Showing papers on "Lead acetate published in 2000"

Effects of lead on birds (Laridae): a review of laboratory and field studies.

Abstract: Lead is one of the most common metals in contaminated ecosystems. Although lead poisoning and mortality have long been known, little is known of the behavioral effects produced by low levels of lead in wild animals. Herein a 15-yr research program on the behavioral effects of lead using herring gulls (Larus argentatus) and common terns (Sterna hirundo), referred to as larids, as models is reviewed. The doses used in laboratory studies were sufficient to produce lead concentrations in feathers that were equivalent to those found in some birds living in the wild. The exposure consisted of a single or multiple intraperitoneal (ip) injection of lead acetate. Both dose and day of exposure influenced behavioral development in young larids, with most effects increasing with dose, and decreasing with age. Low-level lead affected growth, locomotion, balance, food begging, feeding, thermoregulation, depth perception, and individual recognition in laboratory and in wild birds. The accuracy of individual recognition ...

A role for oxidative stress in suppressing serum immunoglobulin levels in lead-exposed Fisher 344 rats.

Abstract: Evidence implicating oxidative stress in toxicity during lead intoxication in vivo has opened new avenues for investigation of the mechanisms of lead-induced immunosuppression. The current study explores the possibility that lead-induced oxidative stress contributes to the immunosuppression observed during lead poisoning. Fisher 344 rats were exposed to 2,000 ppm lead acetate in their drinking water for 5 weeks. One week following removal of lead from the drinking water, significant reductions in serum levels of IgA, IgM, and IgG were detected. Significant increases in oxidative damage, based on malondialdehyde (MDA) content, were observed in peripheral blood mononuclear cells (PMCs) collected during the same experiments. In addition, MDA content increased in livers from lead-exposed rats. Following 5 weeks of lead exposure, administration of either 5.5 mmol/kg N-acetylcysteine (NAC) or 1 mmol/kg meso-2,3-dimercaptosuccinic acid (DMSA) in the drinking water for 1 week significantly reversed the inhibitory effects of lead on serum immunoglobulin (Ig) levels. Also, all parameters indicative of oxidative stress returned to control levels. These results suggest that oxidative stress contributes to suppressed serum Ig levels during lead intoxication in vivo, and that intervention with either a thiol antioxidant (NAC) or a metal chelator (DMSA) will alleviate this lead-induced suppression by correcting the prooxidant/antioxidant imbalance caused by lead exposure.

Prophylactic effect of melatonin on lead-induced inhibition of heme biosynthesis and deterioration of antioxidant systems in male rats.

Abstract: We studied the protective role of the pineal hormone melatonin on lead-induced suppression of the heme synthesis pathway as a consequence of reduced antioxidant systems in rat. We injected rats intramuscularly with lead acetate (10 mg/kg body weight) daily for 7 days, which significantly abolished heme synthesis as evidenced by decreased blood hemoglobin, liver δ-aminolevulinic acid synthetase, erythrocytic δ-aminolevulinic acid dehydratase, and hepatic iron content. These effects were accompanied with marked elevation of hepatic lipid peroxidation and decreased enzymatic antioxidants such as glutathione reductase, glutathione-S-transferase, superoxide dismutase, and catalase, as well as nonenzymatic antioxidants such as total sulfhydryl groups and glutathione. Furthermore, lead treatment caused hepatic deficiency in copper and zinc accompanied by a significant elevation of lead concentration in both plasma and liver. Daily pretreatment with melatonin (30 mg/kg body weight) intragastrically prevented the suppressive effects of lead on heme-synthesizing enzymes and iron deficiency. In addition, preadministration of melatonin reduced the inhibitory effect of lead on both enzymatic and nonenzymatic antioxidants. This was accompanied by marked normalization of lipid peroxidation and modulation of copper and zinc levels in liver. The action of melatonin on lead-induced changes was attributed to protection of the antioxidant capacity in cells in addition to the ability of melatonin to scavenge free radicals. © 1999 John Wiley & Sons, Inc. J Biochem Toxicol 14: 57–62, 2000

Gender differences in developmental immunotoxicity to lead in the chicken : Analysis following a single early low-level exposure in ovo

Abstract: Lead has been shown previously to induce immunotoxic effects on macrophage and T-cell-associated functions after full-gestational exposure. To gain a better understanding of a single developmental exposure and the potential role of gender in immunotoxic responses to low levels of lead, 5-d-old avian embryos were injected once with lead acetate (5 or 10 microg). As juveniles (4 wk of age), animals were immunized with a foreign antigen, bovine serum albumin (BSA). At 6 and 8 wk, animals were sensitized with a self antigen, thyroglobulin (Tg). Immune parameters were examined at 6 and 10 wk of age. In males, anti-BSA immunoglobulin G (IgG) levels were significantly increased at the highest lead treatment level compared to sodium acetate controls, while female antibody production was unaltered. Similarly, after early exposure to lead, males (which were noninducible for anti-thyroglobulin antibodies in sodium acetate controls) were induced to produce autoanti-thyroglobulin IgG. Lead exposure did not markedly alter autoantibody levels in females, although, unlike males, control females could be induced to produce autoantibody to thyroglobulin. Males differed significantly in total leukocyte counts between treatment groups, whereas females did not. No marked differences were observed in males or females in the delayed-type hypersensitivity response, lymphocytic infiltration of thyroids, or in spleen, thymus, or bursa weights following exposure to lead. These results suggest that there is a differential immunotoxic effect based on gender after a single in ovo exposure to lead. Therefore, when examining the developmental immunotoxic effects of a metal such as lead, gender is a potential risk factor.

Developmental toxicity of lead-contaminated sediment to mallard ducklings

Abstract: Sediment ingestion has been identified as an important exposure route for toxicants in waterfowl. The toxicity of lead-contaminated sediment from the Coeur d'Alene River Basin (CDARB) in Idaho was examined on posthatching development of mallard (Anas platyrhynchos) ducklings for 6 weeks. Day-old ducklings received either untreated control diet, clean sediment (24%) supplemented control diet, CDARB sediment (3,449 μg/g lead) supplemented diets at 12% or 24%, or a positive control diet containing lead acetate equivalent to that found in 24% CDARB. The 12% CDARB diet resulted in a geometric mean blood lead concentration of 1.41 ppm (WW) with over 90% depression of red blood cell ALAD activity and over threefold elevation of free erythrocyte protoporphyrin concentration. The 24% CDARB diet resulted in blood lead of 2.56 ppm with over sixfold elevation of protoporphyrin and lower brain weight. In this group the liver lead concentration was 7.92 ppm (WW), and there was a 40% increase in hepatic reduced glutathione concentration. The kidney lead concentration in this group was 7.97 ppm, and acid-fast inclusion bodies were present in the kidneys of four of nine ducklings. The lead acetate positive control group was more adversely affected in most respects than the 24% CDARB group. With a less optimal diet (mixture of two thirds corn and one third standard diet), CDARB sediment was more toxic; blood lead levels were higher, body growth and liver biochemistry (TBARS) were more affected, and prevalence of acid-fast inclusion bodies increased. Lead from CDARB sediment accumulated more readily in duckling blood and liver than reported in goslings, but at given concentrations was generally less toxic to ducklings. Many of these effects are similar to ones reported in wild mallards and geese within the CDARB.

Lead Acetate Potentiates Brain Catalase Activity and Enhances Ethanol-Induced Locomotion in Mice

Abstract: Several reports have demonstrated that acute lead acetate administration enhances brain catalase activity in animals. Other reports have shown a role of brain catalase in ethanol-induced behaviors. In the present study we investigated the effect of acute lead acetate on brain catalase activity and on ethanol-induced locomotion, as well as whether mice treated with different doses of lead acetate, and therefore, with enhanced brain catalase activity, exhibit an increased ethanol-induced locomotor activity. Lead acetate or saline was injected IP in Swiss mice at doses of 50, 100, 150, or 200 mg/kg. At 7 days following this treatment, ethanol (0.0, 1.5, 2.0, 2.5, or 3.0 g/kg) was injected IP, and the animals were placed in the open-field chambers. Results indicated that the locomotor activity induced by ethanol was significantly increased in the groups treated with lead acetate. Maximum ethanol-induced locomotor activity increase was found in animals treated with 100 mg/kg of lead acetate and 2.5 g/kg of ethanol. Total brain catalase activity in lead-pretreated animals also showed a significant induction, which was maximum at 100 mg/kg of lead acetate treatment. No differences in blood ethanol levels were observed among treatment groups. 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 brain catalase in ethanol-induced behaviors.

Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenase of rat brain in vitro: relevance to sporadic Alzheimer's disease?

Abstract: Lead is known to be a potent inhibitor of many enzymes working in the brain, thus possibly inducing functional problems in the brain under pathophysiological conditions. Among such enzymes are those involved in glucose metabolism and energy production. We investigated the inhibitory effects of low-level lead on brain hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK) and pyruvate dehydrogenase complex (PDHc) with rat brain homogenate. PDHc was distinctively inhibited when low-dose lead acetate was added last of all (IC50 = 5 μM) to the reaction mixture. The other enzymes were completely resistant to 5 μM of lead acetate. When the homogenate was preincubated with lead acetate HK was dramatically inhibited by low-level lead acetate (1–5 μM), in a manner dependent on both preincubation time and lead concentration. However, the inhibitory effect was abolished by coincubation with its substrates, glucose or ATP. The results suggest that exposure to low levels of lead may increase the risk of cerebral hypometabolism caused by direct inhibition of specific glucose-utilizing enzymes. In this context, lead might be regarded as a risk factor in the abnormal glucose metabolism seen in some kinds of neurodegenerative disorders such as sporadic Alzheimer's disease.

L-arginine/nitric oxide pathway and interaction with lead acetate on rat submandibular gland function.

Abstract: : The effects of lead acetate, L-arginine (nitric oxide precursor) and L-NAME (nitric oxide synthesis inhibitor) on rat submandibular secretory function were studied. Pure submandibular saliva was collected intraorally from anaesthetized rats by a micro polyethylene cannula using pilocarpine as secretagogue. Treatment for twenty-eight days with three doses of lead acetate (0.01%, 0.04%, 0.05% w/v) in drinking water caused significant alterations on salivary function. Salivary flow rate was decreased by lead at all doses used. The total protein concentration and amylase activity of saliva were both decreased by lead (0.04% and 0.05%). All doses of lead decreased saliva calcium concentrations. Two weeks' treatment of rats by L-arginine (2.25% w/v) and L-NAME (0.7% w/v) in drinking water also affected the saliva secretory function. L-Arginine caused increase in submandibular gland weight. The saliva flow rate was reduced by L-NAME. The total protein concentration of saliva was increased by L-arginine and decreased by L-NAME. Amylase activity was reduced by L-arginine treatment. Calcium concentration was reduced by L-arginine and increased by L-NAME. Concurrent L-arginine treatment with lead acetate recovered lead-induced reduction of flow rate but L-NAME potentiated it. Concurrent therapy of lead and L-NAME resulted in greater reduction of protein concentration when compared to that of lead. L-Arginine showed a preventive effect on lead-induced decrease of protein concentration. Both L-arginine and L-NAME prevented lead-induced reduction in calcium concentration. It is concluded that nitric oxide plays a role in salivary gland function. Also lead acetate inhibitory effect on submandibular function is somewhat diminished by L-arginine and partially increased by L-NAME. It seems that lead acetate interacts with nitric oxide modulatory role in salivary gland.

Lead enhances NGF-induced neurite outgrowth in PC12 cells by potentiating ERK/MAPK activation.

Abstract: Although the neurotoxicity of lead exposure is well documented, the cellular and molecular mechanisms underlying lead neurotoxicity have not been well defined. We have investigated the effect of lead on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells and the role in this process of extracellular signal regulated protein kinase (ERK), a key component of NGF-induced differentiation. We found that exposure of cells to lead acetate (0.1 - 100μM) resulted in enhanced NGF-induced neurite outgrowth. Lead exposure also promoted formation of multiple neurites per cell in NGF-treated cells. However, lead alone did not cause neurite outgrowth. Lead also enhanced NGF-induced ERK phosphorylation and activation, but lead alone did not stimulate ERK. The MAP kinase kinase (MEK) inhibitor, PD98059, significantly decreased the effect of lead on NGF-induced neurite outgrowth and ERK activation. These findings indicate that exposure of cells to low, toxic levels of lead amplifies growth factor-induced neurite outgrowth by means of an ERK-dependent signaling pathway.

Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats.

Abstract: The effects of adult and perinatal lead treatment on the development of locomotor sensitization produced with repeated morphine administration was investigated. In Experiment 1, adult male rats received a diet containing 250 ppm lead acetate or a control diet for 43 days. Animals then received 10 mg/kg morphine sulfate or water vehicle (ip) and locomotor activity was monitored for 14 consecutive days. While both control and lead-exposed animals demonstrated a locomotor sensitization to morphine, the magnitude of the increased locomotor response was reduced in lead-treated animals. Subsequent analysis of blood-lead in the adult lead-exposed animals indicated residue levels ranging between 20 and 30 microg/dl. In Experiment 2, adult female rats were treated daily with 0, 8, or 16 mg lead via gavage for 30 days before breeding with non-exposed males. Lead exposure in dams continued through gestation and until pups were weaned at postnatal day (PND) 21. At PND 60, male offspring received morphine or vehicle challenges identical to those described in Experiment 1. Animals perinatally exposed to dams receiving 16 mg lead daily demonstrated an enhanced behavioral response to morphine relative to control animals. Analysis of offspring blood indicated lead levels below detectable limits (<1 microg/dl) for all animals. The results suggest exposure to lead at environmentally relevant levels produces long-lasting changes in drug-induced behavior, and the developmental period in which lead exposure occurs is a significant contributor to the manifestation of these effects.

Histochemical demonstration of changes in the activity of hepatic phosphatases induced by experimental lead poisoning in male white rats (Rattus norvegicus).

Abstract: Seven hepatic phosphatases were histochemically investigated in male white rats (Rattus norvegicus) pretreated with chronic subtoxic doses of lead acetate. Lead has increased the activities of alka...

The interaction of lead exposure and arylsulfatase A genotype affects sulfatide catabolism in human fibroblasts

Abstract: Lead exposure causes cognitive and behavioral deficits in some affected children. We propose that a contributing mechanism for the neurological damage is that lead induces critically low levels of arylsulfatase A (ASA) at sensitive stages of nervous system development. It is hypothesized that the combined effects of a single nucleotide polymorphism (SNP) in human ASA which results in reduced levels of the enzyme, and lead concentrations which decrease ASA activity culminate in cellular enzymic activity that is below a critical threshold required for the maintenance of normal nervous system function. Human fibroblasts grown in the presence of 20 microM lead acetate exhibit a more than 60% decrease of cellular ASA enzyme protein. Lead treatment of cells from individuals with the SNP(s) of pseudodeficient ASA, but not those from subjects with the normal gene, results in a significant decrease in ability of the cells to desulfate sulfatide, the substrate of ASA. The decrease in the degree of sulfatide catabolism is consistent with possible enhanced lead-induced neurobehavioral effects in individuals homozygous for the pseudodeficiency polymorphism(s) of ASA.

Interaction of Dithane M-45 (mancozeb) and lead acetate during a teratogenicity test in rats.

Abstract: The teratogenic effects of lead acetate (Trial 1) and the possible teratogenic effect of this compound administered in combination with a fungicide containing 80% mancozeb (Trial 2) were studied in rats. The test substances were administered by gavage on Days 6-15 of gestation. In Trial 1, five groups were treated with lead acetate administered at doses of 0.1, 0.5, 1.0, 10.0 and 1000.0 mg/kg body weight (bwkg), respectively. In Trial 2, lead acetate was applied at doses of 0.1, 10.0 and 1000.0 mg/bwkg, respectively. In the latter case the dose of the pesticide was 750 mg/bwkg in all treated groups. Lead acetate was not teratogenic after a single administration. Combined administration of lead acetate and mancozeb gave rise to the following toxic effects: average maternal weight decreased during pregnancy, the ratio of live fetuses decreased after the two lowest doses, and fetal mortality increased in the lowest and in the highest dose groups. The ratio of fetal resorption was higher in all the treated groups than in the control group. A significant decrease occurred in average fetal and placental weight in each treated group as compared to the control. Maternal toxicity was expressed in paralysis of the hindlimbs in the two lowest dose groups. Maternal mortality was between 16.7 and 23.3% at the three dose levels. Phocomelia and hernia cerebri occurred as characteristic fetal developmental anomalies in all the treated groups. It is concluded that the joint administration of lead acetate and a mancozeb-containing fungicide can cause maternal toxicity, embryotoxicity and characteristic teratogenic effects.

Role of organic acids in lead patination

Abstract: A study is reported of the influence of organic acids (particularly acetic acid) on the development of lead patinas. Raman spectroscopy has been used to determine the chemical composition of patinas, while mass loss on descaling and scanning electron microscopy have followed their physical development. It was found that the mechanism of the patination process initially involved the formation of an oxide film which rapidly converted to a basic lead carbonate via normal and basic lead acetate intermediates. The high solubility of the acetate intermediaries influenced the morphology of the patina and increased the extent of its formation.