And Delta-aminolevulinic Acid Dehydratase Research Articles

Association between Blood Lead Levels and Heme Synthesis Process in Paint Industry Workers

Lead is a heavy metal that can pose various health risks to humans. One of the effects of lead exposure is the inhibition of the delta-ALAD enzyme which plays a role in the heme synthesis process. Blood lead levels and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity respectively. The inhibition of ALAD can cause in accumulation of ALA in urine and also inhibit the heme synthesis pathway that plays a role in hemoglobin production. The present study was designed to investigate the association between the BLLs and the heme synthesis process, which is detected by the accumulation of urinary ALA (ALA-U) and decreasing hemoglobin, in paint industry workers from Indonesia. A total of 52 paint industry workers participated in this study. Blood lead was measured using ICP-MS and ALA-U was measured using spectrophotometer method. Mean blood lead was 4.213±1.6 mg/L; and 17 workers (32.7%) crossed the recommended level of 5 mg/L. Mean urinary ALA level was 3.712±2.5 mg/L; and 11 workers (11.54%) crossed the normal level of 6 mg/L but still classified as acceptable. Mean hemoglobin level was 15.273±1.03 g/L. The correlation between the BLL and ALA-U was found to be positive but not significant. Meanwhile, the correlation between the ALA-U and the hemoglobin levels was found to be negative but also not significant.

Biomonitoring findings for occupational lead exposure in battery and ceramic tile workers using biochemical markers, alkaline comet assay, and micronucleus test coupled with fluorescence in situ hybridisation.

Manufacture of lead-containing products has long been associated with various health risks. To get an insight into the related genotoxic risks, we conducted a biomonitoring study in 50 exposed workers and 48 matched controls using a battery of endpoints that sensitively detect the extent of genome instability in peripheral blood lymphocytes. The levels of primary DNA damage were estimated with the alkaline comet assay, while cytogenetic abnormalities were determined with the cytokinesis-block micronucleus (CBMN) cytome assay. Additionally, CBMN slides of 20 exposed and 16 control participants were subjected to fluorescence in situ hybridisation (FISH), coupled with pancentromeric probes to establish the incidence of centromere-positive micronuclei, nuclear buds, and nucleoplasmic bridges. Blood lead levels (B-Pb) were measured with atomic absorption spectrometry. To further characterise cumulative effects of occupational exposure, we measured erythrocyte protoporphyrin (EP) concentrations and delta-aminolevulinic acid dehydratase (ALAD) activity in blood. We also assessed the influence of serum folate (S-folate) and vitamin B12 (S-B12) on genome stability. Compared to controls, occupationally exposed workers demonstrated significantly higher B-Pb (298.36±162.07 vs 41.58±23.02), MN frequency (18.71±11.06 vs 8.98±7.50), centromere positive MN (C+ MN) (8.15±1.8 vs 3.69±0.47), and centromere negative MN (C- MN) (14.55±1.80 vs 4.56±0.89). Exposed women had significantly higher comet tail intensity (TI) and length (TL) than control women. Furthermore, workers showed a positive correlation between age and nuclear buds and MN, between MN and years of exposure, and between S-B12 levels and TI and ALAD activity, while a negative correlation was found between TI and B-Pb. These findings suggest that occupational settings in the manufacture of lead-containing products pose significant genotoxic risks, which calls for developing more effective work safety programmes, including periodical monitoring of B-Pb and genetic endpoints.

Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase in Pregnant Women.

Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13–43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs < 5 µg/dL (p = 0.002). To reduce the influence of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A significant negative correlation between blood lead and ALAD activity was observed in the fourth quartile of BLLs (r = −0.113; p < 0.01). Among women with blood lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = −0.413; p < 0.01). Multiple linear regression demonstrated that inhibition of ALAD in pregnant women may occur at levels of lead in blood above 2.2 µg/dL.

Influence of abatement of lead exposure in Croatia on blood lead and ALAD activity

We evaluated the effect of lead (Pb) abatement measures in Croatia on blood lead (BPb) concentrations, and delta-aminolevulinic acid dehydratase (ALAD) activity in blood, as a sensitive indicator of early Pb effect. Data on BPb and ALAD activity were obtained from 829 Croatian men (19-64 years of age), with no known occupational exposure to metals. Data obtained in 2008-2009, after the ban of leaded gasoline in Croatia in 2006, were compared with similar data collected in 1981 and 1989, when the concentration of Pb in gasoline was 0.6 g/L. Our results showed a highly significant (p < 0.001) decrease in median BPb from 114.5 (range, 46.0-275.0) μg/L in 1981/1989 to 30.3 (range, 3.2-140.8) μg/L in 2008-2009 and an increase in median ALAD activity from 49.8 (range, 24.9-79.4) EU in 1981/1989 to 60.9 (range, 35.8-84.0) EU in 2008-2009. Individual factors influencing BPb values were, in the order of decreasing importance, Pb in ambient air (APb), alcohol consumption, age, and smoking. Increased ALAD activity was significantly associated with the decrease of APb, alcohol consumption, and smoking. These results show that lead abatement measures had a positive impact on both BPb concentrations (73.5% decrease) and the activity of ALAD (22.1% increase) in general population. Our results contribute to growing evidence that ALAD activity may be used as one of the earliest and sensitive diagnostic biomarkers of low-level Pb exposure.

Associations between patella lead and blood pressure in lead workers

To compare associations of patella lead, a lead pool that may capture aspects of both current bioavailable and cumulative lead dose thus offering advantages over tibia or blood lead, with blood lead in models of blood pressure and hypertension and to examine effect modification by age, sex and polymorphisms of the genes encoding for the vitamin D receptor (VDR) and delta-aminolevulinic acid dehydratase (ALAD). Cross-sectional data in 652 current and former lead workers were analyzed. Blood lead, but not patella lead, was positively associated with systolic blood pressure. Neither lead measure was associated with diastolic blood pressure or hypertension status. There was no evidence of effect modification. In these workers, blood lead was more relevant to elevations in blood pressure than was patella lead. Additional research will be required to determine whether patella lead assessment provides unique information on vascular risk from lead exposure.

Aminolevulinic acid dehydratase activity in American dippers (Cinclus mexicanus) from a metal‐impacted stream

Blood samples collected from adult and nestling American dippers (Cinclus mexicanus) along the Arkansas River (CO, USA), a stream impacted by discharges from historical mining operations, and a reference stream were analyzed for lead concentration and delta-aminolevulinic acid dehydratase (ALAD) activity. Median ALAD activities of adult and nestling dippers from the Arkansas River were found to be significantly different from median ALAD activities of reference adults and nestlings (p = 0.002 and p = 0.028). Median ALAD activity for adult dippers from the Arkansas River was more than 50% lower relative to reference adults and activity approached a level close to 50% lower in nestlings from the same site. Median blood lead concentrations from adult (range 15.4-386.0 ppb) and nestling (range 12.1-323.0 ppb) dippers from the Arkansas River were found to be significantly different from median blood lead concentrations of reference adult (range 4.2-29.6 ppb) and nestling (range 4.2-8.2 ppb) dippers (p < 0.001 and p = 0.011). The median hematocrit level in adult dippers did not vary between sites (p = 0.73), whereas the median hematocrit level of nestling dippers from the reference site was significantly lower compared to Arkansas River nestlings (p = 0.042). Blood lead concentration in both adult and nestling dippers was found to be significantly correlated with invertebrate lead concentration (r = 0.81, p < 0.001 and r = 0.62, p = 0.01, respectively). Highly significant negative correlations were observed between blood lead concentration and ALAD activity in both adult and nestling dippers (r = -0.86, p < 0.001 and r = -0.84, p < 0.001, respectively). This study suggests that dippers (both adults and nestlings) from the Arkansas River have significantly lower ALAD activity and significantly higher blood lead concentrations compared to reference values. The measurement of ALAD activity may be a sensitive and accurate biomarker for environmental lead exposure in dippers.

Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes.

Evidence suggests that lead and selected genes known to modify the toxicokinetics of lead--namely, those for the vitamin D receptor (VDR) and delta-aminolevulinic acid dehydratase (ALAD)--may independently influence blood pressure and hypertension risk. We report the relations among ALAD and VDR genotypes, three lead dose measures, and blood pressure and hypertension status in 798 Korean lead workers and 135 controls without occupational exposure to lead. Lead dose was assessed by blood lead, tibia lead measured by X-ray fluorescence, and dimercaptosuccinic acid (DMSA)-chelatable lead. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele, and there were no ALAD(2) homozygotes; 11.2% (n = 89) had at least one copy of the VDR B allele, and 0.5% (n = 4) had the BB genotype. In linear regression models to control for covariates, VDR genotype (BB and Bb vs. bb), blood lead, tibia lead, and DMSA-chelatable lead were all positive predictors of systolic blood pressure. On average, lead workers with the VDR B allele, mainly heterozygotes, had systolic blood pressures that were 2.7-3.7 mm Hg higher than did workers with the bb genotype. VDR genotype was also associated with diastolic blood pressure; on average, lead workers with the VDR B allele had diastolic blood pressures that were 1.9-2.5 mm Hg higher than did lead workers with the VDR bb genotype (p = 0.04). VDR genotype modified the relation of age with systolic blood pressure; compared to lead workers with the VDR bb genotype, workers with the VDR B allele had larger elevations in blood pressure with increasing age. Lead workers with the VDR B allele also had a higher prevalence of hypertension compared to lead workers with the bb genotype [adjusted odds ratio (95% confidence interval) = 2.1 (1.0, 4.4), p = 0.05]. None of the lead biomarkers was associated with diastolic blood pressure, and tibia lead was the only lead dose measure that was a significant predictor of hypertension status. In contrast to VDR, ALAD genotype was not associated with the blood pressure measures and did not modify associations of the lead dose measures with any of the blood pressure measures. To our knowledge, these are the first data to suggest that the common genetic polymorphism in the VDR is associated with blood pressure and hypertension risk. We speculate that the BsmI polymorphism may be in linkage disequilibrium with another functional variant at the VDR locus or with a nearby gene.

Biomarkers and fluctuating asymmetry as indicators of pollution‐induced stress in two hole‐nesting passerines

Abstract1. The stress caused by air pollutants was studied at biochemical, morphological and ecological levels in the Pied Flycatcher, Ficedula hypoleuca, and Great Tit, Parus major, nestlings in 10 study sites along the pollution gradient of a copper smelter.2. First, stress was measured using four biomarkers from blood and liver: ethoxyresorufin O‐deethylase (EROD) enzyme, haemoglobin, stress protein Hsp70 and delta‐aminolevulinic acid dehydratase (ALA‐d) enzyme. Second, the amount of fluctuating asymmetry (FA) in the length of the 3rd primary and the outermost rectrix (in P. major) and the length and thickness of the tarsus were measured. These stress indicators were further examined in relation to the breeding performance of birds, i.e. the ecological response.3. EROD activity was increased in F. hypoleuca nestlings near the pollution source. In P. major, it was not related to the pollution gradient but correlated well with the proportion of starved nestlings, i.e. the nutritional stress during the nestling period. The variations in haemoglobin, Hsp70 and ALA‐d enzyme activity were not significantly related to pollution gradient.4. The tarsus length of F. hypoleuca nestlings and primary length of P. major nestlings showed increased asymmetry in the vicinity of the pollution source. Breeding success decreased towards the pollution source in both species.5. In F. hypoleuca, the pollution‐related stress was verified at all three target levels. In P. major, pollution‐related effects were found at morphological and ecological levels but not at the biochemical level, which suggests that direct toxic effect of heavy metals was not the main mechanism in this species.

Effect of lead exposure on some biological indices related to porphyrin metabolism and the activity of erythrocyte pyrimidine 5?-nucleotidase in the mice

The urinary excretion of delta-aminolevulinic acid (ALA) and coproporphyrin (CP) isomers (I and III) was investigated in mice exposed to lead in drinking water (200 and 500 ppm) for 14 or 30 days. Furthermore, the inhibition of pyrimidine 5'-nucleotidase (P5N) and delta-aminolevulinic acid dehydratase (ALAD) was studied in the same mice. In the lead-exposed mice, urinary excretion of ALA was significantly elevated (12-times control), while that of CP remained unchanged. This discrepancy on the urinary excretion may be of interest. The P5N activity in both erythrocytes and bone marrow cells was significantly inhibited by exposure to lead. However, the degree of inhibition was greater in the erythrocytes (45% inhibition) than in the bone marrow cells (25% inhibition). The inhibition of ALAD was much higher in erythrocytes (90% inhibition) than in liver (20-40% inhibition). The increase in erythrocyte protoporphyrin and the decrease in both hemoglobin and hematocrit were not observed in mice exposed to lead under the above conditions.

The effect of lead and cadmium on liver, kidney, and brain levels of cadmium, copper, lead, manganese, and zinc, and on erythrocyte ALA-D activity in mice

Lead and cadmium were administered intraperitoneally, singly and jointly, to the mice. The levels of cadmium, copper, manganese, lead and zinc were determined in liver, kidney and brain by atomic absorption spectrophotometric technique and delta-aminolevulinic acid dehydratase (ALA-D) activity was determined in erythrocytes. The tissue levels of some of these metals were found significantly altered by cadmium and lead both, but cadmium was found to have no effect on blood on ALA-D activity.

LENNOX'S SYNDROME AND LEAD INTOXICATION

Three male and two female children with Lennox's syndrome linked etiologically with lead intoxication were followed for up to three years. The diagnosis of Lennox's syndrome was made on the basis of clinical and EEG findings which are categorized in detail. Biochemical determinations used for the detection of "undue absorption of lead" were lead blood levels, urinary lead excretion, and delta-amino-levulinic-acid dehydratase (ALA-D) concentration in erythrocytes, considering a positive diagnosis of lead intoxication upon the finding of decreased enzymatic activity plus values higher than normal for lead blood levels or lead excretion in urine. Significant improvement in the EEG abnormalities and/or the number of seizures has been observed in these five patients after specific treatment of their plumbism, without changes being made in the concomitant anticonvulsant therapy. Two patients are free of seizures and their EEGs became normal. Two other patients had only one seizure in the last year and their EEGs now show only sporadic spike foci. These findings open new possibilities for etiological diagnosis and therapeutic approach for some of the patients with chronic epileptic encephalopathies with slow spike-and-wave discharges in the EEG.