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Showing papers on "Lead acetate published in 1999"


Journal ArticleDOI
TL;DR: The beneficial effects of high-dose vitamin E on blood pressure, tissue nitrotyrosine burden, and urinary NOx excretion support the role of increased ROS activity in the pathogenesis of these abnormalities in this model.

229 citations


Journal ArticleDOI
TL;DR: Results suggest that lead may induce DNA damage through a Fenton‐like reaction and that singlet oxygen is the principal species involved.
Abstract: To investigate DNA damage induced by Pb2+ and its prevention by scavengers, we determined DNA strand breakage and the formation of 8-hydroxydeoxyguanosine (8-OHdG) in DNA using plasmid relaxation assay and HPLC with electrochemical detection, respectively. Lead acetate induced DNA strand breakage in 10 mM of Hepes buffer, pH 6.8, in a time- and dose-dependent manner. Compared with lead, zinc acetate did not significantly induce DNA breakage. The singlet oxygen scavengers NaN3 and 2,2,6,6-tetramethyl-4-piperidone (TEMP) inhibited lead-induced DNA breakage more efficiently than the hydroxyl radical scavengers mannitol and DMPO. Deuterium oxide (D2O), a singlet oxygen enhancer, potentiated lead-induced DNA breakage. At low ratios to Pb2+, NADPH, glutathione, and 2-mercaptoethanol enhanced lead-induced DNA breakage, whereas high ratios of these agents protected it. Catalase and superoxide dismutase (SOD) did not protect DNA breaks induced by Pb2+. Lead-induced DNA breakage was markedly enhanced by H2O2, and this induction was inhibited by NaN3, TEMP, EDTA, catalase, BSA, and glutathione. In contrast, mannitol and SOD potentiated Pb2+/H2O2-induced DNA breaks. The results indicate that singlet oxygen, lead, and H2O2 are all involved in the reaction system, whereas hydroxyl radical and superoxide did not. Lead could cause a small amount of 8-OHdG formation in calf thymus DNA and dose-dependently induced the formation of this adduct in the presence of H2O2. Singlet oxygen scavengers were more effective than hydroxyl radical scavengers in protection from lead/H2O2-induced 8-OHdG adducts. Taken together, these results suggest that lead may induce DNA damage through a Fenton-like reaction and that singlet oxygen is the principal species involved. Environ. Mol. Mutagen. 33:194–201, 1999 © 1999 Wiley-Liss, Inc.

87 citations


Journal ArticleDOI
TL;DR: The results suggest that DMSA reverses some of the lead-induced immunotoxicity; however, this treatment itself during embryonic development produces subsequent adult immunomodulation.

54 citations


Journal ArticleDOI
TL;DR: Observations reflect the complexity of lead's nephrotoxicity and endorse the application of proteomics in mechanistic studies as well as biomarker development in a variety of toxicologic paradigms.
Abstract: Lead is a potent neuro- and nephrotoxin in humans and a renal carcinogen in rats. Previous studies have detected lead-induced increases in the activities of specific detoxification enzymes in distinct kidney cell types preceding irreversible renal damage. While preferential susceptibility of the highly vascularized cortex to the effects of lead is clear, lead effects on the medullary region have remained unexplored. The present study was undertaken to investigate the extent to which regional renal protein expression differs and to determine which, if any, regionally distinct protein markers indicative of lead's renotoxic mechanism might be detected in kidney cortical and medullary cytosols. We examined protein expression in these two functionally and anatomically distinct regions, and identified several proteins that are differentially expressed in those regions and were significantly altered by lead. Kidney cytosols from rats injected with lead acetate (114 mg/kg, three consecutive daily injections) were separated by two-dimensional electrophoresis. Lead exposure significantly (P<0.001) altered the abundance (either or) of 76 proteins in the cortex and only 13 in the medulla. Eleven of the proteins altered in the protein patterns were conclusively identified either by matrix-assisted laser desorption/ionization mass spectrometry/electrospray ionization-mass spectrometry (MALDI-MS/ESI-MS) analysis of peptide digests, immunological methods, or by gel matching. Several of the cortical proteins altered by lead were unchanged in the medulla while others underwent similar but lesser alterations. These observations reflect the complexity of lead's nephrotoxicity and endorse the application of proteomics in mechanistic studies as well as biomarker development in a variety of toxicologic paradigms.

54 citations


Journal ArticleDOI
TL;DR: Autoradiographic analysis of brain sections indicated that Pb-exposure did produce a decrease in [125I]sulpride (D2 receptor antagonist) binding in the cerebral cortex, but not in the striatum and thalamus nucleus, and it is possible that P b-related change in D2 receptors may mediate to it induced hyperlocomotor activity.

52 citations


Journal ArticleDOI
TL;DR: Data suggest that brain catalase is involved in ethanol's effects and provide further support for the notion that acetaldehyde may be produced directly in the brain viaCatalase and that it may be a factor mediating some of ethanol's central effects.
Abstract: It has been proposed that brain catalase plays a role in the modulation of some psychopharmacological effects of ethanol. The acute administration of lead acetate has demonstrated a transient increase in several antioxidant cell mechanisms, including catalase. In the present study, we investigated the effects of acute lead acetate administration on ethanol-induced behavior, brain catalase activity, and the relation between both effects. Lead acetate (100 mg/kg) or saline was injected intraperitoncally in mice. At different intervals of time (1, 3, 5, 7, 9, or 11 days) after this treatment, ethanol (2.5 g/kg) was injected intraperitoneally and the mice were placed in open field chambers. Results indicated that the locomotor activity induced by ethanol was significantly increased. Maximum ethanol-induced locomotion increase (70% more activity than control animals) was found in animals treated with lead acetate 7 days before ethanol administration. Total brain catalase activity in lead-pretreated animals also showed a significant induction, which was maximum 7 days after lead administration. A significant correlation was found between both effects of locomotor and catalase activity. In a second study, the effect of lead administration on d-amphetamine (2.0 mg/kg) and tert-butanol-(0.5 g/kg) induced locomotor activity was investigated. Lead acetate treatment did not affect the locomotion induced by these drugs. These data suggest that brain catalase is involved in ethanol's effects. They also provide further support for the notion that acetaldehyde may be produced directly in the brain via catalase and that it may be a factor mediating some of ethanol's central effects.

46 citations


Journal ArticleDOI
01 Aug 1999-Alcohol
TL;DR: The fact that brain catalase and ethanol-induced locomotor activity followed a similar pattern could suggest a relationship between both lead acetate effects and also a role for brainCatalase in ethanol- induced behaviors.

44 citations


Journal ArticleDOI
TL;DR: The possibility that early exposure to low doses of lead during development is capable of enhancing aggressive behavior in males is supported, because lead-exposed male hamsters were faster and more likely to attack and bite their intruders.

43 citations


Journal ArticleDOI
TL;DR: It is demonstrated that low-level lead exposure could reduce the range of synaptic plasticity, which might underlie the dysfunction of learning and memory caused by chronic lead exposure.

34 citations


Journal ArticleDOI
TL;DR: An inhalation model used to identify the possible lung cell damage after exposure of animals to Pb showed increased concentrations of Pb and other metals in human autopsied lungs when comparing a thirty-year period of the records of people who lived in Mexico City during the 1950’s to those of the ones who live in the same city but in the 1980s.
Abstract: Fortoul, T. I . , R. C. Salgado, S. G. Moncada, I. G. Sanchez, I. E. Lopez, G. Espejel, N. L. Calderon, L.Saldivar: Ultrastructural Findings in the Murine Nonciliated Bronchiolar Cells (NCBC) after Subacute Inhalation of Lead Acetate. Acta Vet. Brno 1999, 68: 51-55. Air pollution is an important health problem in some countries. For Mexico City, repeatedly high levels of some metals including lead (Pb) have been reported. Since there is no relevant information, we used an inhalation model to identify the possible lung cell damage after exposure of animals to Pb. We used thirty CD-1 male mice that were inhaling (for 1 hour) aerosolized lead acetate 0.1M, three times per week during two weeks. Mice were sacrificed by cervical dislocation on days 1, 3, 5, 7, 10 and 15 after the last Pb exposure. Their lungs were fixed by intratracheal instillation of glutaraldehyde. Lung tissue for morphological observation and metal concentration was sampled. In the exposed mice, on days 3 and 5 changes in the nonciliated bronchiolar cells appeared. Whorl-like structures were present in the cell apex. These structures compressed other organelles. On day 5 after the final inhalation, the structures increased in size, and by day 10 they disappeared. After the last inhalation, the metal concentration in the lung tissue continuously decreased until day 7 when no more metal was detected. It was evident that the contact of the NCBC with Pb produces changes in the morphology of these cells. The metal concentrations in the lung decreased when the exposure ended. This finding supports the assumption that Pb is not accumulated in lung tissue. As a consequence, the cellular modifications decreased and began their way to morphological recovery. Nonciliated bronchiolar cell, Clara cell, Pb, inhalation toxicology, bronchiole Air pollution is a major problem worldwide, particularly in areas such as Mexico City that is considered the most polluted city in the world. In some industrial areas of this city, air concentrations of lead (Pb) ranged from 7.5 to 14.5μg/m3 (three months average) as reported by Alber t and Badi l lo (1992). A report from our laboratory showed increased concentrations of Pb and other metals in human autopsied lungs when comparing a thirty-year period of the records of people who lived in Mexico City during the 1950’s to those of the ones who lived in the same city but in the 1980’s (For toul 1996). Lead is a component of the 0.1 to 1 μm size particles present in the air that enters the lungs by inhalation. Thirty to 50 % of Pb concentration in this organ is absorbed into blood and from here it is distributed into the whole organism. In situations when the exposure to polluted air is high, the dose by this route could be a great risk resulting in lead intoxication (Tsa lev 1985). Only few reports on Pb toxicity for lung tissue are available, and they mostly focus only on modifications in the function of the alveolar macrophages ACTA VET. BRNO 1999, 68: 51–55 Address for correspondence: Teresa I. Fortoul, M. D. Departamento de Biologia Celulary Tisular Edif. A 3er piso Facultad de Medicina UNAM CP 04510, Mexico City, Mexico Phone: +525 623-2360 Fax: +525 623-2182 or 623-2399 E-mail: fortoul@servidor.unam.mx (Zel ikof f 1993). Changes in the function of the immune system with decreased antibacterial resistance have also been mentioned (Ehr l ich 1980). Almost all written information available is about the effects of this metal on the hematopoietic system, on the kidney or on the nervous system. Lack of information exists as to the effects of inhalation of this metal directly in the lungs and changes in the morphology of cells involved in the detoxification of xenobiotics. The nonciliated bronchiolar cells (NCBC) are located in the ultimate conducting tubes of the lung; they are rich in cytochrome P-450 monooxigenases and they are the target of a number of xenobiotics including furans, aromatic and halogenated aliphatic hydrocarbons, ozone and others (Kanekal 1990; Serabj i t -Singh 1979; Boyd 1977). This cell type could also be a natural target for inhaled lead. We therefore conducted experimental Pb aerosol exposures using a mouse model to examine the morphologic changes in the nonciliated bronchiolar cells. Materials and Methods Lead acetate in deionized water was tested at concentrations of 0.001M, 0.01M and 0.1M. Light microscopy of the lungs revealed no changes with the first two concentrations, and only slight changes were observed with 0.1M. With these results it was decided to start the experiments using 0.1M concentration, and a schedule at which the animals would survive. Mice were selected as a model animal for their evident NCBC (Plopper 1991), and to make sure that the suspected target cells would be produced in such quantity, that the modifications would be easily detected. For one hour three times a week for two weeks, thirty CD-1 male mice weighing 35 ± 5 g inhaled a solution 0.1M of lead acetate in deionized water. The mice were placed in a plastic chamber volume of 72.7 l to which an ultrasonic nebulizer (Ultra Neb 99, DeVilbis) was attached. The nebulizer was designed to produce droplets in a 0.5 to 5 μm range. A trap for the vapor was located on the opposite side with a solution of sodium bicarbonate to precipitate the remaining Pb. Eighteen mice of the same weight were used as controls, inhaling solely the vehicle with the same schedule. As a second control for acetate, sodium acetate 0.1M was also inhaled by a group of twelve mice. After each exposure, mice were placed in plastic cages, and they had free access to water and food (Purina Chow) in 12 hour day and light cycles. After the final inhalation, mice were sacrificed by cervical dislocation on day 1, 3, 5, 7, 10 and 15 according to the local standard legislation for observing animal welfare. Immediately after cervical dislocation, the trachea was exposed and the lungs were fixed by intratracheal instillation with 2.5% glutaraldehyde in 0.1M sodium cacodylate buffer, pH 7.4 (470 mmol) at total lung capacity (TLC). After lung expansion, the trachea was tied up and the cardiopulmonary block was removed from the chest cavity. The left lower lobe was ligated and processed for transmission electron microscopy (TEM) following the usual technique in order to identify the terminal bronchiole (Sabat ini 1964). Determinat ion of Pb in the t issue We quantified the metal using a modified technique (Fortoul 1996). Results were defined as μg/g per dry lung tissue (EPA 1994; Keith 1983). Determinat ion of Pb concentrat ion in the inhaled air A filter was positioned at the outlet of the nebulizer, used in the entire experiment, for sixty minutes at a flow rate of 10 l/min. The 400 ml solution used during the entire experiment was nebulized. The filter was removed from the outlet after ten minutes of exposure and then weighed. The treatment of the filter was the same as that of the tissue samples. Using the fluxes dynamic equation C=M/V in which C was the concentration of Pb in the filtered air expressed as μg/m3; M corresponded to the total lead mass on the filter, expressed as μg. The volume V in m3 was V = Q*t in which Q was the flow rate in l/ min and t the time exposure expressed in minutes. Lead concentration in the filter was 7180 μg . The Volume (10 l/ min * 60 min.) = 0.06 m3 . Concentration of Pb in the inhaled air was 11966.6 μg/m3.

32 citations


Journal Article
TL;DR: The results suggest that prolonged exposure to the heavy metal attenuated PKC activity at an important developmental time to potentially adversely affect normal hippocampal function.
Abstract: This study has examined the effect of chronic inorganic lead exposure on phospholipid-dependent protein kinase C (PKC) activity, and the distribution of its alpha (alpha), beta II (betaII), gamma (gamma), and zeta (zeta) isozymes in subcellular fractions of the developing rat hippocampus. Dams were exposed to either 0 or 1000 ppm lead acetate in their drinking water for one week and mated. Offspring were exposed to lead in utero, via lactation, and directly in the drinking water after weaning. The offspring were sacrificed at postnatal days 1 (P1), 8 (P8), 15 (P15), and 29 (P29). PKC activity was determined in the post-synaptosomal supernatant (PSS) and synaptosomal (P-2) membrane fractions by an in vitro assay using histone as the phosphate acceptor. The selected PKC isozymes were detected by immunoblotting techniques. In control animals, PKC activity (pmole/min/mg total protein) in both subcellular fractions substantially increased between P1 and P8. In chronically exposed rats exhibiting clinically relevant blood lead concentrations, this marked increase in PKC activity on P8 was significantly attenuated in both subcellular fractions. On this postnatal day, the amount of immunodetectable PKC gamma was significantly higher in the synaptosomal membrane fraction of lead-exposed rats. Other isozymes were unaffected. These results imply that in lead-exposed animals the PKC gamma isozyme was inactive even though it was associated with the membrane. These results also suggest that prolonged exposure to the heavy metal attenuated PKC activity at an important developmental time to potentially adversely affect normal hippocampal function.

Journal ArticleDOI
TL;DR: Data suggest that inhibition of cNOS activity and increase in iNOS may contribute to the Pb effects on the CNS, and the concentration of lead in blood, capillaries and synaptosomes in brain from mice receiving 0, 250, 500, and 1000 ppm of lead for 14 days through the drinking water.

Journal ArticleDOI
TL;DR: The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso‐DMSA might be the treatment of choice in acute lead poisoning in infants.
Abstract: The very young are more prone to lead poisoning than adults, and the treatment with chelating agents, either as monotherapy or combined treatment, is still a matter of dispute. The purpose of this work was to evaluate the efficiency of three chelating agents administered either as monotherapies or as combined treatments in sucklings. Lead acetate (5 mg Pb kg−1 i.p.) was administered to the 7-day-old rat pups in eight litters on experimental day 1 and chelating agents on experimental days 2 and 3. Pups were divided into six groups: (1) untreated control; (2) EDTA (calcium disodium ethylendiaminetetraacetate, 0.3 mmol kg−1 i.p. at 4 p.m.); (3) meso-DMSA (meso-2,3-dimeracaptosuccinic acid, 0.5 mmol kg−1 p.o. at 10 a.m.); (4) rac-DMSA (racemic-2,3-dimeracaptosuccinic acid, 0.5 mmol kg−1 p.o. at 10 a.m.); (5) EDTA+meso-DMSA; and (6) EDTA+rac-DMSA. Rats were killed on experimental day 5. Tissue element concentrations were analyzed by atomic absorption spectrometry. Treatment with EDTA did not affect tissue Pb, but it reduced Zn in the carcass and liver. Meso-DMSA reduced Pb in the kidneys and brain, and it did not affect organ essential elements. Rac-DMSA most efficiently reduced Pb concentrations in the carcass, kidneys and brain, but it also reduced Zn and Cu in the liver and Zn in the kidneys. Combined treatments with EDTA never improved the efficiency of either DMSA isoform in decreasing tissue Pb but they did reduce tissue Zn concentrations. All treatments caused the same decrease in the carcass Ca concentrations. The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso-DMSA might be the treatment of choice in acute lead poisoning in infants. Copyright © 1999 John Wiley & Sons, Ltd.

Journal ArticleDOI
TL;DR: Results indicate that male-mediated effects of lead may be observed in the 2-cell embryo, and the alteration observed in embryonic gene expression with paternal lead exposure may be useful for studying the role of the paternal contribution to the activation of the embryonic genome and protein synthesis in the early embryo.

Journal ArticleDOI
11 Aug 1999-JAMA
TL;DR: A direct physical measurement of 2 samples of Jackson's hair (1 from 1815, 1 from 1839) using cold vapor generation techniques, while lead levels were measured by electrothermal atomic absorption spectrophotometry as discussed by the authors.
Abstract: Historians have suggested that US president Andrew Jackson (1767-1845) experienced lead and mercury poisoning following his therapeutic use of calomel (mercurous chloride) and sugar of lead (lead acetate). To evaluate these claims, we performed direct physical measurement of 2 samples of Jackson's hair (1 from 1815, 1 from 1839). Following pretreatment and acid digestion, mercury was measured using cold vapor generation techniques, while lead levels were measured by electrothermal atomic absorption spectrophotometry. Mercury levels of 6.0 and 5.6 ppm were obtained from the 1815 and 1839 hair specimens, respectively. Lead levels were significantly elevated in both the 1815 sample (mean lead level, 130.5 ppm) and the 1839 sample (mean lead level, 44 ppm). These results suggest that Jackson had mercury and lead exposure, the latter compatible with symptomatic plumbism in the 1815 sample. However, Jackson's death was probably not due to heavy metal poisoning.

Journal ArticleDOI
TL;DR: Investigation of the kidney 2‐DE profile in lead‐exposed rabbit may be useful in understanding the mechanism of lead nephrotoxicity in humans, and a set of quantitatively altered charge variants was tentatively identified as glutathione‐S‐transferase (GST), based on similar observations in rodents subjected to short‐term, very high lead exposure.
Abstract: It was recently reported that low blood lead levels impaired kidney function in men To develop a set of molecular markers of renal lead exposure and effect, we investigated changes in renal protein expression while approximating occupational lead exposure at subchronic, low blood levels Lead was administered to male Dutch Belted rabbits as a lead acetate solution adjusted weekly to achieve and maintain the target blood lead levels of 0, 20, 40, and 80 microg/dL for 15 weeks Lead exposure did not affect kidney or body weights The effect of increasing blood lead on protein expression was evaluated in rabbit kidney by large-scale two-dimensional electrophoresis (2-DE) Significant quantitative changes (p < 005) occurred in a dose-related manner in 12 proteins at 20 microg/dL exposure, 25 at 40 microg/dL, and 102 at 80 microg/dL At a higher level of significance (p < 0001), 40 microg/dL blood lead resulted in one protein alteration and 80 microg/dL affected 14 proteins A set of quantitatively altered charge variants was tentatively identified as glutathione-S-transferase (GST), based on similar observations in rodents subjected to short-term, very high lead exposure The significance of the protein alterations observed as markers of toxicity awaits their conclusive identification Investigation of the kidney 2-DE profile in lead-exposed rabbit may be useful in understanding the mechanism of lead nephrotoxicity in humans

Journal ArticleDOI
TL;DR: In this paper, the effect of lead acetate on nephrotoxicity and its correlation with the nitric oxide (NO) system by determining the NAG release in perfused rat kidney was investigated.

Journal ArticleDOI
TL;DR: The thyroidal biological half-life of 131I (Tbiol) was found to have clearly increased following the lead/lithium treatment, thus reflecting an increased retention of 131B, and a progressive decline of the circulating T3 and T4 levels following lead or lithium treatment was noticed.
Abstract: The influence of lead acetate (50 mg per kg body weight) on the 131iodine (131I) biokinetics (uptake and retention) in rat thyroid and serum levels of triiodothyronine (T3) as well as thyroxine (T4) was evaluated as a function of time and in combination with lithium treatment. The 2-h and 24-h uptake of 131I in the thyroid was stimulated significantly by lead treatment. The 24-h uptake showed a maximum stimulation after 4 months of lead treatment. Lithium supplementation, however, showed the opposite effect by reducing the iodine uptake, whereby the maximum decrease was noticed after 2 months of treatment. Further, simultaneous lead and lithium treatment resulted in an even more pronounced increase of 2-h 131I uptake with a maximum after 3 months. However, the 24-h uptake after 3 months and 4 months of treatment did not differ significantly from the lead treated reference groups. The thyroidal biological half-life of 131I (Tbiol) was found to have clearly increased following the lead/lithium treatment. Interestingly, the combined lead/lithium treatment applied for 4 months caused a further growth of Tbiol, thus reflecting an increased retention of 131I. A maximum increase of Tbiol was seen after 2 months of combined treatment. A progressive decline of the circulating T3 and T4 levels following lead or lithium treatment was noticed and was more pronounced after combined treatment.

Journal ArticleDOI
TL;DR: Weight loss, especially rapid weight loss, could result in lead toxicity in people with a history of prior excessive lead exposure, and there were no significant differences in blood and organ lead concentrations between the swimming and nonswimming groups.
Abstract: We studied the effects of weight loss and non-weight-bearing exercise (swimming) on blood and organ lead and essential metal concentrations in rats with prior lead exposure. Nine-week-old female Sprague-Dawley rats (n = 37) received lead acetate in their drinking water for 2 weeks, followed by a 4-day latency period without lead exposure. Rats were then randomly assigned to one of six treatment groups: weight maintenance with ad libitum feeding, moderate weight loss with 20% food restriction, and substantial weight loss with 40% food restriction, either with or without swimming. Blood lead concentrations were measured weekly. The rats were euthanized after a 4-week period of food restriction, and the brain, liver, kidneys, quadriceps muscle, lumbar spinal column bones, and femur were harvested for analysis for lead, calcium, copper, iron, magnesium, and zinc using atomic absorption spectrophotometry. Both swimming and nonswimming rats fed restricted diets had consistently higher blood lead concentrations than the ad libitum controls. Rats in the substantial weight loss group had higher organ lead concentrations than rats in the weight maintenance group. Rats in the moderate weight loss group had intermediate values. There were no significant differences in blood and organ lead concentrations between the swimming and nonswimming groups. Organ iron concentrations increased with weight loss, but those of the other metals studied did not. Weight loss also increased hematocrits and decreased bone density of the nonswimming rats. The response of lead stores to weight loss was similar to that of iron stores because both were conserved during food restriction in contrast to decreased stores of the other metals studied. It is possible that weight loss, especially rapid weight loss, could result in lead toxicity in people with a history of prior excessive lead exposure.

Journal ArticleDOI
TL;DR: The results suggest that lead acetate is genotoxic at relatively high doses and repeated dose treatment show higher percentage of chromosomal aberrations than single dose treatment.
Abstract: The genotoxic effect of lead acetate in male mice was investigated as measured by sister chromatid exchange (SCE), chromosomal aberration analysis in both somatic (bone-marrow) and germ cells (spermatocytes) and the sperm morphology assay. Intraperitoneal treatment with the lowest tested dose (25 mg kg-1 b.wt.) had no genotoxic effects at all points of treatment and its effect was the same as the control (non-treated). Lead acetate was found to be potent inducer of SCE's at the doses 50 and 100 mg kg-1 b.wt. where the mean frequency of SCE's reached 12.09 ±0.62/cell compared with 12.52±0.52 for mitomycin C (positive control). Lead acetate at the doses 50, 100, 200, 400 mg kg-1 b.wt. (single i.p.) increased the percentage of chromosomal aberrations significantly in mice bone-marrow as well as in mice spermatocytes. The intensity of the effect is a function of lead concentration. Moreover repeated dose treatment show higher percentage of chromosomal aberrations than single dose treatment. Morphological sperm head abnormalities increased significantly after treatment with the doses 50 and 100 mg kg-1 b.wt. with a dose dependent relationship indicating a specific genotoxic effect of lead acetate on testis with the higher dose (100 mg kg-1 b.wt.).In conclusion the results suggest that lead acetate is genotoxic at relatively high doses.

Journal ArticleDOI
TL;DR: The data indicate that lead may exert its effect on the forced swimming test by directly or indirectly inhibiting the NMDA receptor complex.
Abstract: It has been reported that lead can cause behavioral impairment by inhibiting the N-methyl-D-aspartate (NMDA) receptor complex. MK-801, a noncompetitive NMDA receptor antagonist, exhibits an antidepressant-like action in the forced swimming test. The purpose of the present study was to determine whether subacute lead exposure in adult male Swiss mice weighing 30-35 g causes an antidepressant-like action in a forced swimming test. Mice were injected intraperitoneally (ip) with 10 mg/kg lead acetate or saline daily for 7 consecutive days. Twenty-four hours after the last treatment, the saline and lead-treated mice received an injection of MK-801 (0.01 mg/kg, ip) or saline and were tested in forced swimming and in open-field tests. Immobility time was similarly reduced in the saline-MK-801, Pb-saline and Pb-MK-801 groups compared to the saline-saline group (mean +/- SEM; 197.3 +/- 18.5, 193.5 +/- 15.8, 191.3 +/- 12.3 and 264.0 +/- 14.4 s, respectively; N = 9). These data indicate that lead may exert its effect on the forced swimming test by directly or indirectly inhibiting the NMDA receptor complex. Lead treatment caused no deficit in memory of habituation and did not affect locomotor activity in an open-field (N = 14). However, mice that received MK-801 after lead exhibited a deficit in habituation (22% reduction in rearing responses between session 3 and 1; N = 14) as compared to control (41% reduction in rearing responses; N = 15), further suggesting that lead may have affected the NMDA receptor activity. Forced-swim immobility in a basin in two daily consecutive sessions was also significantly decreased by lead exposure (mean +/- SEM; day 1 = 10.6 +/- 3.2, day 2 = 19.6 +/- 3.6; N = 16) as compared to control (day 1 = 18.4 +/- 3.8, day 2 = 34.0 +/- 3.7; N = 17), whereas the number of crossings was not affected by lead treatment, further indicating a specific antidepressant-like action of lead.

Journal ArticleDOI
TL;DR: Structural changes of rat submandibular glands after long-term treatment with various doses of lead showed that lead treatment resulted in accumulation of lead in rats'SMGs, and lead treatment also caused degenerative changes in the cells.
Abstract: Structural changes of rat submandibular glands (SMG) after long-term treatment with various doses of lead (0.01%, 0.04%, 0.05%) were investigated in this study. After termination of treatment, SMGs were removed and homogenized for measurement of total protein, DNA, calcium, and lead concentrations. Also ultrastructural examination of glands by electron microscopy was carried out. Total protein, DNA, and intracellular calcium concentrations of treated glands at 0.04% and 0.05% lead concentrations showed significant reduction when compared with those of controls. Data of lead measurement, as determined by atomic absorption spectroscopy, showed that lead treatment resulted in accumulation of lead in rats'SMGs. Lead treatment also caused degenerative changes in the cells. Dilation of rough endoplasmic reticulum (RER) and swollen mitochondria were observed in the (0.05%) treated group. Transformation and enlargement of mitochondria also were determined in the (0.04%) treated group. We propose that lead treatme...


Journal ArticleDOI
TL;DR: It is suggested that the findings, which support earlier observations that raccoons are fairly resistant to lead, may be of value in studying interactions between lead exposure and oral vaccination of wildlife against rabies.

Journal ArticleDOI
TL;DR: It was demonstrated that exocrine cell mitochondria are particularly predisposed to lead effect, and intoxication of rats with lower lead doses causes reversible adaptative or compensatory changes in these organelles, which induces irreversible ultrastructural alterations in numerous mitochondria.

Journal ArticleDOI
TL;DR: Rats receiving ethanol and lead simultaneously demonstrated abnormalities in heme biosynthesis similar to those in rats exposed to lead, although zinc hepatic levels decreased significantly only in animals exposed to both xenobiotics.

Journal ArticleDOI
TL;DR: The addition of lead acetate and of other metal salts appears to have an inhibitory effect on L-tryptophan binding to hepatic nuclei.
Abstract: This study evaluated whether lead acetate or other selected metal salts would influence the binding of L-tryptophan to rat hepatic nuclei. Lead salts and other salts of cadmium, zinc, mercury, and molybdenum, when added alone, had only small effects on 3H-tryptophan binding to hepatic nuclei in vitro. However, each of these salts, when added along with unlabeled L-tryptophan (excess, 10(-4) M), caused significantly less inhibition of 3H-tryptophan binding to hepatic nuclei than did unlabeled L-tryptophan alone. Lead acetate (10(-10) to 10(-4) M), when added along with unlabeled L-tryptophan, abrogated the inhibition of binding related to unlabeled L-tryptophan alone. Sodium arsenite (but not potassium arsenate) as well as sodium selenite (at 10(-4) M concentrations) inhibited to a moderate degree the in vitro 3H-tryptophan binding to hepatic nuclei, but addition of 10(-4) dithiothreitol, a protective agent for sulfhydryl groups, diminished this inhibition. Rats receiving a high dose of lead acetate before being tube-fed L-tryptophan displayed a decrease in hepatic protein synthesis compared with the stimulatory response connected with L-tryptophan alone. Thus, the addition of lead acetate and of other metal salts appears to have an inhibitory effect on L-tryptophan binding to hepatic nuclei. Lead acetate was investigated in in vivo experiments and was found to negate the stimulation of hepatic protein synthesis related to L-tryptophan alone.

Journal ArticleDOI
TL;DR: In this article, PbSe has been synthesized for the first time by γ-irradiation method from an ethylenediamine solution containing lead acetate and elemental selenium at room temperature and in ambient pressure.
Abstract: 30 nm PbSe has been synthesized for the first time by γ-irradiation method from an ethylenediamine solution containing lead acetate and elemental selenium at room temperature and in ambient pressure.

Journal Article
TL;DR: Dehydration apparently reveals an underlying neurotoxic action of lead at the neuromuscular junction and raises a health concern that people subjected to both lead pollution and dehydration are at greater risk to lead poisoning of the neuromechanical junction.
Abstract: The effect of 24 hrs. water deprivation on spontaneous and evoked transmitter release was studied at flexor nerve terminals of control and lead-treated male C57BL mice. Miniature endplate potentials (MEPPs) and endplate potentials (EPPs) were recorded intracellularly from urethane-anesthetized (2 mg/g, i.p.) control and lead exposed mice in both hydrated and dehydrated conditions. Exposure to lead was made by i.p. injection of lead acetate (1.0 mg/kg) dissolved in a 5% glucose solution 24 hrs. prior to the experiment. Unimodal and bimodal MEPP frequencies decreased with dehydration, while small mode MEPPs remained unchanged and large mode MEPPs increased in frequency. EPP amplitude and quantal content were unchanged by dehydration. Lead treatment by itself reduced the frequency of unimodal and bimodal MEPPs but had no effect on the amplitude of EPPs or of quantal content. However a combination of dehydration and acute lead treatment reduced the frequency of unimodal, bimodal and large mode MEPPs and significantly reduced both EPP amplitude and quantal content. Dehydration apparently reveals an underlying neurotoxic action of lead at the neuromuscular junction. This raises a health concern that people subjected to both lead pollution and dehydration are at greater risk to lead poisoning of the neuromuscular junction.