Pb Excretion Research Articles

Metal chelators and neurotoxicity: lead, mercury, and arsenic.

This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion.

20-Hydroxyecdysone protects wheat seedlings (Triticum aestivum L.) against lead stress

20-Hydroxyecdysone (20E) is the most abundant phytoecdysteroid (PE) produced by plants, where it represents a protective molecule against insect attack. The aim of the present study was to assess the effects of 20E on the growth, metabolic enzymes and antioxidant systems of wheat seedlings under lead stress induced by Pb(NO3)2 (3 mM). Pre-treatment concentrations (0, 1, 3 and 5 μM) of 20E were applied for two days, then wheat seedlings were transferred for 5 days to a treatment solution containing lead nitrate. When plants were grown without pre-treatment, germination and growth were impaired, while signs of oxidative stress were observed. 20E pre-treatment (3 or 5 μM) was able to efficiently protect seedlings from Pb toxicity by reducing Pb uptake and Pb-induced oxidative stress, as well by enhancing Pb excretion. Thus, 20E pre-treatment maintains normal germination, elongation, biomass, and metabolism in spite of the presence of Pb. Our results show that 20E protects oxidative balance and enhances the anti-oxidative systems, and more specifically the ascorbate-glutathione system. To our knowledge, this study shows for the first time that 20E treatment induces metabolic changes that allow the plants to resist heavy metal stress.

Arsenic and Manganese Alter Lead Deposition in the Rat

Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs. Despite the recognition that metals in a mixture may alter each other's toxicity by affecting deposition, there is dearth of information on their interactions in vivo. In this work, we investigated the effect of As and Mn on Pb tissue deposition, focusing on the kidney, brain, and liver. Wistar rats were treated with eight doses of each single metal, Pb (5mg/Kgbw), As (60mg/L), and Mn 10mg/Kgbw), or the same doses in a triple metal mixture. The kidney, brain, liver, blood, and urine Pb, As, and Mn concentrations were determined by graphite furnace atomic absorption spectrophotometry. The Pb kidney, brain, and liver concentrations in the metal-mixture-treated group were significantly increased compared to the Pb-alone-treated group, being more pronounced in the kidney (5.4-fold), brain (2.5-fold), and liver (1.6-fold). Urinary excretion of Pb in the metal-mixture-treated rats significantly increased compared with the Pb-treated group, although blood Pb concentrations were analogous to the Pb-treated group. Co-treatment with As, Mn, and Pb alters Pb deposition compared to Pb alone treatment, increasing Pb accumulation predominantly in the kidney and brain. Blood Pb levels, unlike urine, do not reflect the increased Pb deposition in the kidney and brain. Taken together, the results suggest that the nephro- and neurotoxicity of "real-life" Pb exposure scenarios should be considered within the context of metal mixture exposures.

Interaction effects of lead on bioavailability and pharmacokinetics of arsenic in the rat

Arsenic (As) and lead (Pb) are common contaminants found in mine waste materials. For an evidence-based risk assessment, it is important to better understand the potential interaction of mixed contaminants; and this interaction study was investigated in an in vivo rat model. Following co-administration of a fixed dose of As(V) as in sodium arsenate and different doses of Pb as lead acetate to Sprague-Dawley rats, blood arsenic concentration and bioavailability decreased. A decrease in As blood concentration when lead was co-administered was observed with increasing lead doses. Pharmacokinetic parameters for As in the blood showed faster absorption and elimination of this metalloid in the presence of Pb. The elimination half-life of As decreased from 67 days in As solo group to 27-30 with doses of Pb. Bioavailability of As was also decreased by 30-43 % in the presence of Pb. Decreased urinary excretion of Pb and tissue accumulation were also observed. It indicates lower absorption of As when co-administered with Pb. A probable explanation for these findings is that As co-administration with Pb could have resulted in the formation of less soluble lead arsenate. However, such an interaction between As and Pb could only explain about one-third of the variation when real mine waste materials containing both of these elements were administered to rats. This suggests that other effects from physical and chemical parameters could contribute to the bioavailability of arsenic in complex real environmental samples.

Faecal Excretion Dynamic during Subacute Oral Exposure to Different Pb Species in Rattus norvegicus

Faecal excretion is a basic means of detoxification upon ingestion of Pb-contaminated feed. In order to determine a time course of Pb elimination after oral exposure to two different forms of this heavy metal (lead acetate vs. phyto-bound Pb), a feeding study was carried out in experimental rats using the Pb phyto-hyperaccumulator Pistia stratiotes as a model diet. The effect of starvation on Pb excretion was further studied in rats that were fed plant material. Twelve Pb doses (7 μg Pb/1 g BW) were administered orally over a 5-week period. Faeces samples were collected 24 and 72 h post-exposure. Inductively coupled plasma optical emission spectrometry and electrothermal absorption spectrometry methods were used for determination of heavy metal concentrations. Up to 53 % of ingested Pb was rapidly eliminated from the exposed rats via faeces within 24 h after exposure. Faecal excretion in exposed rats differed significantly when compared to that of the control group. Fasting before exposure reduced Pb excretion by up to 50 %. Faecal excretions of both examined Pb forms exhibited almost identical patterns. Considerable differences were revealed concerning total excretion levels; lead acetate was excreted in amount greater extent than those of phytobound Pb. Results of our study suggest that Pb forms occurring in the P. stratiotes tissues are absorbed through the gastrointestinal tract to a greater extent than Pb from lead acetate. Therefore, higher portions of ingested Pb can be available for potential accumulation in tissues of exposed subjects.

Protective effects of puerarin on experimental chronic lead nephrotoxicity in immature female rats

Puerarin (PU), a natural flavonoid, has been reported to possess anti-oxidative and anti-inflammatory activities. In the present study, female Sprague-Dawley rats received lead (Pb) nitrate (300mg/L, via drinking water) and/or PU (400mg/kg/day, orally) to investigate the protective effects of PU on Pb-induced renal damage. Renal toxicity was evaluated by detecting urinary proteins excretion as well as levels of serum urea nitrogen and serum creatinine. Ultrastructural observations and real-time quantitative polymerase chain reaction analyses were performed on kidney cortex tissues to identify the mitochondrial damage and quantify gene expression levels of cytochrome oxidase submits (COX-I/II/III), respectively. Renal cell damage was assessed by light microscopic examination. Lipid peroxidation (LPO) levels and antioxidant status in kidney were also evaluated. Animals that received both Pb and PU showed a better renal function than those that received Pb alone, with minor pathological damage. Moreover, PU significantly reduced LPO and markedly restored the enzymatic and non-enzymatic antioxidants levels in kidney of Pb-treated rats, which may be related to its restoring mitochondrial function. Furthermore, PU administration significantly increased urinary Pb excretion and decreased its level in the serum and kidney. In conclusion, these results suggested that PU reduces renal damage induced by chronic Pb administration through its antioxidant properties and chelating ability.

Lead concentration in feces and urine of exposed rats by x‐ray fluorescence and electrothermal atomic absorption spectrometry

Measurements made in feces and urine of Wistar rats exposed to lead acetate (n = 20) in drinking water since the fetal period were compared with those obtained from a control group (n = 20) in order to assess the age influence on Pb excretion. The measurements were made in different collections of rats aging between 1 and 11 months. To determine the Pb content of the samples, total reflection X‐ray fluorescence (TXRF) and electrothermal atomic absorption spectrometry (ETAAS) were used for the urine samples and energy dispersive X‐ray fluorescence (EDXRF) was used for the feces.The results show high concentrations of Pb being eliminated from the organism by urine and feces in contaminated rats. Values vary from (600 ± 140) µg l−1 to (5 460 ± 115) µg l−1 in urine and from (4 500 ± 300) µg g−1 to (11 400 ± 3 300) µg g−1 in dry feces. The control rats show, in general, low lead concentrations or below detection limits. The fecal/urinary ratio was studied. It was shown to be about three to four orders of magnitude and positively correlated with time. It was verified in feces and urine that excretion decreases with the animal age and that this decrease is made by different levels of excretion. The excretions of Pb in urine and in feces are positively correlated.A good agreement was found between the results obtained with TXRF and ETAAS for urine samples. This work also stresses the suitability of these techniques in the study of Pb intoxication. Copyright © 2011 John Wiley & Sons, Ltd.

Natural variation in 210Po and 210Pb activity concentrations in the urine of Finnish population groups

A study to determine activity concentrations of (210)Pb and (210)Po in the urine of certain Finnish population groups was conducted, to investigate the variation in natural background level of urinary excretion. The study participants were divided into three groups mainly based on their diet. The first group comprised recreational fishermen and the second group represented people consuming more reindeer meat than an average Finn, while people using drinking water with very high activity concentrations of (210)Po were selected for the third group. The fourth group was a control group. The mean urinary excretion of (210)Po in groups 1 and 2 was 73 and 100 mBq d(-1), respectively. These values were higher than the value of the control group (20 mBq d(-1)) and the mean values reported in the literature. The mean daily urinary excretion of (210)Pb in groups 1 and 2, 70 and 52 mBq d(-1), was also slightly higher than that in the control group (32 mBq d(-1)). In contrast, the excretion rates of both (210)Po and (210)Pb for the members of group 3 were one to two orders of magnitude higher than those reported in the literature. This was clearly due to the elevated levels of natural radionuclides in their drinking water. The present study demonstrates the importance of possessing good knowledge of the background levels, in order to allow the determination of the additional exposure due, for example, to the malevolent use of radiation.

Protective effect of N-acetylcysteine on experimental chronic lead nephrotoxicity in immature female rats

Oxidative stress plays a key role in lead (Pb)-induced nephrotoxicity. N-acetylcysteine (NAC) is a potent oxygen free radicals scavenger and a metal chelator. In the present study, female Sprague-Dawley rats received PbAc(2) (300 mg/L, via drinking water) and/or NAC (100 mg/kg/day, by intraperitoneal injection) to investigate the protective effect of NAC on Pb-induced renal damage and oxidative stress as well as its mechanism of action. Renal toxicity was evaluated by measuring urinary excretion of total protein, beta(2)-microglobulin, albumin and urinary enzyme markers of tubular necrosis, as well as serum urea nitrogen level. Activities of antioxidant enzymes, contents of glutathione and malondialdehyde in kidney were also measured. Renal cell damage was assessed by electron microscopy. Animals that received both Pb and NAC showed a better renal function than those receiving Pb alone. Lead-induced tubular lesions and mitochondrial damage were markedly reduced in rats that also received NAC. Also, NAC significantly reduced the levels of lipid peroxidation and markedly restored the enzymic and non-enzymatic antioxidants levels in kidney of Pb-treated rats. Moreover, NAC administration significantly increased urinary Pb excretion and decreased its level in the serum and kidney. In conclusion, NAC treatment prevents renal tubular damage induced by chronic Pb administration, most probably through its antioxidant properties and chelating ability.

Pb and Cd Accumulation and Phyto-Excretion by Salt Cedar (Tamarix Smyrnensis Bunge)

The accumulation and excretion of lead (Pb) and cadmium (Cd) by salt cedar (Tamarix smyrnensis Bunge) were investigated in this study. Tamarix smyrnensis plants were exposed to the mixtures of Pb and Cd and high salinity for 10 wk. Subsequently, Pb and Cd uptake was quantified in the shoots and roots of the plants by ICP-AES. In addition, physiological parameters such as biomass production, shoot length, plant appearance, and chlorophyll content were examined. The roots accumulated the highest amount of Pb. Salinity was found to not have an important effect on Pb translocation to the leaves. Cd was translocated into the aerial part in a higher portion than Pb. Cd content in leaves of T. smyrnensis increased with the increasing salinity. The visible toxicity symptoms, if present, were connected only to the high salinity. The excretion of Pb and Cd by salt glands was observed and quantified. T. smyrnensis excreted a significant amount of metals on the leaf surface. This characteristic of salt cedar plants can be viewed as a novel phytoremediation process for the remediation of sites contaminated with heavy metals that we have termed “phyto-excretion.

Evaluation of occupational exposure in a slide bearings factory on the basis of urine and blood sample analyses

The impact of a slide bearings factory on its workers was examined. Urine and blood samples were collected from 42 workers and six people employed in the offices in the same factory (control group). Concentrations of Al, Cu, Pb and Zn in blood and urine samples were measured twice (before and after chelation therapy) by ICP-MS technique using standard addition method. The essential differences in concentrations of elements for workers and control group were evaluated using non-parametric Mann–Whitney U-test. Significant differences between workers and control group were found for Pb in blood and Al in urine samples. The study was also undertaken to indicate correlation between blood and urine element content, workers' ages, their period of work and work section. It was also found that intravenous administration of 1 g of calcium-disodium versanate significantly increased urinary excretion of Pb and Zn, but not Al.

Lead accumulation from non-saline and saline environment by Tamarix smyrnensis Bunge

Tamarix smyrnensis plants were exposed to Pb(NO 3) 2, with and without addition of salt into soil for 10 weeks. Salt as NaCl was added to water for watering in concentrations 0.5% and 3%. Subsequently, lead uptake was quantified in leaves and roots of the plants by ICP-AES spectrometry. In addition, the influence of Pb on photosynthesis and other physiological parameters was also examined by means of biomass production and shoot length determination. Plant appearance was observed also. The influence of Pb presence in the soil on chlorophyll content was examined. In order to quantify the fate of Pb in the plant, metal excretion by salt glands was investigated as well. It was found that the roots were the main accumulation site of Pb in all plants under all treatments irrespective of salt concentration in soil. Low salinity in soil did not affect Pb accumulation in roots but at high salt concentration Pb accumulation decreased. The opposite was observed in the leaves where more Pb was accumulated at high salt concentration in soil. The toxic effect of Pb was visible only in the group treated with Pb without addition of NaCl into water for watering. The visible toxicity symptoms were connected only with high salinity. No excretion of Pb by salt glands was observed.

Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend χ 2 = 6.4, P = 0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male non-smokers (adjusted β = 0.31, P = 0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted β = −0.38, P = 0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of β2-microglobulin ( P = 0.02) and N-acetyl-β- d-glucosaminidase ( P = 0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend χ 2 = 4.3, P = 0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure.

Evidence for concurrent effects of exposure to environmental cadmium and lead on hepatic CYP2A6 phenotype and renal function biomarkers in nonsmokers.

We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 μg/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 μg/g creatinine. Average age and Cd burden of women and men did not differ. Women, however, on average showed a 46% higher urinary Pb excretion (p < 0.001) and lower zinc status, suggested by lower average serum Zn and urinary Zn excretion compared with those in men. Cd-linked nephropathy was detected in both men and women. However, Pb-linked nephropathy was seen only in women, possibly because of higher Pb burden coupled with lower protective factors, notably of Zn (p < 0.001), in women compared with men. In men, Pb burden showed a negative association with CYP2A6 activity (adjusted β= −0.29, p = 0.003), whereas Cd burden showed a positive association with CYP2A6 activity (adjusted β= 0.38, p = 0.001), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. The weaker correlation between Cd burden CYP2A6 activity in women despite similarity in Cd burden between men and women is consistent with opposing effects of Pb and Cd on hepatic CYP2A6 phenotypic expression. A positive correlation between Cd-linked nephropathy (urinary N-acetyl-β-d-glucosaminidase excretion) and CYP2A6 activity in men (r = 0.39, p = 0.002) and women (r = 0.37, p = 0.001) suggests that Cd induction of hepatic CYP2A6 expression and Cd-linked nephropathy occurred simultaneously.

Monensin Mediates a Rapid and Selective Transport of Pb2+: POSSIBLE APPLICATION OF MONENSIN FOR THE TREATMENT OF Pb2+ INTOXICATION

The carboxylic acid ionophore monensin, known as an electroneutral Na(+) ionophore, an anticoccidial agent, and a growth-promoting feed additive in agriculture, is shown to be highly efficient as an ionophore for Pb(2+) and to be highly selective for Pb(2+) compared with other divalent cations. Monensin transports Pb(2+) by an electroneutral mechanism in which the complex PbMonOH is the transporting species. Electrogenic transport via the species PbMon(+) may also be possible. Monensin catalyzed Pb(2+) transport is little affected by Ca(2+), Mg(2+), or K(+) concentrations that are encountered in living systems. Na(+) is inhibitory, but its effectiveness at 100 mm does not exceed approximately 50%. The poor activity of monensin as an ionophore for divalent cations other than Pb(2+) is consistent with the pattern of complex formation constants observed in the mixed solvent 80% methanol/water. This pattern also explains why Ca(2+), Mg(2+), and K(+) are ineffective as inhibitors of Pb(2+) transport, but it does not fully explain the actions of Na(+), where kinetic features of the transport mechanism may also be important. When given to rats at 100 ppm in feed together with Pb(2+) at 100 ppm in drinking water, monensin reduces Pb accumulation in several organs and tissues. It also accelerates the excretion of Pb that was accumulated previously and produces this effect without depleting the organs of zinc or copper. Monensin, used alone or in combination with other agents, may be useful for the treatment of Pb intoxication.

Chronic oral administration of rhamnogalacturonan-II dimer, a pectic polysaccharide, failed to accelerate body lead detoxification after chronic lead exposure in rats.

Lead is a ubiquitous heavy metal and its toxicity remains an important public health issue. In previous work, we reported that ingestion of rhamnogalacturonan-II dimer (dRGII), a pectic polysaccharide, may decrease intestinal absorption and status of Pb in rats. Here, we evaluated the potential detoxifying effect of different doses of dRGII after chronic oral Pb exposure in rats. For this purpose, six groups of ten male Wistar rats weighing 150g were treated as follows: group A received a semi-purified control diet for 6 weeks; groups B, C, D, E and F received the same diet plus 3 mg Pb (as acetate) for 3 weeks. Group B was then killed. Groups C, D, E, and F continued to receive the semi-purified control diet containing 0, 2, 6 or 18g dRGII/kg diet for 3 additional weeks. During the last 5 d, a Pb conventional balance study was performed. Rats were then anaesthetized and tissues were sampled for Pb and essential minerals assay. The results showed that residual Pb in the added dRGII was not available for absorption. However, the added dRGII failed to induce any significant increase in faecal or urinary Pb excretion. Consequently, at the end of the study the intestinal Pb absorption and balance remained unchanged in the animals receiving the different doses of dRGII. In line with this, we showed that dRGII administration was not effective in decreasing tibia or kidney Pb levels in rats. In conclusion, Pb complexed by dRGII in fruits and vegetables and fruit juice is thus mostly unavailable for intestinal absorption. However, the addition of dRGII after chronic Pb exposure does not help Pb detoxification.

DIFFERENCES IN OXIDATIVE STRESS BETWEEN YOUNG CANADA GEESE AND MALLARDS EXPOSED TO LEAD-CONTAMINATED SEDIMENT

Lead (Pb) exposure results in an increase in tissue lipid peroxides and variation in glutathione (GSH) concentrations, which can be related to peroxidative damage of cell membranes in Pb-poisoned animals. Species and individual variation in sensitivity to Pb poisoning among animals may be due to differential resistance to oxidative stress. The effects of oxidative stress caused by Pb exposure (1.7, 414, and 828 µg/g of diet) were compared for the first 6 wk in growing young of two species of waterfowl, Canada geese ( Branta canadensis ) and mallards ( Anas platyrhynchos ), with the first species being possibly more sensitive to Pb poisoning based on previous field and laboratory observations. Blood and liver Pb concentrations increased more in mallards than in geese. This may be explained on the basis of body weight, being 3.2 times higher in geese, and by hepatic metabolism, where GSH S -transferase (GST) activity is 2.9-fold higher in geese and presumably has a role in the binding of Pb to GSH and subsequent biliary excretion. In contrast, mallards showed higher hepatic levels of GSH and activities of GSH peroxidase (GPX) and GSH reductase (GR). Although both species showed a rise in hepatic GSH concentration with Pb exposure, the relationship between increased lipid peroxidation and Pb exposure was only significant in geese. Within treatment groups, hepatic GSH concentrations were inversely related to liver Pb concentrations in both species, which may correspond to the role of GSH in Pb excretion. Hepatic GSH was also inversely related to hepatic lipid peroxidation, but only in mallards and in agreement with the species differences observed in GPX and GR activities. The lower resistance to lipid peroxidation of Canada geese may explain why geese can die in the field from Pb poisoning after ingesting fewer shot than found in the gizzards of mallards and with lower liver Pb concentrations than in mallards.

Oral Succimer Decreases the Gastrointestinal Absorption of Lead in Juvenile Monkeys

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.

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

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.

Cellular distribution of copper, lead and zinc in the grey mangrove, Avicennia marina (Forsk.) Vierh

The distribution and excretion of Cu, Pb and Zn in the root and leaf tissue of the grey mangrove, Avicennia marina was studied using scanning electron microscope (SEM) X-ray microanalysis and atomic absorption spectroscopy. SEM X-ray microanalysis of nutritive root tissue in seedlings dosed with 4 g/l Cu, Pb and Zn revealed accumulation of all metals predominantly in cell walls. The root epidermis provided a major barrier to the transport of Pb only. The endodermal casparian strip was shown to provide a barrier to movement of all three metals into the stele. Washings from mature leaves contained significantly higher amounts of Zn and Cu than control plants after 1 month, suggesting excretion of both metals from the glandular trichomes. In addition, salt crystals exuded from the glands on the adaxial surface of mature leaves were composed of alkaline metals: Zn in Zn-treated plants, and Cu in Cu-treated plants. Leaf tissue in seedlings dosed with 4 g/l Zn showed a decreasing gradient of the metal from xylem tissue, through photosynthetic mesophyll, to hypodermal (water) tissue, with a subsequent increase in concentration in the glandular tissue. A similar gradient was observed across leaf tissue in seedlings dosed with 4 g/l Cu, however, there was no subsequent increase in Cu concentration in glandular tissue. For both metals leaf cell wall metal concentrations were consistently higher than intracellular concentrations.