Restoration of lead-inhibited 5-aminolevulinate dehydratase activity in whole blood by heat, zinc ion, and (or) dithiothreitol.

1980 ◽  
Vol 26 (5) ◽  
pp. 625-628 ◽  
Author(s):  
T Sakai ◽  
S Yanagihara ◽  
K Ushio

Abstract We examined effects of heat, zinc, ion, and dithiothreitol in restoring the activity of lead-inhibited-5-aminolevulinate dehydratase (EC 4.2.1.24). The ratio of non-activated to activated activity produced by dithiothreitol correlated well with blood lead concentration among 35 lead workers. The individual effects of heat, zinc, or dithiothreitol differ from each other in the shift of pH optimum as well as in the extent to which activity is restored. Dual or triple combinations of these agents show additive or complementary restoration of activity. The combination of heat and zinc or zinc and dithiothreitol expands the range of optimum concentration of zinc in restoring activity. Using these combinations of agents, we can expect more accurate evaluation of lead exposure than by measuring only activation of zinc. Although dithiothreitol most powerfully restores activity, it restores not only the activity inhibited by lead exposure but also the activity removed by oxidation of SH-groups in the enzyme molecule.

1980 ◽  
Vol 26 (5) ◽  
pp. 625-628 ◽  
Author(s):  
T Sakai ◽  
S Yanagihara ◽  
K Ushio

Abstract We examined effects of heat, zinc, ion, and dithiothreitol in restoring the activity of lead-inhibited-5-aminolevulinate dehydratase (EC 4.2.1.24). The ratio of non-activated to activated activity produced by dithiothreitol correlated well with blood lead concentration among 35 lead workers. The individual effects of heat, zinc, or dithiothreitol differ from each other in the shift of pH optimum as well as in the extent to which activity is restored. Dual or triple combinations of these agents show additive or complementary restoration of activity. The combination of heat and zinc or zinc and dithiothreitol expands the range of optimum concentration of zinc in restoring activity. Using these combinations of agents, we can expect more accurate evaluation of lead exposure than by measuring only activation of zinc. Although dithiothreitol most powerfully restores activity, it restores not only the activity inhibited by lead exposure but also the activity removed by oxidation of SH-groups in the enzyme molecule.


1979 ◽  
Vol 56 (1) ◽  
pp. 61-69 ◽  
Author(s):  
P. A. Meredith ◽  
M. R. Moore ◽  
A. Goldberg

1. The activity of erythrocyte δ-aminolaevulinic acid (ALA) dehydratase and blood protoporphyrin concentrations have been measured in patients with various anaemias, a group of subjects with known lead exposure and a group of control subjects. Leucocyte ALA synthase was measured in subjects from the last two groups. 2. Erythrocyte ALA dehydratase activity was significantly depressed in the group of lead-exposed subjects and showed a highly significant negative exponential relationship with blood lead concentration. 3. Blood protoporphyrin concentrations were significantly elevated in the group of lead-exposed subjects and patients with iron-deficiency anaemia and showed a significant positive exponential relationship with blood lead concentration. 4. Comparison of the least-squares regression analysis of these relationships and incidence of false positive and false negative results indicates that erythrocyte ALA dehydratase activity is a more accurate measure of environmental and moderate industrial lead exposure than blood protoporphyrin concentrations. 5. The correlations of erythrocyte ALA dehydratase and leucocyte ALA synthase activity, and of blood protoporphyrin concentrations and leucocyte ALA synthase activity, suggest that blood protoporphyrin more accurately reflects haem synthesis than does erythrocyte ALA dehydratase activity.


Author(s):  
Chan-Ching Huang ◽  
Chen-Cheng Yang ◽  
Te-Yu Liu ◽  
Chia-Yen Dai ◽  
Chao-Ling Wang ◽  
...  

Background: Lead inhibits the enzymes in heme biosynthesis, mainly reducing δ-aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of δ-aminolevulinic acid dehydratase activity reduced by lead exposure. Methods: We collected data on 121 lead workers and 117 non-exposed workers when annual health examinations were performed. ALAD activity was determined by the standardized method of the European Community. ALAD G177C (rs1800435) genotyping was conducted using the polymerase chain reaction and restricted fragment length polymorphism (PCR-RFLP) method. In order to find a threshold effect, we used generalized additive models (GAMs) and scatter plots with smoothing curves, in addition to multiple regression methods. Results: There were 229 ALAD1-1 homozygotes and 9 ALAD1-2 heterozygotes identified, and no ALAD2-2 homozygotes. Lead workers had significantly lower ALAD activity than non-exposed workers (41.6 ± 22.1 vs. 63.3 ± 14.0 U/L, p < 0.001). The results of multiple regressions showed that the blood lead level (BLL) was an important factor inversely associated with ALAD activity. The possible threshold of BLL affecting ALAD activity was around 5 μg/dL. Conclusions: ALAD activity was inhibited by blood lead at a possible threshold of 5 μg/dL, which suggests that ALAD activity could be used as an indicator for lead exposure regulation.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Kelsey M. Gleason ◽  
Linda Valeri ◽  
Anuraj H. Shankar ◽  
John F. Obrycki ◽  
Md Omar Sharif Ibne Hasan ◽  
...  

Abstract Background Many children in Bangladesh experience poor nutritional status and environmental lead exposure, both of which are associated with lower scores on neurodevelopmental assessments. Recent studies have suggested that part of lead’s adverse effects on neurodevelopment are caused in part by lead’s effect on growth. New statistical methods are now available to evaluate potential causal pathways in observational studies. This study used a novel statistical method to test the hypothesis that stunting, a measure of linear growth related to poor nutrition, is a mediator and/or an effect modifier of the lead exposure’s adverse effect on cognitive development. Methods Participants were 734 children from a longitudinal birth cohort established in rural Bangladesh to study the health effects of prenatal and early childhood environmental metal exposures. Lead exposure was estimated using umbilical cord blood samples obtained at birth and blood obtained via venipuncture at age 20–40 months. Stunting was determined using the World Health Organization’s standards. Neurodevelopment was assessed at age 20–40 months years using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). We evaluated the effect of lead on stunting and whether the effect of lead on cognitive scores is modified by stunting status in multivariable regression analyses. We then conducted a novel 4-way mediation analysis that allows for exposure-mediator interaction to assess how much of the effect of lead on cognitive scores is explained by the pathway through stunting (mediation) and how much is explained by the interaction between lead and stunt (effect modification). Results Stunting was not a mediator of the effect of lead in our analyses. Results suggested effect modification by stunting. In an area of Bangladesh with lower lead exposures (median umbilical cord blood lead concentration, 1.7 μg/dL), stunting modified the relationship between prenatal blood lead concentrations and cognitive score at age 2–3 years. A 1-unit increase in natural log cord blood lead concentration in the presence of stunting was associated with a 2.1-unit decrease in cognitive scores (β = − 2.10, SE = 0.71, P = 0.003). This interaction was not found in a second study site where lead exposures were higher (median umbilical cord blood lead concentration, 6.1 μg/dL, β = − 0.45, SE = 0.49, P = 0.360). Conclusions We used a novel method of mediation analysis to test whether stunting mediated the adverse effect of prenatal lead exposure on cognitive outcomes in Bangladesh. While we did not find that stunting acted as mediator of lead’s effect on cognitive development, we found significant effect modification by stunting. Our results suggest that children with stunting are more vulnerable to the adverse effects of low-level lead exposure.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Kelsey Gleason ◽  
James P. Shine ◽  
Nadia Shobnam ◽  
Lisa B. Rokoff ◽  
Hafiza Sultana Suchanda ◽  
...  

Background.During the conduct of a cohort study intended to study the associations between mixed metal exposures and child health outcomes, we found that 78% of 309 children aged 20–40 months evaluated in the Munshiganj District of Bangladesh had blood lead concentrations ≥5 µg/dL and 27% had concentrations ≥10 µg/dL.Hypothesis.Environmental sources such as spices (e.g., turmeric, which has already faced recalls in Bangladesh due to high lead levels) may be a potential route of lead exposure.Methods.We conducted visits to the homes of 28 children randomly selected from among high and low blood lead concentration groups. During the visits, we administered a structured questionnaire and obtained soil, dust, rice, and spice samples. We obtained water samples from community water sources, as well as environmental samples from neighborhood businesses.Results.Lead concentrations in many turmeric samples were elevated, with lead concentrations as high as 483 ppm. Analyses showed high bioaccessibility of lead.Conclusions.Contamination of turmeric powder is a potentially important source of lead exposure in this population.


2021 ◽  
Author(s):  
Nonhlanhla Tlotleng ◽  
Nisha Naicker ◽  
Angela Mathee ◽  
Andrew C. Todd ◽  
Palesa Nkomo ◽  
...  

Abstract Background: An association between blood-lead levels and aggression has been demonstrated in children and adolescent youth in South Africa. However, there are limited studies that have assessed aggression as an outcome for cumulative lead exposure using bone-lead concentration. The aim of this study was to assess the association between bone-lead concentration and aggressive behaviour among a sample of the youth in South Africa. Methods: Bone lead in 100 participants (53 males and 47 females) recruited and followed in the Birth to Twenty (BT20) Cohort were measured using 109Cd-based, K-Shell X-ray Fluorescence (KXRF). The Buss-Perry Aggression questionnaire was used to measure aggressive behaviour. Linear regression models were fitted to determine the association between aggression score for physical, verbal, anger and hostility and bone lead, adjusting for known confounders. Results: The study participants were between the ages of 23 and 24 years. A one-microgram-per-gram increase in bone lead was found to increase the score for all four scales of aggression, but significantly only for anger (β=0.2 [95% CI 0.04-0.370]). Psychosocial factors such as a history of family violence and exposure to neighbourhood crime were found to be significant predictors for aggression. Conclusion: The study provides a preliminary overview of the relationship between cumulative lead exposure and behavioural problems such as aggression. A larger sample, across exposed communities, may prove more definitive in deciding whether further investigating this association could maximize generalizability. Such information could be crucial in the drafting of policies designed to combat crime associated with youth aggression in South Africa.


1978 ◽  
Vol 93 (3) ◽  
pp. 476-478 ◽  
Author(s):  
Jacqueline E. Ryu ◽  
Ekhard E. Ziegler ◽  
Samuel J. Fomon

2000 ◽  
Vol 108 (3) ◽  
pp. 275-280 ◽  
Author(s):  
M.A. Arrieta ◽  
S.I. Per� ◽  
C. Apart�n ◽  
C.E. Rosenberg ◽  
N.E. Fink ◽  
...  

1983 ◽  
Vol 15 (S1) ◽  
pp. 17-21
Author(s):  
P V Hodson

The measurement of blood lead concentrations and inhibition of erythrocyte θ-amino levulinic acid dehydratase activity (ALA-D) has been used successfully to diagnose lead exposure in human populations. While blood lead is one of the best indicators of lead exposure, its measurement is expensive, time consuming, subject to bias through contamination and requires highly skilled personnel. The advantages of assaying ALA-D activity are those of cost, speed, sample size and simplicity. Since most organisms possess this enzyme in a variety of tissues, and since its activity is inhibited only by lead, there is potentially a large variety of aquatic species that may be used to monitor “biologically available” lead in aquatic ecosystems. Sessile and migratory species could integrate short-term fluctuations in waterborne lead and provide data on spatial and temporal variations. Fish are convenient organisms to sample and fish blood is a particularly rich source of ALA-D. Laboratory experiments have defined the optimum conditions for blood sampling and assaying ALA-D activity as well as the strong negative correlation between blood lead concentrations and ALA-D activity and between waterborne lead concentrations and ALA-D activity. Other toxic metals (e.g. Cu, Hg, Zn, Cd) and PCB's do not inhibit ALA-D, and factors that increase lead toxicity (e.g. decreased environmental pH) also increase lead uptake and the inhibition of ALA-D. Consequently, ALA-D activity provides a measure of both exposure and effect. Species variation in rates of lead uptake allows a selection of a suitable monitoring species for a given, situation. Preliminary surveys of Lake Ontario fish populations indicate that monitoring of ALA-D activity is technically simple and straightforward, the assay is much cheaper and faster than blood lead or whole body lead analyses, and activity is correlated to other measures of lead in fish.


PEDIATRICS ◽  
1989 ◽  
Vol 84 (4) ◽  
pp. 604-612
Author(s):  
Rakesh Shukla ◽  
Robert L. Bornschein ◽  
Kim N. Dietrich ◽  
C. R. Buncher ◽  
Omer G. Berger ◽  
...  

The growth of a cohort of 260 infants was prospectively followed up from birth. Blood lead and stature measurements were obtained every 3 months until 15 months of age. Fetal lead exposure was indexed by measuring lead in maternal blood during pregnancy. A longitudinal analysis revealed that covariate adjusted growth rates in stature were negatively related to the infants' postnatal blood lead concentration, as indexed by increase in average blood lead values from 3 to 15 months. However, this relationship between growth rate and change in blood lead concentration was evidenced only among those infants whose mothers had prenatal blood lead levels greater than the maternal cohort median of 7.7 γg/dL (P = .01). The expected stature of a child born to a mother with a prenatal blood lead concentration more than 7.7 γg/dL is about 2 cm shorter at 15 months of age if, postnatally, the infant incurred a 10-γg/dL blood lead increase during the 3-to 15-month interval of life, compared with an infant who has no increase.


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