteers. Elimination half-life of total DMSA (parent drug plus oxidized metabolites) was longer in children with lead poisoning (3.0 +/- 0.2 hours) than in adults with lead poisoning (1.9 +/- 0.4 hours) and healthy adults (2.0 +/- 0.2 hours). Renal clearance of total DMSA was greater in healthy adults (77.0 +/- 13.2 ml/min per square meter) than in either adults (24.7 +/- 3.3 ml/min per square meter) or children with lead poisoning (16.6 ml/min per square meter); renal clearance of the metabolites of DMSA was also greater in healthy adults (64.6 +/- 10.1 ml/min per square meter) than in either adults (35.4 +/- 8.4 ml/min per square meter) or children with lead poisoning (19.5 ml/min per square meter). The DMSA appeared to enter the erythrocytes of patients with lead poisoning to a greater extent than in healthy adults. We conclude that renal clearance of DMSA and its metabolites may be impaired and that the distribution of DMSA in children with lead poisoning may be different from that in adults.

Topics: Adult; Age Factors; Case-Control Studies; Child; Child, Preschool; Female; Humans; Lead; Lead Poisoning; Male; Middle Aged; Succimer

Topics: Alanine Transaminase; Aspartate Aminotransferases; Child; Humans; Lead Poisoning; Succimer

Lead poisoning is an unusual complication of gunshot wounds that occurs when retained lead bullet fragments are in contact with body fluids capable of solubilizing lead. The epidemic of violence by gunfire may result in increasing numbers of lead poisoning cases from this exposure. The use of oral chelation for toxicity resulting from this mode of exposure has not been previously discussed. Cases of lead poisoning arising from bullet lead in the synovial cavity of the hip, synovial cavity of the chest, and pleural space are reported. A combination of surgical debridement and chelation therapy with oral succimer produced a satisfactory outcome in all three cases. Oral succimer may be a safe and effective chelation agent for treating lead toxicity in adults with high lead levels secondary to gun shot wounds.

Topics: Adult; Humans; Lead Poisoning; Male; Middle Aged; Succimer; Wounds, Gunshot

The effects of chelating agent treatment with meso-2,3-dimercaptosuccinic acid (DMSA), Na2CaEDTA, Na2ZnEDTA, and Na3ZnDTPA on the organ lead levels of lead-loaded mice have been determined. At 1 mmol/kg/day i.p., all caused reductions in the lead levels of the kidney after four injections, but only Na2CaEDTA produced a significant reduction in brain lead. All chelating agents caused significant reductions in kidney and brain lead levels when administered at a daily dose of 1 mmol/kg/day for eight days, but only DMSA reduced the bone lead level. In animals given 50 mg Pb/kg or 100 mg Pb/kg, the administration of Na2CaEDTA or DMSA at 1 mmol/kg/day x 8 produced significant reductions in kidney, bone and brain lead levels, but DMSA produced greater reductions of bone lead in both groups and of kidney lead in the group given 100 mg Pb/kg. An examination of published data describing the effect of chelating agent treatment on brain lead levels indicates that DMSA produces a reduction in brain lead levels under all conditions examined to date.

Topics: Animals; Bone and Bones; Brain; Brain Chemistry; Chelating Agents; Edetic Acid; Injections, Intraperitoneal; Kidney; Lead; Lead Poisoning; Mice; Pentetic Acid; Spectrophotometry, Atomic; Succimer

To compare the response to oral meso-2,3-dimercaptosuccinic acid (DMSA) treatment in children with an initial blood lead (BPb) concentration less than versus more than 2.17 mumol/L (45 micrograms/dl).. Retrospective cohort study.. Regional referral lead treatment program in an urban children's hospital.. Thirty consecutive children, median age 34 months (range, 5 to 161 months), with an initial BPb concentration 0.97 to 2.90 mumol/L (20 to 60 micrograms/dl) selected for DMSA use. Reasons for DMSA use included BPb concentration > 2.17 mumol/L (11 children), complications with penicillamine therapy (11), chronic renal failure (1), and compassionate use (7). All patients received required environmental hazard reductions before drug administration.. Group 1 (n = 23) had a mean BPb concentration of 1.50 mumol/L (31 micrograms/dl), and group 2 (n = 7) had a mean BPb concentration of 2.41 (51 micrograms/dl). Sixteen patients (70%) in group 1 and five patients (71%) in group 2 had had previous chelation therapy (p value not significant). No significant difference was found in the mean percentage of the reduction of BPb concentration during treatment of group 1 (60%) versus group 2 (58%). The mean BPb concentration in group 1 rebounded to 70% of pretreatment values by mean day 41; the BPb concentration in group 2 rebounded to 69% by day 37 (p value not significant). Prior chelation therapy did not result in a significant difference in either the percentage reduction of BPb concentration or the percentage of rebound BPb.. DMSA is equally effective in acutely lowering BPb concentration in children with BPb concentrations less than and greater than 2.17 mumol/L.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Lead; Lead Poisoning; Male; Retrospective Studies; Succimer; Treatment Outcome

Topics: Chelation Therapy; Humans; Lead; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

Symptomatic lead poisoning with severe hemolytic anemia was observed in a patient with retained shot gun pellets. Surgical resection of the retained pellets and the use of a newer chelating agent, Succimer (2,3-dimercaptosuccinic acid) successfully lowered blood lead level. Hemolytic anemia was associated with deficient erythrocyte pyrimidine 5'-nucleotidase, and lowering of the lead level corrected the deficiency, suggesting that the enzyme deficiency is responsible for the hemolysis associated with lead poisoning. This case illustrates that retained lead pellets from shotgun wounds can cause severe lead poisoning.

Topics: Adult; Anemia, Hemolytic; Humans; Lead Poisoning; Male; Radiography; Succimer; Wounds, Gunshot

Three cases of lead intoxication after the administration of "house specialties" are illustrated. The lead source could be traced to a lead-containing ointment in all three patients. Two of them suffered lead intoxication as a result of topical application to the lips, while the third had ingested the ointment orally. Clinical signs, diagnosis and therapy of lead poisoning are described in the light of the case reports. The patients were treated with various drugs (N-acetylcysteine and the complex chelators D-penicillamine and 2.3-dimercaptosuccinic acid (2.3-DMSA). The therapeutic effects were determined on specific laboratory features in blood and urine. N-acetylcysteine was not absolutely confirming in our case. D-penicillamine was effective, but only after removal of the source of exposure. Because of its known adverse drug reactions, we preferred the oral lead chelator 2.3-DMSA. Treatment with DMSA resulted in a considerable decrease in the blood lead concentration and in increase in urinary lead output. The urinary excretion of aminolevulinic acid and coproporphyrin normalized under DMSA. The treatment was well tolerated and no appreciable side effects were noticed. The literature on metabolism and the characteristic effects of lead intoxication is reviewed and the production, qualities and administration of emplastrum plumbi are described. All three lead-containing ointments are summarized by the characterizing term "house specialties". One wonders whether it is justified that there is still control and registration of such "house specialties" in Switzerland.

Topics: Adult; Aged; Aged, 80 and over; Chelating Agents; Female; Humans; Lead Poisoning; Male; Middle Aged; Nonprescription Drugs; Ointments; Penicillamine; Succimer

Long-term exposure to lead is known to cause a variety of neurotoxic manifestations, including symptoms of depression. Dimercaptosuccinic acid (DMSA), a recently approved oral chelating agent, can diminish the body burden of lead, but few cases of documented clinical improvement following treatment have been reported. We report a case of moderate to severe depression in a long-term lead worker that appeared to respond dramatically to DMSA. This response suggests a possible therapeutic role for DMSA in the treatment of depression in lead-exposed patients.

Topics: Adult; Depression; Humans; Lead Poisoning; Male; Occupational Diseases; Occupational Exposure; Succimer

Published recommendations (1985) for the management of childhood lead poisoning suggest the use of ethylenediaminetetraacetic acid (EDTA) provocation testing and chelation as the mainstay of treatment for blood lead levels between 25 and 55 micrograms/dL. Since 1985 evidence has accumulated indicating that (1) levels of blood lead less than 25 micrograms/dL are detrimental to cognitive development, (2) EDTA provocation testing may result in potentially harmful shifts in the body lead burden, and (3) oral agents such as penicillamine and 2,3-dimercaptosuccinic acid are effective in reducing elevated lead levels. To determine how this evidence impacts on the management of childhood lead poisoning, the authors surveyed the lead poisoning clinics of pediatric departments in the cities estimated by the United States Public Health Service to have the largest number of children affected by lead poisoning. Thirty (70%) of 43 surveys were completed. Respondents indicated that the lowest blood lead level for which they would use a chelating agent to reduce the lead burden was as follows: 50 micrograms/dL (3%), 45 micrograms/dL (3%), 40 micrograms/dL (13%), 35 micrograms/dL (3%), 30 micrograms/dL (27%), 25 micrograms/dL (47%), and 20 micrograms/dL (3%). For all blood lead levels from 20 through 55 micrograms/dL, EDTA was the most frequently recommended chelating agent (chelation and provocation testing). Fifteen percent of responding lead clinics do not use the provocation test under any circumstances. For a child with a negative EDTA provocation test, the percentage of respondents recommending the use of any chelation therapy ranged from 16% for blood lead levels of 25 through 29 micrograms/dL to 66% for levels of 50 through 55 micrograms/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chelating Agents; Child; Clinical Protocols; Drug Utilization; Edetic Acid; Humans; Lead; Lead Poisoning; Penicillamine; Succimer; United States

Topics: Drug Industry; Humans; Lead Poisoning; Orphan Drug Production; Succimer; United States; United States Food and Drug Administration

Male Sprague-Dawley rats were exposed to high-dose (0.5%) lead acetate for periods ranging from 1 to 9 months; then lead exposure was discontinued, and animals were sacrificed after 12 months. Controls were pair-fed. Two additional groups of low-dose (0.01%) and high-dose (0.5%) rats were exposed to lead for 6 months, then lead was discontinued and the rats were treated with three 5-day courses of 0.5% DMSA (dimercaptosuccinic acid) over the next 6 months. Controls were rats exposed to lead for 6 months, then removed from exposure for 6 months without receiving DMSA. Low-dose lead-treated rats showed no significant pathological changes with or without DMSA treatment, but exhibited a significant increase in GFR after DMSA. High-dose lead-treated animals showed no functional or pathological changes when lead exposure was discontinued after 1 month. However, when duration of exposure was 6 or 9 months, GFR was decreased and serum creatinine and urea nitrogen were increased as compared to controls. Tubulointerstitial disease was severe. Administration of DMSA resulted in an improvement in GFR and a decrease in albuminuria, together with a reduction in size and number of nuclear inclusion bodies in proximal tubules. However, tubulointerstitial scarring was only minimally reduced. It may be concluded that, except for brief initial exposure, discontinuation of high-dose lead exposure fails to reverse lead-induced renal damage. Treatment with the chelator, DMSA, improves renal function but has less effect on pathological alterations. As GFR improved after DMSA treatment in both low-dose and high-dose lead-treated rats, irrespective of the degree of pathological alterations, it may be concluded that the DMSA effect is most likely mediated by hemodynamic changes.

Topics: Acetylglucosaminidase; Albuminuria; Animals; Blood Urea Nitrogen; Creatinine; Erythrocyte Membrane; Glomerular Filtration Rate; Glutathione Transferase; Hematocrit; Kidney; Kidney Diseases; Lead; Lead Poisoning; Male; Rats; Rats, Inbred Strains; Silicon; Sodium-Potassium-Exchanging ATPase; Succimer

Topics: Chronic Disease; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

Topics: Administration, Oral; Beverages; Chelation Therapy; Child; Child, Preschool; Dimercaprol; Edetic Acid; Female; Housing; Humans; Infant; Lead; Lead Poisoning; Male; Penicillamine; Succimer; Unithiol

Topics: Child; Child, Preschool; Environmental Exposure; Female; Fluorescence; Humans; Infant; Lead Poisoning; Socioeconomic Factors; Succimer

Topics: Administration, Oral; Child; Child, Preschool; Humans; Lead Poisoning; Succimer

A 54-year-old male with chronic lead poisoning was treated with 2.3-dimercaptosuccinic acid (DMSA). A daily dosage of 30 mg/kg body weight for three days and 20 mg/kg for four days resulted in a decrease of the blood-lead concentration (B-Pb) from 3.7 to 0.7 mumol/l; the total amount of lead excreted in the urine during the first seven 24 hr periods was 75 mumol. After the treatment, B-Pb slowly increased to 3.3 mumol/l. A second treatment was then initiated and resulted in similar changes in B-Pb. However, during the third treatment, the patient developed a mucocutaneous vesicular flare; the eruptions faded after cessation of the chelation therapy, but could be provoked by DMSA doses of 10 mg/kg and above. Despite the small number of treatment courses, the patient showed obvious mental improvement and reported less headache and improved memory. Thus, DMSA is an efficient chelator that results in a rapid, though temporary decrease in B-Pb. Although oral treatment with this chelator may be supervised from the out-patient clinic, careful monitoring for potential side effects is recommended.

Topics: Chelation Therapy; Chronic Disease; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

2,3-dimercaptosuccinic acid (DMSA) mobilizes lead from superficial depots. In comparison with other chelating agents, DMSA has a high therapeutic index and has the additional advantage that it can be administered orally. We have used DMSA for treatment of chronic occupational lead poisoning in a 54-year old male with signs of neurotoxic effects. The treatment resulted in a rapid decrease in the blood-lead concentration, followed by a slow increase after the treatment and subsequent stabilization at a blood-lead level lower than prior to treatment. During the first course of treatment, almost 100 mumols lead was excreted in the urine. As a result of successive courses of treatments, the patient's condition was improved. However, during the third course of treatment, he developed a mucocutaneous rash which faded again after withdrawal of DMSA; this reaction was subsequently provoked by sub-therapeutic doses, and continued treatment was therefore cancelled. Only minor, reversible side effects of DMSA have hitherto been reported, and DMSA must therefore be regarded a promising agent for long-term, out-patient chelation treatment of chronic lead poisoning.

Topics: Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

Topics: Edetic Acid; Humans; Lead Poisoning; Succimer

Topics: Biological Products; Child; Drugs, Investigational; Humans; Hydroxybutyrates; Lead Poisoning; Pharmaceutical Preparations; Succimer; United States; United States Food and Drug Administration

1. Combined chronic lead and arsenic poisoning was diagnosed in a 33-year-old Korean woman following consumption of a Korean herbal medicine prescribed for haemorrhoids. 2. The patient had malaise, severe difficulty walking, arthralgia, oedema and abdominal pain with diarrhoea. 3. Investigation showed anaemia with basophilic stippling, fragmentation and a raised reticulocyte count. 4. Raised blood and urine lead levels and urine arsenic levels were found. 5. Analysis of the herbal medicine revealed a high lead and arsenic content. 6. Treatment with the newer chelating agent 2,3-dimercaptosuccinic acid was successful, with no detectable side-effects.

Topics: Adult; Arsenic Poisoning; Female; Humans; Lead Poisoning; Phytotherapy; Succimer

The ability of zinc to enhance the efficacy of commonly used chelating drugs in lead intoxication and to reduce the resulting zinc imbalance, was investigated in rats. The simultaneous zinc supplementation increased urinary lead elimination by calcium disodium ethylenediaminetetraacetate (Ca disodium EDTA) and 2,3 dimercaptosuccinic acid (DMSA). Combination therapy was also effective in potentiating the depletion of blood, hepatic and renal lead by calcium disodium EDTA and D-penicillamine (DPA), renal lead by DMSA and reversal of inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity by calcium disodium EDTA and DPA. The body zinc status was also maintained as reflected by urinary, blood and tissue levels of zinc.

Topics: Acetates; Acetic Acid; Administration, Oral; Aminolevulinic Acid; Animals; Chelation Therapy; Drug Therapy, Combination; Edetic Acid; Lead; Lead Poisoning; Male; Penicillamine; Porphobilinogen Synthase; Protoporphyrins; Rats; Succimer

2,3-Dimercaptosuccinic acid (DMSA) an investigational chelant structurally similar to dimercaptopropanol (BAL), offers the advantage of not depleting iron stores on which basis it would not seem to form a toxic chelate with iron. We report the case of a man with a formidable body burden of lead (Pb) and depleted iron stores who was given iron intramuscularly during a defined period of long-term retreatment with DMSA. Initiation of retreatment with DMSA, 30 mg/kg/day given orally in three divided doses for the first 7 days markedly enhanced Pb diuresis, entailed a pronounced fall in blood Pb and abolished symptoms of Pb poisoning. Continuation of retreatment with two-thirds the initial DMSA dose for an added 15 days maintained blood Pb at sustained low levels. Iron sorbitol administered intramuscularly during this period in individual doses of 100 mg of elemental iron given 3 days apart to a conservative total of 400 mg produced no untoward effects, suggesting that a toxic chelate between iron and DMSA was not formed. Serum ferritin entered the normal range and there was virtually an immediate significant decrease in erythrocyte protoporphyrin. Together with discernible increases in haemoglobin, haematocrit and MCV, this pointed to enhanced iron utilization. Since iron utilization is curtailed by high concentrations of Pb, the immediacy and magnitude of the post-chelation rebound in blood Pb precluded iron administration at any other stage. From these data, DMSA emerges as a uniquely versatile new chelant. Suitable for long-term administration, it permits the simultaneous parenteral administration of iron during dose-related sustained decreases in blood Pb.

Topics: Adult; Chelating Agents; Ferritins; Humans; Injections, Intramuscular; Iron-Dextran Complex; Kidney; Lead Poisoning; Longitudinal Studies; Male; Occupational Diseases; Porphobilinogen Synthase; Protoporphyrins; Spectrophotometry, Atomic; Succimer; Sulfhydryl Compounds; Time Factors

Topics: Aminolevulinic Acid; Animals; Ascorbic Acid; Lead; Lead Poisoning; Male; Porphobilinogen Synthase; Protoporphyrins; Rats; Succimer; Sulfhydryl Compounds; Thiamine

Efficacy of calcium disodium EDTA, D-penicillamine (DPA), 2,3 dimercaptosuccinic acid (DMSA), and alpha-mercapto-beta-(2-furyl) acrylic acid (MFA) to reduce the body burden of lead and restore the altered biochemical variables in lead or lead + ethanol administered rats was investigated. The investigation was aimed to suggest suitable prophylaxis of lead intoxication prevalent among workers co-exposed to lead and alcohol ingestion. Administration of lead (10 mg/kg, oral, once daily for 8 weeks) produced a significant inhibition in the activity of blood delta-aminolevulinic acid dehydratase (ALAD), elevation in the blood zinc protoporphyrin (ZPP) and urinary elimination of lead and delta-aminolevulinic acid (ALA). Lead contents of blood, liver, kidney and brain were also significantly higher than the normal control. The above changes were more marked in animals co-exposed to lead + ethanol (20% in drinking water) compared to lead alone. All the chelators were effective in increasing the urinary lead elimination, reducing the above biochemical alterations and lead contents of tissues. The order of effectiveness being DMSA greater than Calcium disodium EDTA greater than DPA greater than MFA. However, the protection was more noticeable in animals treated with lead alone than with lead and ethanol.

Topics: Acrylates; Animals; Chelating Agents; Edetic Acid; Ethanol; Lead; Lead Poisoning; Male; Penicillamine; Rats; Succimer; Sulfhydryl Compounds

An increasing number of factors suggest that a reevaluation of the current use of CaNa2EDTA for elevated Pb body burden is advisable and, further, emphasize the need for alternative safe and efficacious chelating agents. One candidate that appears to have potential is meso-2,3-dimercaptosuccinic acid (DMSA). However, little is known about the pattern of Pb mobilization or redistribution produced by this chelator or about its long-term efficacy, issues that were examined in this study. After a 3- to 4-month exposure to 50 ppm of Pb acetate in drinking water, different groups of rats received an i.p. injection of saline or 25 or 50 mg/kg of DMSA once a day for either 1, 2, 3, 4 or 5 days and were sacrificed 24 hr after the final injection. To assess long-term efficacy of the chelator, an additional group of rats received five injections (one per day) of 50 mg/kg of DMSA and were sacrificed 4 months later. Tissue analyses indicated that DMSA mobilized Pb only from soft tissue, with no loss noted from femur and consequently no observable redistribution of Pb. Large decrements in blood, brain and kidney Pb concentrations were noted, with a delayed loss from liver. The effects were not sustained, however, when assessed 4 months later. With respect to redistribution of mobilized Pb to critical organs and magnitude of decline in soft tissue Pb concentration, DMSA appears to be a safe and particularly effective chelator and thus may be a viable alternative to CaNa2EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Chelating Agents; Lead; Lead Poisoning; Rats; Succimer; Sulfhydryl Compounds; Time Factors; Tissue Distribution

Lead poisoning remains one of the hazards of industrialized civilization. CaNa2 EDTA and dimercaprol, the usual therapeutic measures, have many side effects and can be given by parenteral route alone. The authors present a case of chronic lead poisoning caused by ingestion of contaminated flour ground in a primitive flour mill. The diagnosis was confirmed by the CaNa2 EDTA provocative test. Dimercaptosuccinic acid (DMSA) was given orally as a further provocation and resulted in an 11-fold increase in urinary lead excretion. A 5-day course of treatment with DMSA was instituted, during which symptoms abated, urinary lead excretion increased and the blood lead level decreased. No side effects were noticed. There has been no relapse over several months of follow-up. The authors conclude that the oral use of DMSA is effective, safe and convenient both as a provocative test in establishing the diagnosis of lead poisoning and as a therapeutic tool.

Topics: Adult; Bread; Edetic Acid; Food Contamination; Humans; Lead; Lead Poisoning; Male; Succimer; Sulfhydryl Compounds

Topics: Aminolevulinic Acid; Animals; Body Burden; Chelating Agents; Edetic Acid; Lead; Lead Poisoning; Male; Rats; Succimer; Vitamin B Deficiency

2,3-Dimercaptosuccinic acid (DMSA) is an orally effective drug more specific and with a wider therapeutic index than currently available drugs for lead intoxication. Eighteen men with elevated blood lead (BPb) concentrations received either 30, 20, or 10 mg/kg DMSA for 5 days in three divided daily doses. The mean BPb level decreased 72.5%, 58.3%, and 35.5% of the pretreatment values, with a simultaneous elevation in urinary Pb excretion. Clinical symptoms and biochemical indices of lead toxicity also improved. Red blood cell d-aminolevulinic acid dehydratase activity increased, while urinary excretion of d-aminolevulinic acid and coproporphyrin fell. DMSA was well tolerated; the only observed adverse drug reaction was a mild, transient elevation of serum SGPT levels in two subjects. DMSA appears promising and may greatly simplify the treatment of lead intoxication.

Topics: Administration, Oral; Adult; Aminolevulinic Acid; Analysis of Variance; Drug Evaluation; Humans; Lead; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Porphobilinogen Synthase; Random Allocation; Spectrophotometry, Atomic; Succimer; Sulfhydryl Compounds

Topics: Chronic Disease; Humans; Lead Poisoning; Male; Middle Aged; Succimer; Sulfhydryl Compounds; Wine

Topics: Adult; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Penicillamine; Succimer; Sulfhydryl Compounds; Unithiol

2,3-Dimercaptosuccinic acid (D.M.S.), a new orally effective agent for the treatment of heavy-metal intoxication, was administered to five lead-poisoned smelter workers for six days at dosages ranging from 8.4--12.7 mg/kg/day on the first day to 28.1--42.2 mg/kg/day on the last day. Mean blood-lead concentration decreased significantly from an initial value of 97 +/- 6 microgram/dl to 43 +/- 4 microgram/dl on the last day. Urinary lead excretion was significantly raised. D.M.S. was very well tolerated with no signs of toxicity and no effect on urinary zinc, calcium, magnesium, or iron excretion. Urinary copper excretion was significantly increased, but the magnitude of that effect was not clinically important. D.M.S. seems to be safe and effective for the treatment of lead poisoning.

Topics: Administration, Oral; Adult; Chemical Phenomena; Chemistry; Drug Administration Schedule; Drug Evaluation; Edetic Acid; Humans; Injections, Intravenous; Lead; Lead Poisoning; Metallurgy; Middle Aged; Succimer; Sulfhydryl Compounds

Using minimally lead-poisoned rats, we have measured urinary and fecal lead excretion in response to 2,3-dimercaptosuccinic acid (DMS) administered i.p. or p.o. and compared it to that induced by dimercaptopropanol (BAL) (i.p.), EDTA (i.p.), D-penicillamine (p.o. and i.p.) and the combination of BAL and EDTA (i.p.). At doses of 30 mg/kg, parenterally administered DMS was as effective as i.p. BAL and these two drugs were more effective than the other treatment groups. However, p.o. DMS was only 20% less effective and was as effective as i.p. EDTA and the combination of EDTA + BAL i.p. and significantly more effective than D-penicillamine p.o. or i.p. Unlike BAL, most lead excretion in response to DMS was via the urine, undoubtedly reflecting the greater water solubility of DMS. When mice were fed a diet containing both lead and DMS, the drug prevented the accumulation of porphyrins in erythrocytes. Studies with 210Pb indicate that this prophylactic effect is not due to an inhibition of lead absorption but rather to enhanced excretion of lead. The residual tissue distribution of 210 Pb administered simultaneously with DMS was not different form that of 210Pb alone. Since DMS is orally effective and its LD50 is 30 times greater than that of BAL, we expect this compound to be clinically useful in the treatment of lead poisoning.

Topics: Animals; Dimercaprol; Lead; Lead Poisoning; Male; Mice; Rats; Succimer; Sulfhydryl Compounds