Showing papers on "Lead acetate published in 1993"

Comparison of lead bioavailability in F344 rats fed lead acetate, lead oxide, lead sulfide, or lead ore concentrate from Skagway, Alaska

Abstract: An animal model using rats was developed to initiate investigations on the bioavailability of different sources of environmental lead. Lead must be absorbed and transported to target organs like brain, liver, kidney, and bone, before susceptible cells can be harmed. The bioavailability and therefore the toxicity of lead are dependent upon the route of exposure, dose, chemical structure, solubility, particle size, matrix incorporation, and other physiological and physicochemical factors. In the present study male F344 rats were fed < or = 38 microns size particles of lead sulfide, lead oxide, lead acetate, and a lead ore concentrate from Skagway, Alaska, mixed into the diet at doses of 0, 10, 30, and 100 ppm as lead for 30 d. No mortality or overt symptoms of lead toxicity were observed during the course of the study. Maximum blood lead concentrations attained in the 100 ppm groups were approximately 80 micrograms/dl in rats fed lead acetate and lead oxide, and were approximately 10 micrograms/dl in those fed lead sulfide and lead ore concentrate. Maximum bone lead levels in rats fed soluble lead oxide and lead acetate were much higher (approximately 200 micrograms/g) than those seen in rats fed the less soluble lead sulfide and lead ore (approximately 10 micrograms); kidney lead concentrations were also about 10-fold greater in rats fed the more soluble compared to the less soluble lead compounds. However, strong correlations between dose and tissue lead concentrations were observed in rats fed each of the four different lead compounds. Kidney lesions graded as minimal occurred in 7/10 rats fed 30 ppm and in 10/10 rats fed 100 ppm lead acetate, but not at lower doses or from other lead compounds. Similarly, urinary aminolevulinic acid excretion, a biomarker for lead toxicity, was increased in rats fed 100 ppm lead acetate or lead oxide, but was unaffected at lower doses or by the less soluble lead compounds. Although the histological and biochemical responses to lead toxicity were restricted to the more soluble lead compounds in this study, lead from Skagway lead ore concentrate and lead sulfide was also bioavailable, and accumulated in proportion to dose in vulnerable target organs such as bone and kidney. Longer-term studies with different mining materials are being conducted to determine if tissue lead continues to increase, and whether the levels attained are toxic. Data from such studies can be used to compare the toxicity and bioavailability of lead from different sources in the environment.

Lipid abnormalities in rats given small doses of lead

Abstract: Previous human and experimental studies have demonstrated that lead exposure may modify the metabolism of lipids. Several studies have indicated that exposure to lead produces an increase in lipid peroxidation and inhibits blood superoxide dismutase activity. Recently, lipid peroxides have been shown to impair tissue membranes and to be a risk factor for vascular diseases. The aim of the present investigation was to evaluate the impact of subclinical lead poisoning on rat lipids in the context of atherosclerosis. The degree of poisoning was analogous to that in populations exposed to lead in a contaminated environment. Experiments were performed on male Buffalo rats with body weights of 150–200 g. The experimental animals received lead acetate intragastrically in doses of 35 mg lead/kg body wt. (Pb/kg) once weekly or 70 mg Pb/kg twice weekly for 7 weeks. Control rats were fed in the same manner with sodium acetate equimolar to the acetate in the lead acetate solution. One day after the feeding was over, venous blood samples, under ether anesthesia, were collected. The animals were killed by exsanguination and the liver was excised for determination of the metal (lead, copper, and zinc) content. A segment of the abdominal aorta was excised for histological examination. In venous blood the following were estimated: triglycerides, total cholesterol, high-density lipoprotein (HDL)-cholesterol fraction, serum lipid peroxides, and blood superoxide dismutase activity. Metal content (lead, copper, and zinc) in blood and liver was determined by means of atomic absorption spectrophotometry. In rats poisoned with small doses of lead, decreases in the plasma cholesterol level and the HDL-cholesterol fraction were observed. In parallel with the decrease in the cholesterol concentration, lead increases the serum triglyceride level, this increase being dependent upon lead levels in blood. In our studies a significant influence of lead on serum lipid peroxide level or blood superoxide dismutase activity was not found. In the histological examination, atrophy of the elastic fibers in the aorta was observed. The possible significance of the inhibitory effect of lead on lipoprotein lipase activity is discussed.

Effect of Ingestion and Inhalation of Lead on the Reproductive System and Fertility of Adult Male Rats and their Progeny

Abstract: Ninety-day-old Sprague-Dawley rats were intoxicated for 70 d with lead, given either as 0.3% lead acetate in drinking water or by inhalation as 5 mg m-3 lead oxide. Direct or transmitted lead toxicity for the male reproductive system was assessed in the rats and their offspring from pituitary and genital organ weights after exposure, the numbers of Sertoli and germ cells, the number, motility and morphology of epididymal spermatozoa, the levels of plasma testosterone, LH and FSH and fertility tests. Whole blood lead levels were similar after lead ingestion and after inhalation (58.0 ± 1.7 μg dl-1 vs. 51.1 ± 1.8 μg dl-1). Lead acetate ingestion did not affect the reproductive system or fertility of rats. Inhalation of lead oxide did not affect fertility either, but seminal vesicle weight dropped significantly, which might suggest an alteration in the pattern of testosterone secretion. In the male progeny of sires that inhaled lead, the number of epididymal spermatozoa decreased but this did not interfere w...

Effect of long-term exposure to lead on testis and epididymis in rats.

Abstract: The relation was studied between the morphology of tests and epididymides on the one hand, and the lead content in these organs on the other. The testes of rats, which for the time of 5 spermatogeneses (9 months) were drinking 1% lead acetate(II), displayed all generations and layers of spermatogenic cells at respective stages of the seminiferous epithelium cycle. The lead content in testes of the animals did not differ significantly from the value of this element in gonads of control rats. The epididymal cells also failed to show morphological changes however, in all epididymal zones there were fewer spermatozoa than in the corresponding zones in control rats. Many spermatozoa revealed abnormal reactions of oxidoreductive enzymes in the midpiece. There were also local defects in tetrazolium salt reduction and segmental or total lack of formazan deposits in the mitochondrial sheath. The lead content in epididymes of these animals was significantly higher than in epididymides of control rats. The obtained results of the studies highlight the possibility for lead to accumulate in epididymis, and for lead compounds to damage spermatozoa in this organ.

Experimental model of lead nephropathy. III. Continuous low-level lead administration.

Abstract: We sought to determine whether continuous low-level lead exposure (100 ppm lead acetate in drinking water) for periods of 1, 3, 6, 9, or 12 mo would produce adverse effects on kidney function or morphology in rats. Maximum blood lead levels in experimental animals were reached at 3 mo and averaged 29.4 ± 4.1 μg/dl. Glomerular filtration rate, determined by single-injection 125I-iothalamate clearance, was found to be significantly increased above pair-fed controls at 1 and 3 mo, but it was normal at other time periods. Levels of urinary N-acetyl-β-D-glucosaminidase exceeded levels found in controls at all time periods, except at 12 mo, when the normal increase with aging obscured differences between experimental animals and controls. In contrast, urinary ligandin (glutathione S transferase), a more specific marker of metal-associated proximal tubular injury, was normal at all time periods. Proximal tubular nuclear inclusion bodies were sparse and were observed only at 1 and 3 mo. There were no oth...

Mechanisms of the toxic effect of lead. I. Free lead in erythrocyte.

Abstract: In this work, a selection of children was examined based on their free erythrocyte protoporphyrin (FEP) and total blood lead (PbB) contents. Two groups with clear differences in lead sensibility were selected. One group with high FEP levels (deep lead alteration), named "normal," and one group with low FEP levels (discrete lead alteration), named "lead tolerant," and both with similar PbB concentration, were formed. The selection, based on FEP level, showed a correlation with other indicators (neuromotor alterations). A lower activity of the enzymes Glyceraldehyde 3-phosphate dehydrogenase (GA3PD), Glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and Lactate dehydrogenase (LDH) was found in the normal group when compared to the tolerant group. Therefore, the influence of the lead acetate upon the same erythrocyte enzyme activities was investigated. Lead inhibition of the enzymes GA3PD and G6PD was found, and this inhibition could be related to the free lead content found in the erythrocytes. Inhibition of the enzymes 6PGD and LDH was also found, but these enzymes were not inhibited by exposure to lead acetate. Erythrocyte free lead content was high in the normal group when compared to the lead tolerant group and could be a determinant factor in the biochemical alterations found. Low erythrocyte free lead contents could be an indicator of lead tolerance. TCA-precipitation was found to be a useful method to evaluate free lead content; it gave similar results to gel filtration molecular chromathography.

Effects of lead on glucose metabolism, ion flux, and collagen synthesis in cerebral capillaries of calves.

Abstract: Brain capillary function was assessed in 4- to 6-week-old calves given lead acetate (15 mg/kg of body weight) orally for 7 to 8 days. Neurologic signs of lead poisoning included CNS depression, blindness, and hyperesthesia. Brain capillaries were isolated from cerebral cortex of control and lead-treated calves and evaluated for metabolic indicators, ion transport, and prolyl hydroxylase activity. In lead-treated calves, the rate of glucose metabolism was less than half that in controls. Ion efflux of 45Ca or 36Cl from endothelial cell suspensions was not affected by lead treatment. Prolyl hydroxylase activity in endothelium and proline-to-hydroxyproline ratio in endothelial basement membranes were similar in control and lead-poisoned calves. Results indicate that lead may inhibit energy metabolism, but not ion transport or collagen biosynthesis in brain capillaries of calves and, compared with suckling rats, damage to the blood-brain barrier is less important. In calves, neuronal tissue may be the primary target for the CNS effects of lead.

Chronic lead exposure induces ultrastructural alterations in the monkey testis.

Abstract: The purpose of this study was to establish the effects of lead on the non-human primate testis. Sixteen cynomolgus monkeys maintained in environmentally controlled conditions were administered 1500 micrograms lead acetate/kg bw/day in gelatin capsules. Monkeys were randomly assigned to the following groups: control (n = 3), which received 95% glycerol and 5% distilled water (vehicle) over their lifetime for 9 years; infancy group (n = 4), exposure limited to the first 400 days of life; post-infancy group (n = 5), dosed following 300 days of life to 9 years of age; lifetime group (n = 4), dosed for nine years. All the animals were treated with lead or vehicle for the entire duration of the experiment. The organs from animals in the control group consisted of seminiferous epithelium comprised of typical Sertoli cells containing nuclei with numerous infoldings and longitudinally-oriented profiles of endoplasmic reticulum, microtubules, mitochondria, and lipid droplets that were scarce. Spermatogenic cell types at different developmental stages were observed. Seminiferous epithelium from animals of the treated groups exhibited distortion in the general architecture of the epithelium such that a marked decrease in its height was revealed. In particular, Sertoli cells contained heightened number of lipid droplets and lysosomal elements, and the basal lamina was usually stratified. The magnitude of alterations in the seminiferous tubules was indistinguishable among the three treated groups. These findings support the conclusion that lead is a potent testicular toxin.

Effect of experimental lead toxicity on cardiovascular function in calves.

Abstract: The effect of lead was studied on cardiovascular function in calves given oral doses of 5 mg lead acetate/kg body weight daily till the appearance of clinical signs of toxicity. Arterial blood pressure and electrocardiogram were recorded before (day 0) and on days 30 and 60 of lead administration. There was a significant increase in arterial blood pressure in lead-intoxicated calves on day 30 (124.8 +/- 1.0 mm Hg) with the peak values noted on day 60 (150.8 +/- 4.3 mm Hg). ECG in lead 11 showed marked increases in P wave duration and amplitude and duration of P-R interval. Duration of Q-T interval was decreased and T wave was inverted after 30 days of continuous lead exposure. Histopathological examination showed degeneration of cardiac musculature, mononuclear cell infiltration and swelling of Purkinjee fibers in calves sacrificed after the onset of irreversible signs of lead toxicity.

Effect of acute pretreatment of lead on picrotoxin-induced convulsions in rats.

Abstract: The effect of acute exposure to lead acetate (LA)/lead nitrate (LN) on onset and severity of convulsions induced by a low dose of picrotoxin was examined in rats. Both LA and LN reduced the time of onset and exacerbated the severity of convulsions, with a resultant high lethality. On comparison, it was noted that in the LA-pretreated group, convulsion scores and incidence of tonus and mortality were much higher; the appearance of tonus was more delayed than in the LN-pretreated group. In lead-pretreated animals, the potentiation of picrotoxin-induced convulsions was accompanied by higher lead levels in blood (p < 0.001). However, the whole-brain lead levels were not significantly different in these animals compared to the controls. The difference in the degree of potentiation by the two forms of lead could possibly be attributed either to the role of a combination of anions and cations or to the variable cerebral uptake and regional distribution of lead or due partly to the extent of competitive interaction involving d-aminolaevulinic acid--whose level is known to be elevated consequent to lead-induced disruption of haem biosynthesis--at GABA receptors.

Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver.

Abstract: The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.

Chronic lead exposure induces ultrastructural alterations in the monkey seminal vesicle.

Abstract: Lead is a toxic and carcinogenic metal that has been extensively associated with male reproductive abnormalities. The purpose of this study was to establish the effects of lead on the primate seminal vesicle. Sixteen cynomolgus monkeys maintained in environmentally controlled conditions were orally administered gelatin capsules containing 1500 micrograms lead acetate/kg bw/day. Monkeys were randomly assigned to the following groups: control (n = 3) which received 95% glycerol and 5% distilled water (vehicle) over their lifetime, infancy (limited to the first 400 days of life; n = 4), post-infancy (dosed following 300 days of life to 9 years of age; n = 5) and lifetime exposure (9 years; n = 4). At necropsy, the seminal vesicles from each animal were removed, fixed in glutaraldehyde, and processed for ultrastructural analysis by conventional methods. The glands from animals in the control group consisted of acini lined by two cell types, viz., tall columnar secretory cells, and round basal cells. Secretory cells possessed microvilli, basally located nuclei surrounded by much rough endoplasmic reticulum, a few lipid droplets, and supra-nuclear regions dominated by pleomorphic membrane-limited secretory granules. All the treated groups exhibited an augmentation in the number of lipid droplets within the secretory cells. In both the infancy and post-infancy groups, a marked reduction in electron-dense cores of the secretory droplets was observed in severely affected regions of the glands. These findings support the evidence that lead is a potent reproductive toxicant, however, further research is needed to determine the consequences of this damage on reproductive performance.

Effect of additives on the anodic codeposition of lead dioxide and polypyrrole

Abstract: The influence of acetate, Pb2+ species and pyrrole on the electrodeposition of lead dioxide and polypyrrole on a glassy carbon electrode in 1.0m potassium nitrate medium was studied using cyclic voltammetry, double potential step chronoamperometry and controlled potential electrolysis techniques. In the presence of acetate ion the deposition of lead dioxide initiates at least 200 mV less positive compared to nitrate ions alone. At lower acetate ion concentration ( 20 mm) acetate ions are found to inhibit polypyrrole formation. The following is the decreasing order of inhibition of polypyrrole formation. Sodium acetate > lead nitrate > lead acetate. Acetate in the form of lead acetate is found to favour simultaneous deposition of lead dioxide and polypyrrole with minimum inhibition on polypyrrole formation.

[Lead: histopathological findings in experimental contamination].

Abstract: The aim of the present paper is to show lead toxicity and cell deposition of concentrations lower than those regarded as toxic on an experimental model with rats C3Hs., forty five grams-rats were used. A standard diet was administered together with water ad-libitium, containing very low doses of lead acetate which was constantly administered and at fixed periods. Light and electron microscopy were used to study the liver and the spleen. These organs are considered to harbour a great amount of constant macrophages with phagocytic function. The findings showed lesions and lead deposits which confirmed the causative agent as well as its toxic contaminating action.

Effect of lead acetate and carbon particles on the expression of glutathione S-transferase YfYf in rat liver

Abstract: Administration of intracardiac lead acetate produces a complex response in glutathione S-transferase (GST) YfYf expression in rat liver. The earliest response, an elevation of GST expression in Kupffer cells, can be mimicked by administering a suspension of carbon particles. The second effect of lead acetate administration is a marked elevation of GST YfYf in some but not all hepatocytes (the 'patchy' response). This effect is most marked 48-76 h after administration of a single dose of lead acetate and is easily detected by immunoblotting. Dexamethasone down-regulates the lead response in hepatocytes.

Effects of fasting on distribution and excretion of lead following long-term lead exposure in rats.

Abstract: Lead was given to rats through drinking water containing 100 ppm lead acetate for 20 days. Delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes was significantly lower (p < 0.05) at 20 days after Pb treatment. Erythrocytic ALAD activity was significantly lower (p < 0.05) in fasted rats than in fed rats with or without Pb pretreatment. Serum glutamic pyruvic transaminase and glutamic oxaloacetic transaminase activities after 6 days of fasting were significantly higher (p < 0.05) in Pb pretreated rats than in other groups (Ph nontreated fed and fasted rats, and Pb pretreated fed rats). Long periods of fasting strongly enhanced these serum-enzymes elevations induced by lead. Maximum Pb concentrations and total amount in feces increased in rats fasted for 3 days regardless of Pb pretreatment. On the other hand, total amount of Pb in feces of rats fasted for 6 days were not significantly different from the other groups because their fecal volume decreased to about 1 % of fed rats. The Pb concentrations of liver, kidney, spleen, and femur increased significantly in Pb pretreated rats compared to in controls, but there were no significant differences between the fed and fasted rats.

Influence of lead acetate on the histological, ultrastructural and histochemical picture of the livers of albino rats.

Abstract: The amount of lead pollution in the environment is increasing proportionally to the development of industry. Lead is capable of damaging the organism in many ways due to its high affinity to various tissues, different enzymes and serum proteins and its tendency to cumulate (1, 14). Acute lead poisoning occurs in people who have had intense, but short-term contact with organic lead compounds (tetraethylolead) used as an antidetonant in motor fuels, or plumbous orthoplumbate (red lead), which is an important component in anticorrosive paints (4, 6). Chronic poisoning by lead and lead salts, which used to occur in printers and workers in battery factories, is now a threat to the whole human population because of the hundreds of thousands of tons of tetraethylolead used as a fuel additive. This substance pollutes not only the atmosphere, but also the soil and the water and because of this, the food (10). The toxic effects of lead on the central and peripheral nervous system and the hematopoetic system is well known (9, 12), Less clear, however, are the toxic effects of this metal on the liver. As of now, there are still different views on the existence of negative effects of lead on the livers of people and animals exposed to this metal. Some researchers found no changes in the liver in cases of long-term contact with lead (3).

[Morphofunctional characteristics of the ovaries, thyroid gland and adrenal glands in experimental lead acetate poisoning].

Abstract: Daily doses of 50 mg/kg of lead acetate injected into the laboratory animals induce morphologic changes in the parenchyma of ovaries, thyroid gland, adrenals and compromises neural mediating processes in paraventricular and supraoptic nuclei of hypothalamus. The observed morphologic changes are similar to those characteristic for intensive functioning. Prolonged exposure to lead acetate (daily dose 10 mg/kg) results in adaptation and compensation, which preserves the functional potential of the organs. The morphologic changes in the endocrine organs do not lead to significant hormonal changes.

Effect of lead on anorexia and body weight in albino rats.

Abstract: Rats exposed to lead (lead acetate) in doses of 0.2 and 0.5 mg/ml in drinking water for a period of 90 days showed mild to moderate changes in food consumption compared to control group. Drug interactions in lead exposed rats with metoclopramide, atropine sulphate, propranolol, cyproheptadine and mepyramine maleate when administered intraperitoneally caused -30 to +30 percentage variation in food intake indicating the influence of adrenergic, serotonergic and cholinergic neurotransmitters with no change in mean body weight of lead treated rats.

Effect of Lead on Globin mRNA In Vivo and In Vitro

Abstract: Plumbous ion has been shown to be a potent catalyst for the depolymerization of RNA in vitro but the question of whether or not Lead-catalyzed RNA degradation also occurs in vivo has never been addressed. Our experimental design, to answer this question, was to transfuse rabbit reticulocytes into normal rabbits and rabbits that had been injected with different doses of lead acetate. After 24 hours the mRNA was isolated form the reticulocytes of each rabbit by phenol extraction and affinity chromatography on oligo dT cellulose. The amount of mRNA per ml of packed reticulocytes was determined. The integrity of the mRNA was then determined with a cell-free reticulocyte translation system that was dependent on exogenous mRNA. The results showed that there was little difference in the amount of mRNA recovered from control and treated rabbits, but the ability of the mRNA to support globin synthesis was decreased by as much as 86% in the lead-treated rabbits. These data suggest that not only is mRNA attacked by lead in vivo but that the lead attacks the mRNA at just one or at least very few sites. In the in vivo studies, purified rabbit globin mRNA was incubated with lead acetate andmore » the products of this reaction were labelled with {sup 32}P using T4 polynucleotide kinase. A labelled fragment of slightly greater mobility than tRNA was isolated by gel electrophoresis. This fragment was digested to the monomers and analyzed by TLC to identify the nucleotide at the 5' end.« less