Delta-aminolevulinic Acid Concentrations Research Articles

Dose-dependent effect of chronic exposure to lead acetate on the dynamics of the content of delta-aminolevulinic acid and essential trace elements in the serum of laying hens


 One of the most global and dangerous pollutants is considered to be lead, due to its ability to accumulate in living organisms, to be included in the metabolic cycle, to form highly toxic organometallic compounds, not being biodegradable. To study the chronic effects of lead acetate, an experiment was performed on laying hens of Lohmann Brown cross. For research, one control and three experimental groups were formed, 20 chickens in each. Birds of the experimental groups were administered lead acetate daily with compound feed in doses (in terms of metal): Group I – 50 mg/kg of feed, II – 75 mg/kg of feed, III – 150 mg/kg of feed. Access to water was not restricted. The birds of the control group received a complete diet without lead acetate. On the 30th, 90th, 120th days of the experiment and the 20th day after withdrawal of the toxicant (the 140th day of the experiment), we took blood samples from birds for biochemical and toxicological studies. The concentration of delta-aminolevulinic acid (δ-ALA) in the serum of laying hens was determined by reversed-phase high-performance liquid chromatography. Determination of the content of lead in the serum of laying hens was performed by X-ray fluorescence analysis. The concentration of total calcium, inorganic phosphorus, and magnesium in the serum of the laying hens was determined using production kits. We detected the dose-dependent chronic effect of lead acetate on the dynamics of the content of delta-aminolevulinic acid and essential trace elements in the serum of laying hens. The administration of lead acetate into the body of productive poultry for 120 days in doses of 50, 75, and 150 mg/kg with feed did not cause visible clinical signs of poisoning, but caused a violation of porphyrin metabolism, manifested in a reliable increase in the concentration of delta-aminolevulinic acid in serum on the 30th, 90th and 120th days of the experiment. It has been experimentally proven that the administration into the body of laying hens of lead acetate in doses of 50, 75 and 150 mg/kg of feed for 120 days leads to the maximum accumulation of lead in the serum on the 30th, 90th, and 120th days of the experiment. Prolonged administration of lead acetate to laying hens at high concentrations is characterized by a reliable decrease in the content of total calcium, inorganic phosphorus and magnesium in the serum of laying hens and a reliable increase in the content of ferrum. In the future it is necessary to study the intensity of lipid peroxidation processes in laying hens under chronic exposure to lead acetate.

Biological Monitoring Among Workers Exposed to Inorganic Lead and Its Compounds

Objective: To explore the association between lead biomarkers and their deviations in the circumstances of occupational exposure, and influence of life style factors. Material and Methods: We performed cross-sectional study using 60 workers occupationally exposed to lead compared with 60 controls. All examinees were assessed by Questionnaire, and laboratory testing concerning blood lead level (BLL), activity of delta-aminolevulinic acid dehydratase (ALAD) in blood, concentration of delta-aminolevulinic acid (ALA) and coproporphyrin in urine, reticulocytes and erythrocytes with basophilic stippling (EBS). Results: The mean values of BLL and ALA were significantly higher, and mean ALAD activity was significantly lower in lead workers than in controls. Lead workers also had a higher rate of abnormal BLL, ALAD, and ALA, significant for BLL and ALAD. The average BLL values among exposed workers and controls in men were significantly higher. There was strong inverse correlation between distribution of ALAD values in exposed workers due to their BLL values. Significant correlation with mean ALAD values was shown for alcohol consumption, form of compounds, and use of protecting equipment, whereas with mean BLL values was shown for age, gender, exposure duration, smoking, and alcohol consumption. Conclusion: The data confirmed the association between occupational exposure and lead biomarkers abnormalities.

Comparison of Blood Lead and Blood and Plasma δ-Aminolevulinic Acid Concentrations as Biomarkers for Lead Poisoning in Cattle

Lead (Pb) concentrations in whole blood and δ-aminolevulinic acid (ALA) concentrations in plasma and whole blood from 37 cattle with suspected Pb exposure were determined in order to investigate the usefulness of ALA as a biological indicator for Pb poisoning in cattle. Cows were divided into 4 groups based on blood Pb, as follows: <30ppb (group 1), 30-100ppb (group 2), 100-300ppb (group 3), and >300ppb (group 4). The derivatization reaction for ALA was improved by a greater than 2-fold measure in whole blood and by a 10-fold measure in plasma by adding 75 and 50µl of 0.1N HCl, respectively. Blood Pb concentrations ranged from <25ppb to 1,006ppb (185.5 ± 254.9ppb), with 17 samples containing >50ppb Pb. Delta-aminolevulinic acid concentrations in whole blood and plasma ranged from <62.7ppb to 96.9ppb (77.4 ± 8.4ppb) and from <5.0ppb to 24.0ppb (4.6 ± 3.8ppb), respectively. Whole blood ALA did not correlate with blood lead concentrations in any group. Increase in plasma ALA concentration was dependent on blood Pb concentration. There was no correlation between blood Pb concentration and plasma ALA concentration in group 2 (n = 4), but correlation coefficients were 0.736 in group 3 and 0.807 in group 4, respectively. The correlation coefficient was increased to 0.851 when groups 3 and 4 were combined. Based on these observations, in cattle, plasma ALA is a more reliable biological biomarker for Pb exposure than is blood ALA.

Assessement of the Precursors of Heme Biosynthesis in Biological Media of Breast Cancer Patients

ISEE-0671 Background and Objective: Regulation and control of heme/porphyrin biosynthesis is very important for therapy of cancer. Some experimental studies found an increased level of protoporphyrin IX in human breast cancer cells. We tried to assess the precursors of heme biosynthesis in biological media of patients with breast cancer and benign tumour. Methods: Delta-aminolevulinic acid (delta-ALA) in urine and delta-aminolevulinic acid dehydratase (delta-ALAD) activity in blood of 57 breast cancer patients and 28 benign breast tumour patients were measured by spectrophotometry. Results: The mean delta-ALA concentration in urine was 17.16 μmol/g creatinine (95% CI = (15.15–19.16) for cancer patients and 12.86 μmol/g creatinine (95% CI = 10.65–15.07) for benign tumour patients (P = 0.01). The figures for delta-ALAD were 39.16 U/L (95% CI = 36.68–41.64) and 39.01 U/L (95% CI = 35.21–42.82), respectively (P > 0.05). Conclusion: Our findings show that heme/porphyrin biosynthesis in breast cancer patients is affected more than in benign tumour patients. The mean concentration of delta-aminolevulinic acid in urine of cancer patients is significantly higher than that in benign tumour patients.

Lead Exposure, Urinary delta-Aminolevulinic Acid Concentrations and Haematological Parameters of Road Sweepers Working in Congested Areas of Bangkok

Road sweepers are especially exposed to environmental pollution. This study investigates the lead exposure, urinary delta-aminolevulinic acid concentration (ALA) and haematological parameters of road sweepers working in traffic-congested areas of Bangkok. One hundred and ninety-four apparently healthy road sweepers aged 20-59 years were investigated. One hundred and thirty-nine staff from an academic institution served as controls. Both male and female road sweepers had slightly, but significantly, lower mean corpuscular haemoglobin concentration (MCHC) values. The white blood cell count (WBC) in female road sweepers was significantly higher compared with the female controls. The proportion of reticulocytes was higher in male and female road sweepers compared with the controls, while no difference was found in blood lead levels and ALA between male road sweepers and controls. Female road sweepers had slightly higher blood lead levels compared with the controls. ALA was no different between both groups of ...

Effects of Exposure to Lead on Selected Biochemical and Haematological Variables

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 delta-aminolevulinic acid were determined. Blood lead concentrations of the lead-exposed subjects were within the range of generally accepted as safe for occupationally-exposed adults in many countries (i.e. below 50 micrograms Pb/dl blood). Yet, significant dose-dependent elevations were found in erythrocyte GSH-peroxidase and urinary delta-aminolevulinic acid. The urinary delta-aminolevulinic acid concentration of lead-exposed smokers was significantly elevated over that of lead-exposed non-smokers. Smoking did not effect the urinary delta-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.

The effect of aluminum chloride on some steps of heme biosynthesis in rats after oral exposure.

Certain disturbances in heme biosynthesis induced by aluminum chloride were examined. The experiment was performed on female rats that received AlCl3 orally at the dose 100 mg Al/kg daily for 21 d. The effects of aluminum on the activity of delta-aminolevulinic acid synthetase (ALA-S), dehydratase (ALA-D), and heme oxygenase (O.H.) were observed on 3, 7, 14, and 21 d in liver and kidneys of rats. Also the activity of ALA-D in blood and the concentration of delta-aminolevulinic acid (ALA-U) in urine were observed. Orally administered aluminum caused increase in the activity of ALA-D in the liver and blood, and parallel decrease of ALA-U in urine (r = -0.85) of rats. Aluminum chloride also induced an increase of ALA-S and O.H. in the liver but not in the kidneys. The changes of the enzymes activity participating in heme biosynthesis after administration of aluminum may be correlated with anemia and iron metabolism in rats.

Actual status of measurement of blood concentration of lead, urinary concentration of delta-aminolevulinic acid and urinary concentration of metabolites of organic solvents entrusted to occupational health organizations

In Japan "the Regulation on the Prevention of Lead Poisoning" and "the Regulation on the Prevention of Organic Solvent Poisoning" were partially amended in 1989 to introduce biological monitoring in the special medical examinations of workers exposed to lead and 8 organic solvents (toluene, xylene, styrene, N,N-dimethylformamide, n-hexane, tetrachloroethylene, 1,1,1-trichloroethane, trichloroethylene). Since many companies entrust these medical examinations to the Occupational Health Organizations (OHOs), a survey of OHOs which collect blood and urine samples for biological monitoring was made in August 1992, to ascertain the actual status of their activities from April of 1991 to March of 1992. The following findings were obtained through this survey. 1) One hundred and eighty-six OHOs collected 129,996 blood samples to measure the concentration of lead, and the median number of samples collected per organization was 356. 2) Thirty-nine OHOs (21.0%; Group A) measured all samples in their own laboratories. The number of samples measured was 55,462 (42.7%). However, 133 OHOs (71.5%; Group B) entrusted the measurement of all samples to registered laboratories. 3) The median number of samples collected by OHOs in Group A was 1,121, and the median number of Group B was 211. 4) One hundred and eighty-three OHOs collected 126,915 urine samples to measure the concentration of delta-aminolevulinic acid and the median number of samples collected per organization was 358. 5) The blood samples as well as the urine samples were divided into three groups according to the levels of lead or delta-aminolevulinic acid concentration. The concentration is relatively low in Group 1 and relatively high in Group 3. The cut-off values for this classification are legally set in the Regulation on the Prevention of Lead Poisoning. The frequency of each group was as follows: lead (Group 1; 93.8%, Group 2; 4.9%, Group 3; 1.3%), delta-aminolevulinic acid (Group 1; 96.8%, Group 2; 3.1%, Group 3; 0.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of delta-aminolevulinic acid in blood as an indicator of lead exposure

The concentration of delta-aminolevulinic acid in blood (ALA-B) was determined using high performance liquid chromatography (HPLC). To improve the chromatographic separation and the recovery rate of ALA determination in blood, acetate buffer was used in the reaction mixture of fluorescence derivatization. The detection limit of ALA-B was ca. 2 micrograms/l at signal to noise ratio of 5, and the analytical recovery was 102.0 +/- 4.10% (mean +/- SD), when 50 micrograms/l of ALA was added to 7 blood samples (ALA-B levels: 6.5-103.0 micrograms/l). ALA-B levels in control subjects (n = 19) were 5.3 +/- 1.4 micrograms/l (mean +/- SD) and those in 52 lead workers (blood lead levels (Pb-B): 2.4-86.2 micrograms/dl) were 15.4 +/- 12.2 micrograms/l (range: 3.1-137.3 micrograms/l). Standard curve of ALA was linear over a wide range, at least up to 400 micrograms/l. In the workers, the correlation coefficients of ALA-B vs. Pb-B and ALA-B vs. delta-aminolevulinic acid dehydratase activity (ALA-D) were higher than those of urinary concentration of ALA vs. Pb-B and that vs. ALA-D, especially in the moderate Pb-B level (less than 40 micrograms/dl, n = 35). Unless the urinary concentrations of ALA were not corrected, significant correlation could not be found between Pb-B and urinary ALA in the workers moderately exposed to lead, and the correlation coefficient between urinary ALA and ALA-D was -0.354, while the correlation coefficients of ALA-B vs. Pb-B and ALA-B vs. ALA-D were 0.739 and -0.746, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A reliable method for the adjustment of urinary delta-aminolevulinic acid concentration

A reliable method for the adjustment of urinary delta-aminolevulinic acid concentration

Clinical relevance of urinary delta‐aminolevulinic acid/logarithm of creatinine ratio in screening for occupational lead exposure

Using receiver operating characteristics (ROC) analysis, the clinical relevance of urinary delta-aminolevulinic acid concentration adjusted to the logarithm of creatinine concentration (ALA/log.Cn) proved to be better than that of uncorrected ALA or ALA/Cn ratio for the detection of blood lead levels (Pb-B) exceeding 2.5, 3.0, or 3.5 mumol/l in 483 men occupationally exposed to lead. Ala/log.Cn yielded validities of 1.63, 1.75, and 1.79 at Pb-B levels 2.5, 3.0, and 3.5 mumol/l, respectively. The same values for ALA/Cn were 1.59, 1.70, 1.78 and for ALA 1.52, 1.65, 1.72, respectively. The simple adjustment to log. Cn makes urinary ALA determination more efficient in biological monitoring of the effect of occupational lead exposure.

Improved method for the adjustment of urinary delta-aminolevulinic acid concentration

The work was aimed at finding whether the ratio of delta-aminolevulinic acid (ALA) and creatinine (Cn) concentration (ALA/Cn), presently used in occupational health practice for evaluation of lead exposure gives a better assessment of ALA excretion than uncorrected ALA concentration itself, as well as at finding a better, but not complicated method for adjustment. ALA and Cn concentrations were measured in untimed urine samples of altogether 390 men and women (age: 18-60 years) not occupationally exposed to lead. In agreement with others, ALA/Cn was found to be an unsuitable method of adjustment for the differences in ALA concentration due to the different concentrations of samples. This can be explained by the different renal handling of ALA and Cn, proved by the literature data. The exponential relationship between ALA/Cn and Cn concentration raised the possibility of adjustment to the logarithm of Cn concentration (ALA/log.Cn). This simple method provided a more reliable index, the value of which was independent of the actual Cn concentration of urines within a wide range (2-32 mmol/liter). The recommended biological limit value (70 mumol/log.Cn mmol) separates equally well from normal values, both in dilute and concentrated urines. The evaluation of occupational lead exposure might be more reliable using this index, instead of uncorrected ALA concentration or the ALA/Cn ratio.

Feline Precursor. porphyria, characterized by persistent delta. Aminolevulinic aciduria

AbstractA female domestic shorthaired cat had frequent seizures and vague gastrointestinal signs. Lead poisoning was suspected because of increased urinary delta aminolevulinic acid concentration. However, abnormalities continued despite repeated chelation therapy and blood lead concentration was normal. Delta aminolevulinic aciduria persisted, but concentrations of porphobilinogen in urine and of porphyrins in blood, urine and faeces were normal. An inherited porphyric disorder was suspected, involving deficiency of aminolevulinic acid dehydrase, an enzyme active in haem biosynthesis. Accumulation of aminolevulinic acid in vivo could explain the observed signs.

Structural discrimination in the sparking function of sterols in the yeast Saccharomyces cerevisiae.

A Saccharomyces cerevisiae sterol auxotroph, SPK14 (a hem1 erg6 erg7 ura), was constructed to test the ability of selected C-5,6 unsaturated sterols at growth-limiting concentrations to spark growth on bulk cholestanol. The native sterol, ergosterol, initiated growth faster and allowed a greater cell yield than did other sterols selectively altered in one or more features of the sterol. Although the C-5,6 unsaturation is required for the sparking function, the presence of the C-22 unsaturation was found to facilitate sparking far better than did the C-7 unsaturation, whereas the C-24 methyl was the least important group. The addition of delta-aminolevulinic acid to the medium allowed the sparking of FY3 (hem1 erg7 ura) on bulk cholestanol due to the derepression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and the production of endogenous ergosterol. The optimal concentration of delta-aminolevulinic acid to spark growth was 800 ng/ml, whereas higher concentrations caused a growth inhibition. The growth yield of FY3 reached a plateau maximum at about 5 micrograms/ml when the bulk cholestanol was varied in the presence of 10 ng of sparking erogosterol per ml.

Clinical evaluation on 5 cases of lead Poisoning

5 cases of lead poisoning were investigated clinically. Of the 5 patients, 4 were male and 1 was female. The causes of lead poisoning in 3 cases were ingestion of herb drug pills and in 2 cases were occupational poisoning. Chief complain at admission in 4 cases were in defined colicky abdominal pain and constipation. Only 1 case complained of dizziness and palpitation without gastrointestinal symptom. On peripheral blood, normocytic normochromic anemia (mean Hgb 9.2gm/dl), reticulocytosis (mean 4.7%) and basophilic stippling were found in 100% of patients. Bone marrow aspiration was done in 4 cases. Erythroid hyperplasia and basophilic stippling were found in all 4 cases. Mean M : E ratio was 0.7 : 1. The lead concentration in serum was in creased in 4 cases (80%) of patients. Lead concentration, deltaaminolevulinic acid concentration in 24 hours collected urine were in creased in 5 patients (100%). Qualitative test of coproporphyrin of urine was positive in all 5 cases. 3 patients treated with Ca-EDTA, abdominal pain was improved rapidly and hemoglobin level was in creased slowly.

Evaluation of tests for the diagnosis of lead exposure in sheep.

Several laboratory tests that are currently used for the diagnosis of lead poisoning in man were evaluated for the detection of lead poisoning in sheep given 3 or 10 mg Pb/kg body weight/day for 7 weeks. Urinary porphyrins and basophilic stippling of erythrocytes were not sensitive indicators of lead poisoning in sheep, while urinary lead and urinary delta-aminolevulinic acid concentrations were too variable to have diagnostic value. However, erythrocyte delta-aminolevulinic acid dehydratase was strongly inhibited by exposure to relatively low doses of lead, while blood lead concentrations gave an indication of the level of exposure to lead poisoning.

Impact of air pollution by lead on the heme biosynthetic pathway in school-age children.

Blood-lead level (Pb-B), erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, delta-aminolevulinic acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10-13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10-40 mug/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a significant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men. Based on the FEP response, it is proposed that 25 mug Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.

Effect of cobalt on synthesis of heme and cytochrome P-450 in the liver. Studies of adult rat hepatocytes in primary monolayer culture and in vivo.

Synthesis of heme and cytochrome P-450 have been studied in adult rat hepatocytes in primary monolayer culture. Incubation of cells with delta-aminolevulinic acid increases both cellular heme and cytochrome P-450 relative to that found in cells incubated under control conditions. Formation of heme is proportional to the concentration of delta-aminolevulinic acid in the culture medium and is not saturable. By contrast, formation of cytochrome P-450 is saturable; excess intracellular heme appears as a new absorption band at 420 nm in the carbon monoxide-reduced difference spectrum. We have studied the effect of cobalt on heme and hemoprotein formation in this cell system. The metal blocks formation of cytochrome P-450 but fails to affect heme synthesis. In contrast to previous findings with isolated mitochondria, no cobalt protoporphyrin formed in hepatocytes cultured in the presence of the metal. In studies of rats in vivo, it was confirmed that cobalt acts to reduce the amount of [14C]heme in the liver after administration of delta-amino[14C]levulinic acid. However, the present findings suggest that this effect of cobalt represents accelerated breakdown of newly labeled hepatic heme rather than inhibition of synthesis. We conclude that cobalt interferes with formation of cytochrome P-450 not by direct inhibition of heme synthesis but most likely by blocking the association of heme and apocytochrome.

INTERRELATIONSHIPS OF SOME. BIOCHEMICAL INDICATORS OF LEAD ABSORPTION WITH SPECIAL REFERENCE TO SERUM DELTA-AMINOLEVULINIC ACID AND ITS RENAL CLEARANCE

Some biological indicators of lead absorption from 23 lead smelters were examined three times. By an accidental a month's discontinuation of exposure, mean concentra-tions of coproporpyrin and delta-aminolevulinic acid in urine decreased to one third, and also positive rates of subjective complaints to one half, but hemoglobin content, stippled cells, polychromatic cells, reticulocytes and lead concentration showed much less improvement. Factor analysis of the indicators revealed the concentration of coproporphyrin in urine had a very different character among them. Ninety three percent of the data matrix of them were explained by the four factors. Mean con-centration of delta-aminolevulinic acid in serum was 35.5±11.4μg/d1 and renal clear-ance and renal reabsorption rate of the substance was 11.2 to 16.9 ml/min and 92.5 to 97.5%, respectively, concerning the six admitted smelters except one case. Concentra-tion of delta-aminolevulinic acid in serum will never be so an excellent indicators, but may be a key substance of delta-aminolevulinic acid and coproporphyrin excretion to urine.