Erythrocyte δ-aminolaevulinic Acid Dehydratase Activity and Blood Protoporphyrin Concentrations as Indices of Lead Exposure and Altered Haem Biosynthesis

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.

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.


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.


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 ◽  
...  

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.


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

2014 ◽  
Vol 122 (10) ◽  
pp. 1134-1140 ◽  
Author(s):  
Linda G. Kahn ◽  
Xinhua Liu ◽  
Biljana Rajovic ◽  
Dusan Popovac ◽  
Sharon Oberfield ◽  
...  

1982 ◽  
Vol 27 (2) ◽  
pp. 113-121 ◽  
Author(s):  
M. R. Moore ◽  
A. Goldberg ◽  
S. J. Pocock ◽  
A. Meredith ◽  
I. M. Stewart ◽  
...  

In two studies in the city of Glasgow, 236 mothers and their newly born infants and 117 mothers and their 6-weeks old children's environmental lead exposure were examined. In both studies blood lead concentrations were found to correlate significantly with the cube root of the domestic water lead concentrations. In the first study, multiple regression analyses of maternal blood lead and cord blood lead concentrations on other variables showed a significant negative correlation with gestational age. It was also noted that there was an annual fluctuation in maternal blood lead concentration with highest values in the autumn. In the second study, similar relationships were found. Although there was no association between blood lead and sex, age, place of birth or feeding method, as in the previous study, a significant association between social class and blood lead was found. This could be explained on the basis of the significant correlation between water lead and social class. In those mothers who breast fed, breast milk lead concentrations were found to correlate significantly with blood lead concentrations where breast milk lead was around one tenth of blood lead concentration. These studies emphasise the importance of water lead in the economy of environmental lead exposure to mothers and their unborn and newly born infants.


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.


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