Effects of lead on lactating rats and their sucklings

Lead was administered to lactating rats in drinking water (0, 1, 10 and 100 ppm) from the day of delivery up to day 21 after delivery, at which time the mothers and their newborns were sacrificed. Various parameters of blood: lead concentration (PbB), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrin concentration (FEP), δ-aminolevulinate dehydratase activity (ALAD) — and of tissue: ALAD activity, free tissue porphyrin concentration (FTP) and lead concentration (PbT) were determined.In mothers, a significant increase of PbB and a reduction in ALAD activity of blood were found in the 100 ppm group. In tissues Pb was significantly increased in liver of the 100 ppm group and in kidney of the 10 and 100 ppm groups. None of the biochemical parameters measured in tissues was significantly modified.In suckling rats an increase in PbB and a reduction of ALAD activity in blood were found in the 10 and 100 ppm lead groups. Pb concentration was significantly increased in liver, kidney and brain of the 100 ppm group and in kidney of the 10 ppm group. Lead storage in kidney of the 100 ppm group was associated with a marked increase in FTP and a slight reduction in ALAD activity.On the basis of the biochemical parameters studied in the newborn rats, the “no-effect” level of lead administered in drinking water during lactation is around 1 ppm, which is rather similar to that found when lead was administered to the mother before and/or during pregnancy.     

Effect of lead on some parameters of the heme biosynthetic pathway in rat tissues in vivo

Lead was administered to male and female rats in drinking water for 3 and 6 weeks at the following doses: 0, 10, 100, 1000, 5000 ppm and for 6 months at 10 ppm only. Various parameters of blood-lead concentration (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEP), δ-aminolevulinate dehydratase (AlAD), reticulocytes- and tissu-ALAD, free tissue pophyrins (FTP), lead concentration (Pb-T)-were determined. Pb-B incrases with dose but reaches rapidly a plateau despite continuous Pb administration.Concentratoni of Pb in kidney, liver and brain correlates with Pb-B. Pb does not accumulate in heart. Kidney is the main site of Pb deposition and kidney ALAD is the parameter most susceptible to lead, since reduction is observed in all treated groups after 3 weeks of exposure.However, kidney ALAD inhibition in transitory since after 6 weeks it is only observed in the 5000 ppm group. At 10 ppm lead prevents also the increase in blood ALAD activity normally associated with the reticulocytosis of repetitive bleeding. The next parameters affected by lead are: ALAD in blood which in inhibited after 6 weeks of treatment with 100 ppm lead, and FEP, α-aminolevulinic acid plus other pyrrole-forming substances in urine (ALA-U), and FTP inkidney which are increased after 3 or 6 weeks of treatment with 100 and 5000 ppm lead.     

A polymorphism in the delta-aminolevulinic acid dehydratase gene modifies plasma/whole blood lead ratio

Delta aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning. This study was carried out to examine the effects of ALAD gene polymorphism (G177C) on %Pb-P(plasma lead)/Pb-B(whole blood) ratio in 142 subjects environmentally exposed to lead. Genotypes for the ALAD G177C polymorphism were determined by PCR and restriction fragment length digestion. Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. The allele frequencies for ALAD1 and ALAD2 alleles were 0.897 and 0.103, respectively. We combined both ALAD 1-2 and ALAD 2-2 genotypes together (ALAD 1-2/2-2 group) and compared with the ALAD 1-1 genotype group. While no significant differences were found in Pb-B, subjects from the ALAD 1-2/2-2 genotype group presented significantly higher Pb-P concentrations and %Pb-P/Pb-B ratios (0.89±0.07 μg/l, and 1.45±0.10%, respectively) when compared with subjects from the ALAD 1-1 genotype group (0.44±0.05 μg/l, and 0.48±0.02, respectively; both P<0.0001). The higher %Pb-P/Pb-B ratios in carriers of the ALAD-2 allele compared with noncarriers indicate that ALAD 1-2/2-2 subjects are probably at increased health risks associated with lead exposure.     

Assessment of how pregnancy modifies plasma lead and plasma/whole blood lead ratio in ALAD 1-1 genotype women

Pregnant women are one of the most sensitive populations to the toxic effects associated with lead (Pb) exposure. These effects are primarily associated with plasma Pb (Pb-P), which reflects the most rapidly exchangeable fraction of Pb in the bloodstream, and elevated maternal Pb-P may be more relevant to foetal Pb exposure than whole blood Pb (Pb-B). We investigated how pregnancy affects Pb-B, Pb-P and %Pb-P/Pb-B ratios without the influence of the delta-aminolevulinic acid dehydratase (ALAD) G177C polymorphism, which is a major genetic factor influencing Pb-B, Pb-P and %Pb-P/Pb-B ratios. Genotypes for the ALAD G177C polymorphism were determined by PCR and restriction fragment length digestion in nine pregnant and 20 non-pregnant women, aged 18-33, environmentally exposed to Pb. Here, we included only women with ALAD 1-1 genotype. Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. We found no differences in Pb-B (P > 0.05). However, pregnant women had a 2-fold increase in Pb-P and a 3-fold increase in %Pb-P/Pb-B (both P < 0.01) compared to non-pregnant women. These alterations in Pb concentrations associated with pregnancy are similar to those associated with different ALAD gene variants. We can now better appreciate how pregnancy affects foetal exposure to Pb without the influence of this important genetic factor.     

Environmental lead exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in maternal and cord blood.

The hypothesis that environmental lead exposure measured from blood (Pb-B) inhibits delta-aminolevulinic acid dehydratase activity (ALA-D) from whole blood was tested in 241 urban mothers and their newborns. Geometric means and (5th and 95th Percentiles) for maternal and cord Pb-B were 6.4 microg dl(-1) (3.4-11.9) and 4.6 microg dl(-1) (2.8-9.2). Spearman correlations between mother and cord Pb-B and ALA-D were all negative but statistically significant only for cord Pb-B and mother ALA-D. A potential lead threshold, was identified between 3.2 and 4.8 microg dl(-1), above which ALA-D may be inhibited by lead, and below which ALA-D may be insensitive or even activated. In conclusion, low environmental exposure to lead is responsible for a demonstrable biochemical effect. This potential ALA-D inhibition may lead to neurotoxic effects, especially in newborns who have high level of neurogenesis.     

Genetic variability in the system of natriuretic B peptide and principal toxicological parameters in workers exposed to lead

The study was aimed at evaluating the influence of selected polymorphisms of natriuretic peptide B precursor (NPPB) and natriuretic peptide receptor C (NPR3) genes on blood lead concentration (Pb-B) and blood zinc protoporphyrin concentration (ZnPP) in persons occupationally exposed to lead. Investigations were conducted on 360 persons (mean age: 44.49 ± 9.62 years), workers exposed to lead compounds. The analysis examined four polymorphisms of BNP gene, i.e.,: rs198388, rs198389, rs632793, and rs6676300; as well as one polymorphism of receptor C for natriuretic peptides, i.e., rs1421811. Heterozygosity in locus rs632793 of NPPB gene may result in higher concentrations of Pb-B, while allele A in locus rs632793 of NPPB gene seems to determine higher concentrations of ZnPP in persons occupationally exposed to lead. Workers exposed to lead and carrying allele C in locus rs198388 of NPPB gene, particularly in the heterozygotic setup, seem to be predisposed to present higher concentrations of ZnPP. Carriership of A allele in locus rs198389 of NPPB gene probably determines higher concentrations of ZnPP in study group. In summary, among persons occupationally exposed to lead, certain relationships were demonstrated between rs632793, rs198388 and rs198389 polymorphisms of NPPB gene and principal toxicological parameters characterizing exposure to lead.     

Association between delta-aminolevulinic acid dehydratase polymorphism and placental lead levels

Lead inhibits the delta-aminolevulinic acid dehydratase (ALAD) activity and results in neurotoxic aminolevulinic acid accumulation in the blood. During pregnancy, lead in the maternal blood can easily cross the placenta. The aim of this study was to determine whether the maternal ALAD G177C polymorphism (rs1800435) was related to the placental lead levels. The study population comprised 97 blood samples taken from mothers to investigate ALAD G177C polymorphism and their placentas to measure lead levels. ALAD G177C polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique and atomic absorption spectrometry (AAS) equipped with a graphite furnace and Zeeman background correction system was used for lead determination. The median placental lead levels for ALAD1-1, ALAD1-2 and ALAD2-2 genotypes were 7.54 μg/kg, 11.78 μg/kg and 18.53 μg/kg, respectively. Statistically significant association was found between the maternal ALAD G177C polymorphism and placental lead levels (p < 0.05). This study suggested that maternal ALAD G177C polymorphism was associated with placental lead levels.     

Effect of Centella asiatica on arsenic induced oxidative stress and metal distribution in rats

Concomitant oral supplementation of Centella asiatica (100, 200 or 300 mg kg(-1), orally once daily) during arsenic exposure (20 ppm in drinking water for 4 weeks) was investigated in rats for its protective value. The animals exposed to arsenic (III) showed a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity, a marginal decrease in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) level in blood. Hepatic and renal glutathione (GSH) decreased, while oxidized glutathione (GSSG) and thiobarbituric acid reactive substance (TBARS) levels increased significantly in the liver, kidney and brain. The activities of brain superoxide dismutase (SOD) and catalase decreased marginally on arsenic exposure. Concomitant administration of Centella asiatica showed a significant protective action on inhibited blood ALAD activity and restored the blood GSH level, whereas most of the other blood biochemical parameters remained unchanged on Centella asiatica supplementation. Interestingly, most of the hepatic biochemical variables indicative of oxidative stress showed protection. There was, however, a significant protection observed in the altered kidney GSSG level and hepatic and brain TBARS. Only a marginal beneficial effect of Centella asiatica on blood and liver arsenic concentration was noted, particularly at the highest dose studies (300 mg kg(-1)). No effect of Centella asiatica on most of the altered renal biochemical parameters was noted. The results thus lead to the conclusion that simultaneous supplementation of Centella asiatica significantly protects against arsenic-induced oxidative stress but does not influence the arsenic concentration in these organs. It can thus be suggested that co-administration of Centella asiatica protects animals from arsenic-induced oxidative stress but exhibits no chelating property. Further studies are recommended for determining the effect of co-administration of Centella asiatica during chelation therapy with a thiol chelator.     

Function of respiratory system evaluated using selected spirometry parameters in persons occupationally exposed to lead without evident health problems

This study aimed at evaluation of selected spirometric parameters in persons occupationally exposed to lead without evident health problems. The studies were conducted on 69 men occupationally exposed to lead. Occupational exposure to lead was characterized by estimation of blood lead concentration (Pb-B) and blood zinc protoporphyrin concentration (ZnPP). Function of respiratory system was examined using spirometric analysis with evaluation of its basic parameters: forced vital capacity (FVC), forced expiratory volume (in 1 s) (FEV1), Tiffeneau index (FEV1%VC) and peak expiratory flow (PEF). In the study group negative linear correlations were documented between Pb-B and FVC, FEV 1 and FEV1%VC. A more pronounced age, higher values of BMI and higher blood lead concentration constituted independent risk factors for reduced FEV1%VC.ConclusionPersons occupationally exposed to lead with elevated blood lead concentration and blood zinc protoporphyrin concentration manifested the impaired function of respiratory system, evaluated using parameters of spirometry.     

Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats

We investigated the therapeutic efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) and two of its analogues, monomethyl dimercaptosuccinic acid (MmDMSA) and mono-cyclohexyl dimercaptosuccinic acid (MchDMSA) in reducing lead concentration in blood and soft tissues, and in recovering lead induced oxidative stress in rats. Male wistar rats were exposed to lead acetate in drinking water for 20 weeks, followed by 5 days of oral treatment with DMSA (100mg/kg, oral, once daily), MmDMSA or MchDMSA (50 and 100mg/kg). Biochemical variables indicative of oxidative stress along with lead, zinc and copper concentration were evaluated in blood and other soft tissues. Exposure to lead caused a significant decrease in blood delta-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by inhibition of kidney ALAD and an increase in delta-aminolevulinic acid synthatase (ALAS) activity in liver and kidneys. Also seen were a pronounced depletion of brain GSH, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and decreased superoxide dismutase (SOD) activity and an increase in thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) levels. These biochemical changes were correlated with an increased uptake of lead in blood and soft tissues. Blood and kidneys zinc concentration decreased significantly following lead exposure while, copper concentration remained unchanged. No effect of chelation on hepatic zinc concentration was noted, only liver copper concentration showed significant depletion on treatment with DMSA and MmDMSA (100mg/kg). Treatment with DMSA, MmDMSA and MchDMSA provided significant recovery in altered biochemical variables and brain DNA damage besides significant depletion of tissue lead burden. Among the chelating agents used, MchDMSA and MmDMSA provided better recovery in altered biochemical variables and depletion of lead concentration in tissues compared to DMSA. The above results suggest DMSA monoesters to be a better treatment option than DMSA in eliciting recovery to the altered biochemical variables and in the depletion of body lead burden.     

Combined administration of taurine and meso 2,3-dimercaptosuccinic acid in the treatment of chronic lead intoxication in rats

The present study describes the dose-dependent effect of taurine, an amino acid and a known antioxidant, either alone or in combination with meso 2,3-dimercaptosuccinic acid (DMSA) in the treatment of subchronic lead intoxication in male rats. The effects of these treatments in influencing the lead-induced alterations in haem synthesis, hepatic, renal or brain oxidative stress and lead concentration from soft tissues were investigated. Exposure to lead produced a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity, reduction in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) suggesting an altered haem synthesis pathway. Only DMSA was able to increase the activity of ALAD, while both taurine and DMSA were able to significantly increase GSH level towards normal. Animals treated with taurine significantly reduced the alterations in some of the biochemical parameters indicative of oxidative stress. Thiobarbituric acid reactive substance (TBARS) levels reduced significantly in liver, kidney and red blood cells, while GSH level increased. Activity of superoxide dismutase (SOD) also showed an increase in blood and brain in animals treated with taurine. The data also provided a promising role of taurine during chelation of lead by potentiating the depletion of blood, liver and brain lead compared to DMSA alone. It can thus be concluded from the study that concomitant administration of an antioxidant could play a significant and important role in abating a number of toxic effects of lead when administered along with the thiol chelators.     

Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats

Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree; Hindi: Saijan; Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. Besides, the plant is reported to have various biological activities, including hypocholesterolemic agent, regulation of thyroid hormone status, anti-diabetic agent, gastric ulcers, anti-tumor agent and hypotensive agent, used for treating various diseases such as inflammation, cardiovascular and liver diseases. Therapeutic efficacy of oral administration of seed powder of M. oleifera (500 mg/kg, orally, once daily) post arsenic exposure (100 ppm in drinking water for 4 months) was investigated in rats. Animals exposed to arsenic(III) showed a significant inhibition of δ-aminolevulinic acid dehydratase (ALAD) activity, decrease in reduced glutathione (GSH) level and an increase in reactive oxygen species (ROS) in blood. On the other hand, a significant decrease in hepatic ALAD, and an increase in δ-aminolevulinic acid synthetase (ALAS) activity was noted after arsenic exposure. These changes were accompanied by an increase in thiobarbiturc acid reactive substances (TBARS) level in liver and kidney. Activities of liver, kidney and brain superoxide dismutase (SOD) and catalase also showed a decrease on arsenic exposure. Administration of M. oleifera seed powder post arsenic exposure, exhibited significant recovery in blood ALAD activity while, it restored blood GSH and ROS levels. Most of the other blood biochemical variables remained unchanged on M. oleifera supplementation. A significant protection in the altered ALAD and ALAS activities of liver and TBARS level in liver and kidney was however, observed after M. oleifera administration. Interestingly, there was a marginal but significant depletion of arsenic from blood, liver and kidneys. The results, thus lead us to conclude that post arsenic exposure administration with the seed powder of M. oleifera has significant role in protecting animals from arsenic-induced oxidative stress and in the depletion of arsenic concentration. Further studies thus can be recommended for determining the effect of co-administrating seed powder of M. oleifera during chelation therapy with a thiol chelator.     

Changes in low levels of lead over the course of pregnancy and the association with birth outcomes

Data are lacking on the effect of low level prenatal lead exposure. We examined the change in blood lead from the second trimester until delivery and the association between maternal and cord blood lead and birth outcomes in 98 participants of the CANDLE birth cohort study. Mixed effects models were constructed to assess blood lead change over pregnancy and regression models were used to explore the relationship with cord blood lead, characteristics effecting maternal lead, birth weight and gestational age. Overall, the geometric mean maternal blood level was 0.43 μg/dL. Maternal blood lead at each time point was predictive of cord blood lead level. A 0.1 μg/dL increase in second trimester lead was associated with lower birth weight and pre-term birth. Maternal blood lead below 1 μg/dL behaves in a manner similar to lead at higher levels and is associated with a small decrease in birth weight and gestational age.     

Environmental lead exposure induces changes in the heme biosynthetic pathway

Lead is ubiquitous in the environment today. Lead enters our body from a variety of sources such as urban environments and food. All humans have lead in their bodies primarily as a result of exposure to man-made sources. Children show a greater sensitivity to lead's effects than adults do. In this study, the concentration of metabolites of heme biosynthesis in school children from a group of volunteers with various blood lead contents and a group of lead-intoxicated children were reported. Also, the measurement of free erythrocyte porphyrins (FEP) as a microscreening test for lead toxicity was performed, and the blood lead levels of the school children were determined as well. The results show that the concentrations of the metabolites of heme biosynthesis are affected by the blood lead level. FEP level shows a small change as the blood lead level slightly increases. Elevation of blood lead level and the increase of the metabolite concentration are a good indication of lead-induced heme metabolic changes. FEP is an excellent screening test for the heme metabolic imbalances. Because of differences in individual susceptibility, symptoms of lead intoxication and their onset may vary. With increasing exposure, the severity of symptoms can be expected to change with varying degrees of lead toxicity. ©1997 by John Wiley & Sons, Inc. Environ Toxicol Water Qual 12 : 245–248, 1997     

Developmental toxicity of lead-contaminated sediment in Canada geese (Branta canadensis)

Sediment ingestion has recently been identified as an important exposure route for toxicants in waterfowl. The effects of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho on posthatching development of Canada geese (Branta canadensis) were examined for 6 wk. Day-old goslings received either untreated control diet, clean sediment (48%) supplemented control diet, or CDARB sediment (3449 microg/g lead) supplemented diets at 12%, 24%, or 48%. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 0.68 ppm (ww), with over 90% depression of red blood cell ALAD activity and over fourfold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 1.61 ppm with decreased hematocrit, hemoglobin, and plasma protein in addition to the effects just described. The 48% CDARB diet resulted in blood lead of 2.52 ppm with 22% mortality, decreased growth, and elevated plasma lactate dehydrogenase-L (LDH-L) activity. In this group the liver lead concentration was 6.57 ppm (ww), with twofold increases in hepatic lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) and in reduced glutathione concentration; associated effects included elevated glutathione reductase activity but lower protein-bound thiols concentration and glucose-6-phosphate dehydrogenase (G-6-PDH) activity. The kidney lead concentration in this group was 14.93 ppm with subacute renal tubular nephrosis in one of the surviving goslings. Three other geese in this treatment group exhibited calcified areas of marrow, and one of these displayed severe chronic fibrosing pancreatitis. Lead from CDARB sediment accumulated less readily in gosling blood and tissues than reported in ducklings but at given concentrations was generally more toxic to goslings. Many of these effects were similar to those reported in wild geese and mallards within the Coeur d'Alene River Basin.     

Nephrotoxicity induced by chromium (VI) in adult rats and their progeny

To assess kidney damages in pregnant and lactating rats and in their suckling pups, Wistar female rats were given, through drinking water, 700 parts per million (ppm) of K(2)Cr(2)O(7) from the 14th day of pregnancy until day 14 after delivery. Toxicity was objectified by a significant increase in malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) levels in kidney of chromium-treated mothers and their suckling pups. Moreover, lactate dehydrogenase (LDH) was increased in kidney and decreased in plasma of K(2)Cr(2)O(7)-treated rats. Activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were increased in dams and decreased in their pups. Interestingly, these biochemical modifications were accompanied by higher plasma and lower urinary levels of creatinine, a specific indicator of glomerular function, and of urea than those of controls. Significant increase in creatinine clearance was also found in treated mothers and in their progeny. Histological studies showed an infiltration of mononuclear cells, necrosis and vascular congestion in kidney of pups and dams. Based on the present findings, K(2)Cr(2)O(7) administrated to female rats during late pregnancy and early postnatal periods provoked kidney damages in dams and their offspring.     

DEVELOPMENTAL TOXICITY OF LEAD-CONTAMINATED SEDIMENT IN CANADA GEESE (Branta canadensis)

Sediment ingestion has recently been identified as an important exposure route for toxicants in waterfowl. The effects of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho on posthatching development of Canada geese (Branta canadensis) were examined for 6 wk. Day-old goslings received either untreated control diet, clean sediment (48%) supplemented control diet, or CDARB sediment (3449 mug/g lead) supplemented diets at 12%, 24%, or 48%. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 0.68 ppm (ww), with over 90% depression of red blood cell ALAD activity and over fourfold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 1.61 ppm with decreased hematocrit, hemoglobin, and plasma protein in addition to the effects just described. The 48% CDARB diet resulted in blood lead of 2.52 ppm with 22% mortality, decreased growth, and elevated plasma lactate dehydrogenase-L (LDH-L) activity. In this group the liver lead concentration was 6.57 ppm (ww), with twofold increases in hepatic lipid peroxidation (thiobarbituric acid-reactive substances, TBARS) and in reduced glutathione concentration; associated effects included elevated glutathione reductase activity but lower protein-bound thiols concentration and glucose-6-phosphate dehydrogenase (G-6-PDH) activity. The kidney lead concentration in this group was 14.93 ppm with subacute renal tubular nephrosis in one of the surviving goslings. Three other geese in this treatment group exhibited calcified areas of marrow, and one of these displayed severe chronic fibrosing pancreatitis. Lead from CDARB sediment accumulated less readily in gosling blood and tissues than reported in ducklings but at given concentrations was generally more toxic to goslings. Many of these effects were similar to those reported in wild geese and mallards within the Coeur d'Alene River Basin.     

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.     

Effects of perinatal treatment with lead and disulfiram on ALAD activity in blood, liver and kidney and urinary ALA excretion in rats

Disulfiram, which is metabolized to diethyldithiocarbamate, is known to greatly influence the tissue distribution of lead (Pb) and potentiate the toxic effect of lead in the central nervous system. Effects on delta-aminolevulinic acid dehydratase (ALAD) activity and urinary delta-aminolevulinic acid (ALA) excretion were studied in rats pre- and postnatally exposed to lead and disulfiram, singly or in combination. Pregnant rats were treated with lead (0.25% Pb in the drinking water), with disulfiram (0.1 mmol/kg orally twice a week) or with both lead and disulfiram from day 1 of pregnancy until weaning. After parturition the disulfiram was given subcutaneously directly to the offspring. ALAD activity in blood was inhibited to a similar extent in the group treated with lead alone and in the group treated with lead and disulfiram (7 and 10% of control activity, respectively). Liver and kidney ALAD activities were not affected by the combined treatment with lead and disulfiram. However, urinary excretion of ALA was increased twice as much in the group treated with lead and disulfiram as in the group treated with only lead. The haematocrits were also significantly more depressed after combined exposure to lead and disulfiram. Two weeks after cessation of exposure ALAD activity in blood was inhibited to 47% of control activity in both the lead- and the lead plus disulfiram-treated groups. At this time there was no effect due to treatment on urinary ALA excretion of haematocrit. The results indicate that disulfiram probably influences the effects of lead on ALAD activity at the site of haem synthesis in the bone marrow.2+t is     

Haplotypes of vitamin D receptor modulate the circulating levels of lead in exposed subjects

Genetic factors influence whole blood lead (Pb-B) concentrations in lead exposed subjects. This study aimed at examining the combined effects (haplotype analysis) of three polymorphisms (BsmI, ApaI and FokI) in vitamin D receptor (VDR) gene on Pb-B and on the concentrations of lead in plasma (Pb-P), which is more relevant to lead toxicity, in 150 environmentally exposed subjects. Genotypes were determined by RFLP, and Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. Subjects with the bb (BsmI polymorphism) or ff (FokI polymorphism) genotypes have lower B-Pb than subjects in the other genotype groups. Subjects with the aa (ApaI polymorphism) or ff genotypes have lower P-Pb than subjects in the other genotype groups. Lower Pb-P, Pb-B, and %Pb-P/Pb-B levels were found in subjects with the haplotype combining the a, b, and f alleles for the ApaI, BsmI, and FokI polymorphisms, respectively, compared with the other haplotype groups, thus suggesting that VDR haplotypes modulate the circulating levels of lead in exposed subjects.