Relationship between activation of delta-aminolevulinic acid dehydratase by heating and blood lead level

Both blood lead and erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) activity were determined for workers with and without an occupational lead exposure.In workers occupationally exposed to lead, it was demonstrated that the erythrocyte ALA-D is markedly activated by heating the hemolysate at 60° C for 5 min and there is a good positive correlation between the ratio of heated to nonheated ALA-D activity and the blood lead level (r = 0.799). In addition, by heating the hemolysate, the ALA-D activity of the lead-exposed workers appears to be returned into the normal range regardless of the extent of lead absorption. However, in normal workers without the occupational lead exposure, no significant correlation was found between the ratio of heated to nonheated ALA-D activity and the blood lead level, although the normal ALA-D also can be slightly activated by heating the hemolysate at 60° C for 5 min.     

Comparative study of effects of lead on the activity of erythrocyte pyrimidine 5′-nucleotidase and delta-aminolevulinate dehydratase in vivo and in vitro

The effect of lead on the activities of erythrocyte pyrimidine 5′-nucleotidase (Py5N) and delta-aminolevulinate dehydratase (ALA-D) was studied in the mice which were given ad libitum a drinking water containing lead of 10, 50 and 250 ppm, for 27 days. The erythrocyte Py5N activity was not decreased in all groups of lead-exposed mice. However, the erythrocyte ALA-D activity was markedly decreased in the groups exposed to 50 and 250 ppm lead. These data indicate that erythrocyte ALA-D is more sensitive than Py5N to lead in vivo. On the other hand, from the in vitro study, it was demonstrated that the human erythrocyte Py5N is moderately inhibited by zinc and tin, and markedly by mercury, cadmium, silver, copper, and lead, at 10⁻⁴ molar concentrations. In addition, it was observed that the erythrocyte Py5N is most remarkably inhibited by mercury while the ALA-D by lead, among metals tested.     

Effect of lead on the activity of erythrocyte porphobilinogen deaminase in vivo and in vitro

The effect of lead on the activity of erythrocyte porphobilinogen deaminase (PBGD) in vivo and in vitro was investigated using blood specimens obtained from controls and lead-exposed workers. When lead nitrate was added to the incubation mixture at a final concentration of 10⁻⁴ M, 83% inhibition of erythrocyte PBGD activity was found. However, in workers occupationally exposed to lead, no inhibition of erythrocyte PBGD activity was detected. This finding indicates that the erythrocyte PBGD test is not useful for evaluating exposure to lead in workers. In addition, the in vitro study confirmed that mercuric chloride strongly inhibits erythrocyte PBGD activity.     

Effect of lead on electrophoretic mobility of rat erythrocytes

Lead often affects the erythrocyte membrane. The relationship between the changes in erythrocyte membrane and the anemia caused by lead is still unclear. Initially, the effect of lead injected intraperitoneally on the electrophoretic mobility of rat erythrocytes was investigated in order to study the relationship between them. As indices of lead exposure, hemoglobin (Hb) levels, hematocrits (Ht), δ-aminolevulinic acid dehydratase (ALA-D) activities and blood lead (blood Pb) levels in the injected rats were also examined. Exposure to lead significantly decreased the mobility of rat erythrocytes. The changes in mobility seemed to be less sensitive than those in ALA-D activity, however, the decreases in mobility were simultaneous with or prior to those in Hb level and Ht. The decreases in mobility were evident to some extent below a blood Pb level of 100 μg/100 ml and generally present at a level of 100 μg/100 ml and over. In the rats exposed to lead a significant negative correlation was found between the mobilities and the logarithms of blood Pb level.     

Species difference of urinary excretion of delta-aminolevulinic acid and coproporphyrin in mice and rats exposed to lead

The urinary excretion of delta-aminolevulinic acid (ALA) was first investigated in mice exposed to lead in the drinking water (500 ppm) for 30 days, and the results were compared with those obtained from rats exposed to lead under the same exposure condition. The result indicated that the level of urinary ALA excretion in lead-exposed mice was much higher than that in lead-exposed rats. This finding suggests a species difference between mice and rats with regard to sensitivity to lead. On the other hand, urinary coproporphyrin (CP) was also determined in rats and mice exposed to lead. The result obtained indicated that the increasing level of urinary CP excretion was higher in rats than in mice, contrary to expectation. The reason for the discrepancy between urinary excretion of ALA and that of CP in rats and mice exposed to lead is, however, unknown.     

Relationship between lead concentration in blood and the activities of erythrocyte pyrimidine 5′-nucleotidase and delta-aminolevulinate dehydratase in the mice exposed to lead

The relationship between the activities of both pyrimidine 5-nucleotidase (Py5N) and delta-aminolevulinate dehydratase (ALA-D) in erythrocytes and the concentration of lead in blood was investigated in the mice which were given ad libitum a drinking water containing lead of 10 to 500 ppm, for 30 days.From these results, it was demonstrated that the erythrocyte PySN activity is inhibited by lead and its activity level is negatively correlated with the concentration of lead in blood (r=–0.78). In addition, it was suggested that the erythrocyte Py5N activity is a better indicator in the exposure to relatively high lead concentration while the ALA-D is a more sensitive indicator for evaluating the lead exposure of low and moderate levels.     

Delta-aminolaevulinic acid metabolism in normal and lead-exposed humans

The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid synthetase (ALA.S) and delta-aminolaevulinic acid dehydratase (ALA.D) were measured in the peripheral blood of a group of lead workers and control subjects. The haem precursor delta-aminolaevulinic acid (ALA) was measured in blood and urine, whilst lead levels were measured in whole blood. The inter-relationships between all these parameters were examined and quantified. The results demonstrate that above a blood lead concentration of 2 mumole/l and below an erythrocyte ALA.D activity of 18 nmole ALA utlized/min/ml red blood cells (R.B.C.), Haem synthesis is depressed to such an extent that the activity of leucocyte ALA.S, the rate-limiting enzyme of haem biosynthesis, is increased by negative feedback.     

Effects of Exposure to Lead on Selected Biochemical and Haematological Variables

Abstract: Blood and urine samples were taken from 34 persons occupationally exposed to lead and from 56 non-exposed control persons and blood lead and haemoglobin concentrations, red blood cell count, erythrocyte glutathione peroxidase (GSH-peroxidase) and acetylcholinesterase (AChE), and urinary δ-aminolevulinic acid were determined. Blood lead concentrations of the lead-exposed subjects were within the range generally accepted as safe for occupationally-exposed adults in many countries (i.e. below 50 μg Pb/dl blood). Yet, significant dose-dependent elevations were found in erythrocyte GSH-peroxidase and urinary δ-aminolevulinic acid. The urinary δ-aminolevulinic acid concentration of lead-exposed smokers was significantly elevated over that of lead-exposed non-smokers. Smoking did not affect the urinary δ-aminolevulinic acid concentration of control persons. In addition, a statistically significantly lower red blood cell count was observed in the lead-exposed group. Our results indicate that the above described safety standard for blood lead concentrations in occupationally exposed adults, although generally accepted, needs revision.     

Benchmark dose approach for renal dysfunction in workers exposed to lead

Benchmark dose (BMD) and the lower confidence limit on the benchmark dose (BMDL) of blood lead were estimated to explore the biologic exposure limits for renal dysfunction caused by lead. One hundred thirty-five workers from one storage battery plant were selected as lead exposure group while 143 mechanics as the control. The relationship between the blood lead concentration and the urinary excretion of total protein (TP), beta2-microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG) was studied. The quantal linear logistic regression model (BMDS Version 1.3.1) was used to calculate BMD and BMDL of blood lead. The results showed that the levels of NAG, beta2-MG, and TP in lead-exposed workers were higher than those of control group and elevated along with rising length of employment. The levels of three indices for renal dysfunction increased with the elevated blood lead. The BMD and BMDL of blood lead for renal dysfunction were from 299.4 to 588.7 microg/L and from 253.4 to 402.3 microg/L, respectively. The BMDL of blood lead was ranged from high to low as TP, beta2-MG, and NAG. It is suggested that the urinary NAG activity could be a sensitive and early biomarker of renal tubular dysfunction induced by lead. When assessing renal function in workers occupationally exposed to lead, a blood lead level of 250 microg/L could serve as a warning signal.     

Effects of lead on thyroid functions in lead-exposed workers

Lead exposure is a common public health problem. Exposure to the metal can cause hematological, gastrointestinal, rheumatological, endocrine, neurological and renal problems in humans. However, effects on the thyroid gland are controversial. We retrospectively investigated thyroid function parameters in 65 adult males who had been occupationally exposed to lead. We then compared the findings with those of 60 male patients who had no history of lead exposure or thyroid abnormalities, who served as the control group. The mean ages of the lead-exposed workers and the controls were 34.3 ± 7.9 and 32.9 ± 6.6 years respectively. Blood lead levels in the lead-exposed workers were significantly higher than in the control group. The lead-exposed workers were assigned to one of three groups according to their blood lead levels, as follows: 40–59 μg/dl, 60–79 μg/dl, or 80 μg/dl and above. Thyroid Stimulating Hormone (TSH) levels in the 80 μg/dl and above group were significantly higher than in either the 40–59 μg/dl group or the 60–79 μg/dl group. However, TSH levels in the 40–59 μg/dl group did not differ significantly from those in the 60–79 μg/dl group. These results suggest that high levels of lead in the blood may affect thyroid physiology. Clinicians should be aware of the potential hazardous effects of lead on the thyroid, especially in patients who have been occupationally exposed to lead.     

Correlation between clinical indicators of lead poisoning and oxidative stress parameters in controls and lead-exposed workers

The present study was undertaken to investigate the involvement of oxidative damage in lead-induced toxicity in humans and to enlighten whether oxidative stress indicators are correlated with the known indices of lead toxicity. For these purposes, selected oxidative stress parameters along with some clinical indices of lead poisoning were determined in blood of battery plant workers and control subjects. Workers had significantly increased erythrocyte malondialdehyde (MDA) levels, catalase and glucose-6-phosphate dehydrogenase (G6PD) activities, and decreased blood glutathione:glutathione disulfide ratio compared to the controls. Increased blood lead concentrations and zinc protoporphyrin (ZPP) levels, and decreased delta-aminolevulinic acid dehydratase (ALAD) activity were used as clinical indices of lead toxicity. Statistically significant correlation between oxidative stress parameters and clinical indices implies that disrupted prooxidant/antioxidant balance might contribute to lead-induced toxicity in erythrocytes. A significant correlation was found between ALAD activity and blood lead levels in human subjects. Similarly significant correlation between ALAD activity and erythrocyte MDA concentrations was shown. Present data indicates that ALAD can serve as a valuable biomarker of oxidative stress in lead-exposed hematological system as well as being a biochemical indicator of lead exposure.     

Elevated urinary excretion of beta-aminoisobutyric acid and delta-aminolevulinic acid (ALA) and the inhibition of ALA-synthase and ALA-dehydratase activities in both liver and kidney in mice exposed to lead.

Urinary excretion of beta-aminoisobutyric acid (ABA) and delta-aminolevulinic acid (ALA) was investigated in mice exposed to lead (500 p.p.m.) in drinking water for 14 days. Concentrations of both urinary ABA and urinary ALA increased significantly in the lead-exposed mice. However, the degree of increasing excretion was higher in urinary ALA (10-fold of the control) than in urinary ABA (2-fold of the control). On the other hand, it was demonstrated that ALA dehydratase in liver and kidney is inhibited by exposure to lead, while ALA synthase in these tissues has no inhibitory effect.     

Serum succinyltrialanine p-nitroanilide-hydrolytic activity in workers occupationally exposed to lead

The relationship between blood lead concentration and serum succinyltrialanine p-nitroanilide-hydrolytic (STN) activity was investigated in 74 workers occupationally exposed to lead and in 28 non-exposed workers. Exposure to lead was observed during transfer-printing processes in which paints or paint powders containing 20-50% lead were used. The mean lead concentration was 0.49 mg/m3 (0.12-1.43 mg/m3) in the working environment and 1.42 mg/m3 (0.21-4.34 mg/m3) in workers involved in printing processes. Serum STN activity became lower with increasing concentrations of blood lead (PbB) in non-exposed workers (controls). In lead-exposed workers, the activity decreased with increasing concentrations of PbB of 2.0 mumol/l and more, but increased when less than 1.9 mumol/l. Among lead-exposed workers with high PbB concentrations and/or with hepatic dysfunction, the STN/PbB ratio was distributed above the regression line obtained from the controls. The present investigation suggests that serum STN activity decreases in those highly exposed to lead. Enzymes such as elastase, which hydrolyzes succinyltrialanine p-nitroanilide and additionally is not inhibited by lead, may possibly be induced among lead workers when liver function is impaired.     

Effects of lead on sialic acid content and survival of rat erythrocytes

The anemia frequently observed in lead poisoning is thought to result from a shortening of erythrocyte survival in combination with inhibition of hemoglobin synthesis. However, the exact mechanism by which lead shortens erythrocyte survival remains unclear. In the present study, the effects of lead, injected intraperitoneally, on sialic acid content and survival of rat erythrocytes were investigated in order to study the relationship between them. As indices of lead exposure, hemoglobin (Hb) levels, hematocrits (Ht) and blood lead (blood Pb) levels in the injected rats were also examined. Exposure to lead significantly decreased the sialic acid content of the erythrocyte membrane. The decreases in sialic acid content were evident to some extent below a blood Pb level of 100 micrograms/100 ml and generally present at a level of 100 micrograms/100 ml and higher. In the rats exposed to lead a significant negative correlation was found between sialic acid content and the logarithm of blood Pb level. A shortening of erythrocyte survival was also observed in the rats exposed to lead.     

Renal effects and erythrocyte oxidative stress in long-term low-level lead-exposed adolescent workers in auto repair workshops

Lead poisoning is an old but persistent public health problem in developing countries. The present study investigated blood lead levels and its effects on markers of renal function and parameters of erythrocyte oxidative stress in adolescent male auto repair workers in Turkey. Blood Pb level and the ALAD index (logarithm of activated -aminolaevulinic acid dehydratase/nonactivated -aminolaevulinic acid dehydratase) were measured as indicators of exposure to Pb. Markers of tubular damage urine N-acetyl--d-glucosaminidase (NAG), ₂-microglobulin (-2 MG), creatinine (Cr), uric acid (UA), and calcium, markers of glomerular filtration blood urea nitrogen (BUN), serum Cr, UA, and parameters of oxidative damage in erythrocyte were studied in 79 Pb-exposed adolescent and 71 healthy control subjects. Blood lead levels and ALAD index were found significantly higher in the study group than that of normal control group. BUN, UA level, and glomerular filtration rates were detected in normal range in the lead-exposed group. Urinary NAG excretion and calciuria were higher in the study group than in controls. Urinary excretion of NAG was positively correlated with the blood lead levels (r=0.427). There was no relationship between blood lead levels and UA or -2 MG in urine. Malondialdehyde and glutathione peroxidase levels were significantly elevated in lead-exposed adolescents than controls, but changes in the catalase and superoxide dismutase activities in lead-exposed adolescents did not reach statistical significance. In conclusion, chronic low-dose lead exposure seems as a cause of subtle renal impacts in adolescent workers of auto repair workshops. Lead-induced oxidative stress in erythrocytes probably contributes to these subclinical renal effects.     

Comparison of inhibition of erythrocyte pyrimidine 5'-nucleotidase and delta-aminolevulinic acid dehydratase by lead

The effect of lead on the activities of erythrocyte pyrimidine 5'-nucleotidase (P5N) and delta-aminolevulinic acid dehydratase (ALAD) was investigated in control and lead-exposed workers. The inhibitory effect of lead in vivo and in vitro was more remarkable on the ALAD than on the P5N activity values. It was demonstrated that the pH optimum of both ALAD and P5N in lead workers shifts to the acidic side (nearly pH 6.0) compared to that in control workers.     

The effects of α-tocopherol administration in chronically lead exposed workers

The aim of the study was to investigate whether α-tocopherol supplementation for workers who are chronically exposed to lead would normalize/improve the values of parameters that are associated with the lead-induced oxidative stress.Study population included chronically lead exposed males who were divided into two groups. Workers in the first group (reference group) were not given any antioxidants, while workers in the second group (αT group) received supplementation with α-tocopherol.After treatment, the blood lead and leukocyte malondialdehyde levels decreased significantly in the αT group compared to the baseline levels and reference group. However, the erythrocyte malondialdehyde, conjugated dienes, and lipofuscin levels significantly increased compared to the baseline levels. The glutathione level significantly increased compared with the baseline.Effects of supplementation with α-tocopherol on oxidative damage were not satisfactory. Therefore, there is no reason to administer α-tocopherol to workers chronically exposed to lead as a prophylaxis of lead poisoning.     

Urinary excretion of 5-hydroxyindoleacetic acid, delta-aminolevulinic acid and coproporphyrin isomers in rats and men exposed to lead

The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), delta-aminolevulinic acid (ALA) and coproporphyrin (CP) isomers (I and III) was investigated in rats and workers exposed to lead. Urinary excretion of 5-HIAA, which is the major metabolite of serotonin, was not influenced by the lead exposure. However, a significant increase in urinary ALA and CP was found in rats and workers exposed to lead. In particular, the urinary excretion of CP-III was markedly increased compared to that of CP-I in rats and workers exposed to lead.     

Chemical and biological monitoring of chronic lead poisoning in the rat. Implications to the assessment of hazard of low-level lead

A study on rats of the effects of lead on delta-aminolevulinate dehydratase (ALA-D) activity, and its pH-dependent maximal enzyme activity is reported. Over a 5-week period, the lead burden and ALA-D activity in kidney, liver and brain are documented. Lead concentrations in the organs, expressed as micrograms/g protein are in the sequence kidney greater than liver greater than brain and reach essentially a constant level after 3 days of exposure. This is consistent with the existence of an efficient mechanism removing lead from these organs. Lead affects the ALA-D in all three organs by reducing the activity and shifting the pH of maximum enzyme activity to more acidic values. In common with the lead levels, the ALA-D activity does not deteriorate beyond the levels reached after 3 days of exposure. The existence of a mechanism removing lead from the organs is further supported in a recovery study on blood and kidney, in which both lead level and ALA-D activity return essentially to normal values after 7 days of no exposure to lead.     

Interrelationships of glutathione reductase, 5-aminolevulinic acid dehydratase, and free sulfhydryl groups in the erythrocytes of normal and lead-exposed persons

Blood lead, erythrocyte glutathione reductase (GSSG-R), 5-aminolevulinic acid dehydratase (ALA-D), and free sulfhydryl (SH) groups were measured in normal subjects and in those with occupational exposure to lead. With increasing blood lead concentration the activity of GSSG-R rises and that of ALA-D decreases. There is also a fall in the level of free SH with rising blood lead concentrations. There is a high degree of correlation between these parameters, and it is suggested that the changes represent part of a biological control mechanism to compensate for the reduction of available sulfhydryl groups by lead ions.