δ-Aminolevulinic acid dehydrase as a measure of lead exposure.
TL;DR: Ierythrocyte ALA-D is more accurate and more sensitive than ALA in urine as an indicator of the amount of circulating lead and can be used as a screening procedure to exclude a lead absorption over a given level.
Abstract: Close negative correlation between the concentration of lead in blood (Pb-B) and the logarithm of erythrocyte δ-aminolevulinic acid dehydrase (ALA-D) was found for 159 persons with Pb-B levels ranging from 5μg to 95μg per 100 ml. A statistically significant correlation (r = 0.59) between Pb-B and δ-aminolevulinic acid (ALA) in urine was obtained only for Pb-B values over 50μg/100 ml. These results indicate that erythrocyte ALA-D is more accurate and more sensitive than ALA in urine as an indicator of the amount of circulating lead. It is suggested that ALA-D assays can be used as a screening procedure to exclude a lead absorption over a given level. Fairly accurate estimates of the mean Pb-B of groups of people can also be made from their mean ALA-D activity.
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01 Aug 2007
1,097 citations
Cites background from "δ-Aminolevulinic acid dehydrase as ..."
...ALAD, an enzyme occurring early in the heme pathway, is also considered a sensitive indicator of Pb effect (Graziano 1994; Hernberg et al. 1970; Morris et al. 1988; Somashekaraiah et al. 1990; Tola et al. 1973)....
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...ALAD activity is negatively correlated with PbBs of 5–95 μg/dL, with >50% inhibition occurring at PbBs >20 μg/dL (Hernberg et al. 1970; Morita et al. 1997; Roels and Lauwerys 1987)....
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Journal Article•
TL;DR: Lead poisoning in adults occurs more frequently during exposure in the workplace and primarily involves the central nervous system, with the most deleterious effects on the hemopoietic, nervous, reproductive systems and the urinary tract.
Abstract: Lead is a metal which has been associated with human activities for the last 6000 years. In ancient civilizations, uses of lead included the manufacture of kitchen utensils, trays, and other decorative articles. However, lead is also toxic to humans, with the most deleterious effects on the hemopoietic, nervous, reproductive systems and the urinary tract. The main sources of lead exposure are paints, water, food, dust, soil, kitchen utensils, and leaded gasoline. The majority of cases of lead poisoning are due to oral ingestion and absorption through the gut. Lead poisoning in adults occurs more frequently during exposure in the workplace and primarily involves the central nervous system. Symptoms of hemopoietic system involvement include microcytic, hypochromic anemia with basophilic stippling of the erythrocytes. Hyperactivity, anorexia, decreased play activity, low intelligence quotient, and poor school performance have been observed in children with high lead levels. Lead crosses the placenta during pregnancy and has been associated with intrauterine death, prematurity, and low birth weight. In 1991, the Centers for Disease Control and Prevention in the USA redefined elevated blood lead levels as those > or = 10 microg/dl and recommended a new set of guidelines for the treatment of lead levels > or =15 microg/dl.
445 citations
Cites background from "δ-Aminolevulinic acid dehydrase as ..."
...Because this enzyme is normally present in great quantities, the inhibition of its activity may pass unnoticed [30,31]....
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TL;DR: Today's research focuses on the effects of low exposure, often with the aim of defining noneffect levels for different types of effects.
Abstract: Lead poisoning existed and was already known in Antiquity but was forgotten, at least in the literature, until the end of the Middle Ages, where it was mentioned sporadically. In the 19th century this disease, which reached epidemic dimensions during the period of industrialization, was "rediscovered." Several comprehensive clinical articles appeared in the literature. The clinical picture deepened during the beginning of the 20th century, and preventive efforts were started. However, the concept of poisoning remained strictly clinical. During the latter half of the 20th century a new concept emerged: subclinical and early forms became recognized as undesirable effects. This led to a substantial lowering of hygienic standards. Pediatric poisoning has also been a serious problem during the 20th century. After the 1920s, environmental pollution by lead caused by the introduction of tetraethyl lead in gasoline became an alarming public health problem. The use became restricted in the 1980s; its effects on blood lead levels are now evident. Today's research focuses on the effects of low exposure, often with the aim of defining noneffect levels for different types of effects.
345 citations
Cites result from "δ-Aminolevulinic acid dehydrase as ..."
...These ®ndings, in combination with another study also including lead workers, suggested the absence of a threshold level [Hernberg et al., 1970]....
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23 Feb 2011
252 citations
Cites background from "δ-Aminolevulinic acid dehydrase as ..."
...However, the first measurable biochemical change resulting from lead absorption appears to be the inhibition of erythrocyte ALAD activity (Hernberg et al. 1970, Tola et al. 1973)....
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TL;DR: Of the biomarkers of lead exposure, blood lead (Pb-B), mainly red cell lead, is a representative of soft tissue lead, and most widely used as measures of body burden and absorbed (internal) doses of lead.
Abstract: Biomarkers of exposure, effect, and susceptibility are reviewed in relation to lead exposure. Of the biomarkers of lead exposure, blood lead (Pb-B), mainly red cell lead, is a representative of soft tissue lead, and most widely used as measures of body burden and absorbed (internal) doses of lead. Urine lead (Pb-U) as well as plasma lead (Pb-P) increases exponentially with increasing Pb-B under a steady-state situation and is a reflection of recent exposure. The amount of lead in plasma and urine (MPb-P and MPb-U) after administration of a chelating agent (e.g. CaEDTA) can be useful for biomarkers of internal exposure of lead, reflecting the mobilizable pool of lead which consists of mainly blood and soft tissue lead with only a small fraction derived from bones. The critical effects in bone marrow arise mainly from the interaction of lead with some enzymatic process responsible for heme synthesis. The effects can be used for the biomarkers of effects. They are the inhibition of delta-aminolevulinic acid dehydratase (ALAD) and the variation in some metabolite concentrations (e.g. delta-aminolevulinic acid in urine (ALA-U), blood (ALA-B) or plasma (ALA-P), coproporphyrin in urine (CP), zinc protoporphyrin (ZP) in blood). The activities of pyrimidine nucleotidase (P5'N) and nicotinamide adenine dinucleotide synthetase (NADS) in blood are also decreased in lead exposure, and nucleotide contents in blood is altered in lead exposure. These effects of lead on human can be also useful biomarkers of effect. The differences in levels of heme precursors between two types of ALAD genotypes might be attributable to those in the affinity of different ALAD isozymes to lead. ALAD1 homozygotes have higher levels of ZP and ALA in comparison with ALAD2 carriers at the high lead exposure, suggesting that ALAD1 homozygotes might be more susceptible for disturbance in heme biosynthesis by lead than ALAD2 carriers.
197 citations
References
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TL;DR: The results indicate that present levels of environmental contamination with lead can produce a measurable biochemical alteration in man.
164 citations
TL;DR: This review is an attempt to draw together at least some of the theories which have been advanced in the past and to present them, it is hoped, in an easily accessible manner for future workers in this field.
Abstract: Lead intoxication has been recognized as a clinical entity since ancient times Hippocrates (370 BC) was probably the first person to associate lead with clinical symptoms, since when the harmful effects of lead on the body have been well documented Early observations culminated in the brilliant monograph of Tanquerel des Planches (1839) in which the clinical aspects of the disease were completely outlined and most of the early signs of the disease were mentioned So complete was this work that virtually nothing has been added to des Planches9s observations since their publication The earliest reference to lead anaemia was made in 1831 by Laennec, who described thinness of the blood and pallor of the tissues in cases of lead poisoning at necropsy The first direct evidence of the effect of lead on red blood cells was presented by Andral and Gavarret (1840), who counted the number of red blood cells in cases of lead poisoning and found the count to be much lower than normal Since these early reports a great deal of work has been undertaken to try to discover the means by which lead causes anaemia, but it is probably true to say that at the present time this mechanism is still not fully understood This review is an attempt to draw together at least some of the theories which have been advanced in the past and to present them, it is hoped, in an easily accessible manner for future workers in this field
140 citations
TL;DR: It is concluded that the determination of ALA dehydratase activity in erythrocytes offers an excellent measure for the evaluation of lead poisoning and that administration of reduced glutathione seems to be useful for treating patients with lead-poisoning.
111 citations
TL;DR: The aim of the study was to establish the relationships between the three parameters during constant exposure, and those who showed comparatively high ALA and urinary lead values in relation to their blood lead level were found to be workers with repeated incidents of metabolic lead influence.
Abstract: Selander, S., and Cramer, K. (1970).Brit. J. industr. Med.,27, 28-39. Interrelationships between lead in blood, lead in urine and ALA in urine during lead work. One hundred and seventy-seven workers from a storage battery factory were examined for lead in blood and lead and δ-aminolevulinic acid (ALA) in urine. The workers were selected at random from those who had been employed for more than one month;most had been employed for several years at the same job. Thirty-six workers were from departments with no lead exposure. In three departments with high exposure a rotating system with three weeks9 exposure and three weeks9 non-exposed work was applied. As the aim of the study was to establish the relationships between the three parameters during constant exposure, the values from these men were treated separately. The relationship between lead in blood and urinary ALA was best described by a curvilineat function: ALA = 100·0157 Pbb-1·0985, while the regression lines for ALA on lead in urine, and lead in urine on lead in blood were straight. Workers from the departments with the rotating system showed lower values for urinary lead and ALA, compared with non-rotating workers with the same level of lead in blood. All these workers were examined during their second or third week of lead work, i.e., with an accumulating lead body burden. This system may be beneficial, especially in departments where prophylactic measures are difficult to install, or for notoriously careless workers. Those who showed comparatively high ALA and urinary lead values in relation to their blood lead level were found to be workers with repeated incidents of metabolic lead influence, in whom the ALA values had seldom been normal. The mean values from different factory departments were of the same order as would be expected from previous studies in storage battery plants. The results are discussed in relation to present concepts of lead absorption and poisoning.
96 citations