Lead and delinquency rates; A spatio-temporal perspective.

Juvenile delinquency has significant social costs for perpetrators, victims, and communities. To understand the distribution of delinquency offenses this study considers the spatial clustering of juvenile delinquency with lead, race, and neighborhood deprivation using a longitudinal ecological design (N = 4390) and a hierarchical model implemented in a Bayesian methodology that allows space-time interaction. The results show lead exposure is positively related to delinquency offense rates, and over time delinquency rates have become more concentrated in areas with higher levels of lead exposure and shares of Black or African American residents. The study emphasizes the isolation of neighborhoods with social problems and the importance of monitoring patterns of lead and crime at local levels as communities implement lead exposure mitigation programs.

Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats.

The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n = 6): one control and six treated with: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight, daily for 28 days by oral gavage. The rats were sacrificed and the blood and testes were used for further analysis of testosterone levels in serum, testicular essential metal levels and histological analysis. The Pb treatment led to a dose-dependent decrease of serum testosterone levels with a negative trend (BMDI 0.17-6.13 mg Pb/kg). Increase of Zn (dose-dependent, BMDI 0.004-19.7 mg Pb/kg) and Cu and a decrease of Mn testicular levels were also detected with unscathed histology of the testes. The presented results might be used in further evaluation of the point of departure in human health risk assessment for Pb.

The impact of cow dung augmentation on soil restoration and bio-accumulation of metals (Lead and Cadmium) in Pheretima posthuma (Annelida: Clitellata) / O impacto do aumento de esterco de vaca na restauração do solo e bioacumulação de metais (chumbo e cádmio) em Pheretima posthuma (Annelida: Clitellata)

To investigate the role of cow dung in soil reclamation and bio assimilation along with bio accumulation of heavy metals in earthworm (P. posthuma) (N=900) earthworms were used and treatment groups of CD-soil mixture of different proportion of cow dung were designed. Nonlethal doses of lead acetate and cadmium chloride were added in treatment groups. Mature P. posthuma were released in each experimental pot maintaining the favorable conditions. The pH, carbon, nitrogen, phosphorus, exchangeable cations, and heavy metal level of each mixture was evaluated. The results indicated that bio-assimilation of Pb and Cd by P. posthuma were significantly (P ˂ 0.01) higher in different soil-CD treatments compared to control. Highest bio-assimilation of both metals was observed in T¹ of both groups (Pb = 563.8 mg/kg and Cd = 42.95 mg/kg). The contents of both metals were significantly (P ˂ 0.05) lowered in casting. The nutrient concentration in the final castings of all soil-CD treatments were also equally transformed from less or insoluble to more soluble and available for plants, except for carbon level which increased with CD proportion. It is concluded that cow dung as organic matter has a positive effect on soil reclamation and bio-assimilation of metals by P. posthuma.

Para investigar o papel do esterco de vaca na recuperação do solo e bioassimilação, juntamente com a bioacumulação de metais pesados em minhocas (P. posthuma) (N = 900), minhocas foram usadas e grupos de tratamento de mistura CD-solo de diferentes proporções de esterco de vaca foram projetados. Doses não letais de acetato de chumbo e cloreto de cádmio foram adicionadas aos grupos de tratamento. P. posthuma maduros foram liberados em cada vaso experimental, mantendo as condições favoráveis. Foram avaliados o pH, carbono, nitrogênio, fósforo, cátions trocáveis e nível de metais pesados de cada mistura. Os resultados indicaram que a bioassimilação de Pb e Cd por P. posthuma foi significativamente (P ˂ 0,01) maior em diferentes tratamentos de solo-CD em relação ao controle. A maior bioassimilação de ambos os metais foi observada em T1 de ambos os grupos (Pb = 563,8 mg / kg e Cd = 42,95 mg / kg). O conteúdo de ambos os metais foi significativamente (P ˂ 0,05) reduzido na fundição. A concentração de nutrientes nas fundições finais de todos os tratamentos de solo-CD também foi igualmente transformada de menos ou insolúvel para mais solúvel e disponível para as plantas, exceto o nível de carbono que aumenta com a proporção de CD. Conclui-se que o esterco de vaca como matéria orgânica tem um efeito positivo na recuperação do solo e na bioassimilação de metais por P. posthuma.

Low-lead doses induce oxidative damage in cardiac tissue: Subacute toxicity study in Wistar rats and Benchmark dose modelling.

Exposure to toxic metals, including lead (Pb), were found as important risk factor for cardiovascular diseases. The aim of the study was to simulate low-level subacute Pb exposure scenario and to determine redox status, redox scores (OXY-score, damage score and protective score) and copper (Cu), zinc (Zn), iron (Fe) and manganese (Mn) levels in cardiac tissue of Wistar rats. Based on the obtained results we have established dose-toxic response relationship and derived Benchmark dose. The male Wistar rats were divided in seven groups (n = 6), six threated groups that received 0.1; 0.5; 1; 3; 7; 15 mg Pb/kg body weight/day for 28 days, by oral gavage and control group. The results of the presented study demonstrated that Pb affect cardiac tissue by inducing production of superoxide anion radical (O2.-) and consequently raising malondialdehyde (MDA) levels. The positive trend in OXY-score and damage score were determined. Effect size analysis showed that the main toxic effects were oxidative damage and elevation of MDA. The lowest BMD was calculated for MDA (2.2e-0.6 mg Pb/kg b.w./day). Obtained BMD may be useful in further assessing point of departure in the human health risks assessment of low-level Pb exposure scenario.

Distribution of Pb and Se in mouse brain following subchronic Pb exposure by using synchrotron X-ray fluorescence.

Lead (Pb) is a well-known neurotoxicant and environmental hazard. Recent experimental evidence has linked Pb exposure with neurological deterioration leading to neurodegenerative diseases, such as Alzheimer's disease. To understand brain regional distribution of Pb and its interaction with other metal ions, we used synchrotron micro-x-ray fluorescence technique (µ-XRF) to map the metal distribution pattern and to quantify metal concentrations in mouse brains. Lead-exposed mice received oral gavage of Pb acetate once daily for 4 weeks; the control mice received sodium acetate. Brain tissues were cut into slices and subjected for analysis. Synchrotron µ-XRF scans were run on the PETRA III P06 beamline (DESY). Coarse scans of the entire brain were performed to locate the cortex and hippocampus, after which scans with higher resolution were run in these areas. The results showed that: a) the total Pb intensity in Pb-exposed brain slices was significantly higher than in control brain; b) Pb typically deposited in localized particles of <10 um2 in both the Pb-exposed and control brain slices, with more of these particles in Pb-exposed samples; c) selenium (Se) was significantly correlated with Pb in these particles in the cortex and hippocampus/corpus callosum regions in the Pb-exposed samples, and the molar ratio of the Se and Pb in these particles is close to 1:1. These results indicated that Se may play a crucial role in Pb-induced neurotoxicity. Our findings call for further studies to investigate the relationship between Pb exposure and possible Se detoxification responses, and the implication in the etiology of Alzheimer's disease.

Environmentally relevant lead (Pb) water concentration induce toxicity in zebrafish (Danio rerio) larvae.

Early developmental stages of aquatic organisms including fish are inherently vulnerable to lead (Pb) and other water metal contaminants. However, reports on the deleterious effects of environmentally relevant Pb levels are limited. To this end, we exposed 2.5 h post fertilization (hpf) old zebrafish (Danio rerio) embryos to a range of Pb concentrations encompassing environmentally relevant levels (1, 10, 25, 50 and 100 µg/L Pb) until 96 hpf. Exposure negatively impacted the development and survival of zebrafish embryos by inducing embryo coagulation related mortalities in a concentration-dependent manner. At 24 hpf, the highest level of exposure (100 µg/L Pb) had impaired embryo activity characterized by reduced burst activity and the number of movements per minute made by embryos. At 72 hpf, newly hatched larvae exhibited adverse cardiovascular effects (100 µg/L Pb group) and neuromuscular effects (50 and 100 µg/L Pb groups). The antioxidant system dysregulation evidenced by downregulation of catalase, and upregulation of mRNA expression of glutathione S-transferase and cytochrome oxidase subunit I were observed. The pro-apoptotic tumour protein P53 (TP53) and the anti-apoptotic B cell lymphoma -2 (Bcl-2) mRNA expression levels were also affected. The former was downregulated across exposed groups and the latter was upregulated and downregulated in the groups with Pb concentrations less than 50 µg/L Pb and downregulated in 50 µg/L Pb, respectively. These findings suggest that Pb within environmentally relevant levels may be deleterious to developing zebrafish.

A Physiological behavior and tolerance of Lactuca sativa to lead nitrate and silver nitrate heavy metals / Comportamento fisiológico e tolerância de Lactuca sativa aos metais pesados nitrato de chumbo e nitrato de prata

This study goal to evaluate the effects of different concentrations of lead (Pb) and silver (Ag) on germination, initial growth and anatomical alterations of Lactuca sativa L. Plants use various mechanisms to reduce the impacts caused by anthropic action, such as xenobiotic elements of soils and water contaminated by heavy metals. These metals were supplied as lead nitrate and silver nitrate and the following treatments were established: control for both metals, maximum dose of heavy metals, for arable soils, allowed by the National Council of the Environment (Ag = 25 mg. Kg-¹, Pb = 180 mg. Kg-¹), double (Ag = 50 mg. Kg-¹, Pb = 360 mg. Kg-¹) and triple (Ag = 75 mg. Kg-¹, Pb = 540 mg. Kg-¹) of this dosage. Vigor and germination tests of the seeds and possible anatomical changes in the leaves and roots of lettuce plants were performed. The species showed a high capacity to germinate under Pb and Ag stress, and the germination was never completely inhibited; however, the germination decreased with increasing Pb concentrations, but not under Ag stress. The use of increasing doses of metals reduced seed vigor and increased chlorophyll content. An increase in biomass was also observed in plants from treatments submitted to Pb. The phytotoxic effects of metals were more pronounced at 15 days after sowing. Anatomically, L. sativa was influenced by metal concentrations, and had a reduction of up to 79.9% in root epidermis thickness at the highest Pb concentration, although some structures did not suffer significant changes. The results suggest that L. sativa presents tolerance to high concentrations of heavy metals, showing possible mechanisms to overcome the stress caused by these metals. In this research lettuce possibly used the mechanism of exclusion of metals retaining Pb and Ag in the roots preserving the photosynthetic apparatus in the aerial part of the plants. In general, the chemical element Pb was more toxic than Ag, in these experimental conditions.

Este estudo teve como objetivo avaliar os efeitos de diferentes concentrações de chumbo (Pb) e prata (Ag) na germinação, crescimento inicial e alterações anatômicas de Lactuca sativa L. As plantas utilizam vários mecanismos para reduzir os impactos causados pela ação antrópica, como elementos xenobióticos de solos e água contaminada por metais pesados. Esses metais foram fornecidos como nitrato de chumbo e nitrato de prata e foram estabelecidos os seguintes tratamentos:controle para ambos os metais, dose máxima de metais pesados, para solos cultiváveis, permitida pelo Conselho Nacional do Meio Ambiente (Ag = 25mg.Kg-¹, Pb = 180mg.Kg-¹), dobro (Ag = 50mg.Kg-¹, Pb = 360mg.Kg-¹) e triplo (Ag = 75mg.Kg-¹, Pb = 540 mg.Kg-¹) desta dosagem. Foram realizados testes de vigor e germinação das sementes e possíveis alterações anatômicas nas folhas e raízes das plantas de alface. A espécie apresentou alta capacidade de germinar sob estresse de Ag e Pb, e a germinação nunca foi completamente inibida; entretanto, a germinação diminuiu com o aumento das concentrações de Pb, mas não sob estresse de Ag. O uso de doses crescentes dos metais, reduziu o vigor das sementes e aumentou o teor de clorofila. Também foi observado aumento da biomassa nas plantas a partir dos tratamentos submetidos ao Pb. Os efeitos fitotóxicos dos metais foram mais acentuados aos 15 dias após a semeadura. Anatomicamente, L. sativa foi influenciada pelas concentrações de metais, e teve uma redução de até 79,9% na espessura da epiderme radicular na maior concentração de Pb, embora algumas estruturas não tenham sofrido alterações significativas. Os resultados sugerem que L. sativa apresenta tolerância a altas concentrações de metais pesados, mostrando possíveis mecanismos para superar o estresse causado por esses metais. Nesta pesquisa a alface possivelmente utilizou o mecanismo de exclusão de metais retendo Pb e Ag nas raízes preservando o aparato [...].

Lead (Pb)-induced oxidative stress mediates sex-specific autistic-like behaviour in Drosophila melanogaster.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterised by three main behavioural symptoms: abnormal social interaction, verbal and non-verbal communication impairments, and repetitive and restricted activities or interests. Even though the exact aetiology of ASD remains unknown, studies have shown a link between genetics and environmental pollutants. Heavy metal lead (Pb), the environmental pollutant, is associated with ASD. Pb may also exhibit sex-specific ASD behaviour, as has been demonstrated in the global human populations. Drosophila melanogaster as a model has been used in the present study to understand the involvement of Pb-induced oxidative stress in developing ASD behaviour. The larval feeding technique has been employed to administer different Pb concentrations (0.2-0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) antioxidants overexpressed or knockdown flies. Adult Drosophila (5-day old) were used for Pb content, biochemical, and behavioural analysis.Pb accumulated in the Drosophila brain induces oxidative stress and exhibited a human autistic-like behaviour such as reduced climbing, increased grooming, increased social spacing, and decreased learning and memory in a sex-specific manner.Pb-induced autistic-like behaviour was intensified in Sod or Cat-knockdown flies, whereas Sod or Cat-overexpressed flies overcome that behavioural alterations. These results unequivocally proved that Pb-induced oxidative stress causes ASD behaviour of humans in Drosophila. Thus, Drosophila is used as a model organism to analyse ASD-like human behaviour and underlines the importance of using antioxidant therapy in alleviating ASD symptoms in children.

Lead (Pb) induced Oxidative Stress as a Mechanism to Cause Neurotoxicity in Drosophila melanogaster.

The widespread use of lead (Pb) has caused global contamination, inevitable human exposure, and public health problems. Pb neurotoxicity has been linked to various human diseases, but its associated mechanism causing neurotoxicity is unknown. Drosophila melanogaster as a model organism has been used to study the mechanism involved in Pb-caused neurotoxicity and the potential role of antioxidants in ameliorating its harmful effects. The larval feeding technique was adopted to administer different concentrations of Pb (0.2-0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) overexpressing, and Sod or Cat knockdown flies to analyse Pb load, oxidative stress components, DNA damage, apoptosis and vacuolation in the brain. The results revealed that Pb accumulation in the Drosophila brain induces oxidative stress by generating reactive oxygen species (ROS) and lipid peroxidation (LPO), depleting antioxidant enzymes. Molecular docking studies have evidenced it. Pb directly binds to antioxidants and major grooves of DNA, leading to DNA damage. Increased DNA damage, apoptosis, vacuolation in brains of Pb-treated ORR, Sod, or Cat knockdown flies; and on the contrary, reduced oxidative DNA damage, apoptosis, and vacuolation in brains of Pb treated Sod or Cat overexpressed flies put forward that oxidative stress is the mechanism in Pb caused neurotoxicity.

Low concentrations of lead disturb phenotypical markers of the inflammatory and the anti-inflammatory profile of bone marrow-derived macrophages from BALB/c mice.

Lead (Pb) is a ubiquitous toxic metal that decreases resistance to infections, in which the macrophages have an essential role. Pb adverse effects on nitric oxide (NO-) production and variable effects on inflammatory cytokines in activated macrophages have been reported, but no effects have been reported in anti-inflammatory macrophages. We studied Pb (0.03-6 µg/dL equivalent to 0.014-2.89 µM) effects on the function of bone marrow-derived macrophages (BMDM) induced to either inflammatory or anti-inflammatory phenotypes, with LPS + IFNγ or IL-4+IL-13, respectively, and whether these effects are related. Pb did not induce cytotoxicity at any concentration in both macrophage phenotypes. In inflammatory BMDM, Pb (6 µg/dL) inhibited NO- production without affecting inducible nitric oxide synthase (iNOS) levels or basal arginase activity. At 3 and 6 µg/dL, Pb enhanced the major histocompatibility complex class II (MHC II) membrane expression but did not modify CD86 expression, TNFα, or IL-1ß production and secretion. In anti-inflammatory BMDM, Pb did not alter arginase activity, but at 3 and 6 µg/dL, increased TGF-ß1 and mannose receptor expression. Results showed that environmentally relevant concentrations of Pb alter functional outcomes or phenotypic markers of anti-inflammatory for the first time. The Pb effects on the inflammatory macrophages are not dependent on negative feedback resulting from the Pb effect on the anti-inflammatory phenotype. The Pb affected only some molecules or specific pathways related to both phenotypes. These effects could be related to Pb effects on immune defense against intracellular pathogens and allergy susceptibility.

Chronic lead exposure alters photic entrainment of locomotor activity rhythm and neuronal photoactivation in the suprachiasmatic nucleus of the adult rat.

Chronic lead (Pb) exposure affects the circadian physiological processes regulated by suprachiasmatic nucleus (SCN), which is synchronized (entrainment) by light. Disorders in the entrainment capacity of an organism alter its performance to interact with the environment, thus affecting its health status. The objectives of the present study were to evaluate whether chronic early Pb exposure affects the entrainment of the circadian rhythm of locomotor activity by light and to explore the possible mechanisms involved. Adult male Wistar rats, control and chronically exposed to Pb (320 ppm) in drinking water from gestation to adult age, were used. Assessment of the metal level showed a significant increase of Pb in the blood, hypothalamus and prefrontal cortex of the experimental rats. Continuous registrations of locomotor activity (12 h:12 h light-dark cycle) depicted that Pb induces important delay of this activity when the light was turned off. The Pb exposed animals entrained faster with a photoperiod delay of 6 h, (lights on at 13:00 h), and maintained the significant delay in the onset of activity at lights out. In continuous darkness, the animals were exposed to a light pulse at circadian time 23. This resulted in a significant decrease of photo-stimulated neurons (immunoreactivity to c-Fos) in the SCN of the metal-exposed animals. These results show that chronic early Pb exposure alters the photic entrainment of the rhythm of locomotor activity, which is evidenced by a significant decrease in both the number of photo-stimulated neurons and neuronal population (Nissl stain) of the SCN.

Lead (Pb) exposure induces physiological alterations in the serotoninergic and vasopressin systems causing anxiogenic-like behavior in Meriones shawi: Assessment of BDMC as a neuroprotective compound for Pb-neurotoxicity and kidney damages.

BACKGROUND: Studies have shown that lead (Pb) is one of hazardous heavy metals with various adverse effects on human health including mental health; Pb can induce psychiatric disorders like anxiety. In the present work, we examined the potential of bisdemethoxycurcumin (BDMC) as a neuroprotective agent against lead induced anxiety inMeriones shawi (M. shawi). METHODS: We asses, the potential of three consecutive day exposure to Pb (25 mg/kg body weight) in inducing anxiogenic effect, serotoninergic and vasopressinergic disruptions inM. shawi. This was done using neurobehavioral tests (open field, elevated plus maze), immunohistochemestry by anti-serotonin (5-HT), and anti-vasopressin (AVP) antibodies. We also measured the possible restorative potential of BDMC (30 mg/kg body weight), delivered by oral gavage. After that, a biochemical and histopathological studies were done. RESULTS: Our results showed that lead exposure for three consecutive days increases significantly the 5-HT-immunoreactivity in dorsal raphe nucleus (DRN) accompanied with a significant enhancement of AVP-immunoreactivity in the cell bodies and fibers in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. In the collecting tube, AVP binds to the V2 receptor of the epithelial cells and increases the water permeability. Our results showed clearly the epithelial cells degeneration after lead exposure, then we suggest that the increased AVP could be a response to the hydric balance disrupted after degenerative effect of lead exposure on epithelial cells. BDMC produced an anxiolytic effect in meriones. Moreover, it restored 5-HT and AVP immunoreactivity within studying nuclei. The biochemical and histopathological studies showed that Pb induced renal damages. In addition, BDMC restored the renal alterations. CONCLUSION: According to the obtained results, we suggest new pharmacological effects of BDMC; while it has an anxiolytic effect against Pb-induced anxiety by working on serotoninergic and vasopressinergic systems with an obvious restoration of the renal injuries induced by lead exposure.

On an extended understanding of the term "hormesis" for denoting alternating directions of the organism's response to increasing adverse exposures.

The authors propose to consider as hormesis phenomenon not only a realization of the Arndt-Schulze rule but any non-monotonic dose-response relationship for a certain outcome that is characterized by changing direction of a response between adjacent ranges of doses of an initiator of this response, the number of such ranges being two or more. This approach is illustrated with results of several in vitro experiments on different established cell lines exposed to CdS or PbS nanoparticles.

Differential Cytotoxicity of Haloaromatic Disinfection Byproducts and Lead Co-exposures against Human Intestinal and Neuronal Cells.

Disinfecting drinking water with chlorine inadvertently generates disinfection byproducts (DBPs) which can cause potential adverse health effects to humans. Haloaromatic DBPs are a group of emerging DBPs recently identified, suspected to be substantially more toxic than haloaliphatic DBPs but have not been extensively studied. Simultaneously, service pipelines made of lead materials are widely used in water distribution systems and become a source of dissolved lead (Pb) in tap water. In this study, we investigated the cytotoxicity of nine haloaromatic DBPs and lead ion (Pb2+), both separately as well as in combination, to human epithelial colorectal adenocarcinoma (Caco-2) and neuroblastoma (SH-SY5Y) cells. Results show that the cytotoxicity of the DBPs against Caco-2 cells followed the descending rank order of 2,4,6-triiodophenol ≅ 2,5-dibromohydroquinone > 2,4,6-tribromophenol > 3,5-dibromo-4-hydroxybenzaldehyde ≅ 2,4,6-trichlorophenol > 4-chlorophenol ≅ 3,5-dibromo-4-hydroxybenzoic acid > 2,6-dichlorophenol >5-chlorosalicylic acid, and the cytotoxicity of the DBPs against SH-SY5Y cells followed a similar rank order, 2,4,6-triiodophenol ≅ 2,5-dibromohydroquinone > 2,4,6-tribromophenol > 3,5-dibromo-4-hydroxybenzaldehyde ≅ 2,4,6-trichlorophenol > 4-chlorophenol > 3,5-dibromo-4-hydroxybenzoic acid > 2,6-dichlorophenol ≅ 5-chlorosalicylic acid. Lead in water did not change the toxicity of 3,5-dibromo-4-hydroxybenzoic acid (to either cell-type) or the toxicity of 4-chlorophenol (to the neuronal cell-type); but Pb2+ exhibited different degrees of synergistic effects with other tested DBPs. The synergism resulted in different rank orders of cytotoxicity against both intestinal and neuronal cells. These data indicate that future prioritization and regulation of emerging haloaromatic DBPs in drinking water should be considered in terms of their own toxicity and combinatorial effects with lead in water.

Force-velocity characteristics of isolated myocardium preparations from rats exposed to subchronic intoxication with lead and cadmium acting separately or in combination.

This investigation continues our study of the effects of Pb-Cd poisoning on the heart, extending the enquiry from isometric to auxotonic contractions, thereby examining the effect on the ability of myocardial tissues to perform mechanical work. Different shifts were revealed in myocardial force-velocity relations following subchronic exposure of rats to lead acetate and cadmium chloride acting separately, in combination, or in combination with a bioprotective complex (BPC). The experiments were conducted on isolated preparations of trabecules and papillary muscles of the right ventricle in physiological loading conditions and on isolated heart muscle contractile proteins examined by the in vitro motility assay. The results of the latter correlate with the shifts in the ratio of cardiac myosin isoforms. The amount of work performed by the myocardium was calculated on the basis of the tension-shortening loop area and was found to be similar in the preparations from all experimental groups. This fact presumably reflects adaptive capacity of the myocardial function even when contractility is damaged due to the metallic intoxication of a moderate severity. Some characteristics of rat myocardium altered by the impact of lead-cadmium intoxication became fully or partly normalized if intoxication developed against background administration of a bioprotective complex (BPC). Together with previously reported results obtained in the isometric mode of contractility, all these results strengthen the scientific foundations of risk assessment and risk management projects in the occupational and environmental conditions characterized by human exposure to lead and/or cadmium.

Effect of lead exposure and nutritional iron-deficiency on immune response: A vaccine challenge study in rats.

The prevalence of iron (Fe) deficiency and subclinical lead (Pb) toxicity is high in developing countries like India, and information on their potential additive effects on immune responses is scant. The current study assessed immune parameters in dual Pb-exposed\Fe-deficient weanling SD rats. Rats were fed a control (CD) or Fe-deficient (ID) diet for 4 weeks and then evaluated for hemoglobin (Hb) and serum Fe status. Then, half the rats in each group began to receive daily oral Pb exposure (25 mg/4 ml/kg BW; gavage) or vehicle for a further 4 weeks (while maintained on original respective diets). After the 4-weeks of dosing, rats were assessed for Hb and serum Fe, and for blood lead level (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity. At this point, half the rats in each group (now n = 8) were then vaccinated with tetanus toxoid (TT), and then two boosters at 2-week intervals. All the time, rats stayed on their original respective diets along with exposure to Pb on alternate days. At 2 weeks after the final booster, rats were euthanized and blood collected to assess total/specific IgG and IgM levels; mucosal (intestinal) IgA levels were also determined. Spleens were taken to assess CD4+ and CD8+ cell levels and for ex vivo measures of splenocyte proliferation/TH1 and TH2 cytokine formation. The results indicated significant lowering of Hb and serum Fe levels in ID rats and increased blood Pb and decreased ALAD activity in all Pb-exposed rats. Fe-deficiency alone induced significant increases in ALAD activity, but only in an absence of Pb. While there was no impact of any regimen on total or TT-specific IgG, significant decreases in mucosal IgA and TT-specific IgM were seen in ID-fed Pb-exposed rats. CD4+ cell levels were not impacted by treatment; CD8+ levels were increased in all ID/Pb-exposed rats. Ex-vivo splenocyte proliferation was significantly higher among vaccinated rats, as well as ID-fed Pb-exposed unvaccinated rats. Cytokine formation in all cases was highly variable. The results suggest that Fe deficiency compromised cell-mediated, mucosal, and/or humoral immune response-related endpoints and that Pb exposure during the deficiency further impacted these outcomes.

Morpho-functional alterations in lymphocytes and erythrocytes of Japanese quail due to prolonged in vivo exposure to heavy metal complexes.

BACKGROUND: Lead and cadmium are significant environmental pollutants that cause pathophysiological responses in many organs. Heavy metal absorption into many tissues is very fast due to a pronounced affinity for metallothioneins. METHOD: Japanese quail were exposed to different concentrations of metals (cadmium 0.20 mg/L and lead 0.25 and 0.50 mg/L) for 20 days. Erythrocytes (normal and hemolyzed) and lymphocytes (normal and altered) were monitored in this study. The analysis observed the percentage of normal and altered cells, as well as erythrocyte surface area. Cell counts were analyzed using light microscopy, while surface area and cytological changes in cells and nuclei were analyzed using licensed software. RESULTS: Different concentrations of metals have caused erythrocyte hemolysis as well as structural and morphological alterations in lymphocytes. Destruction of cell and nucleus membrane, changes in cell size, erythrocyte denucleation and reduced erythrocyte surface area were observed. Cadmium has caused erythrocyte hemolysis (29.30 %) and lymphocyte damage (92.10 %). Higher doses of lead resulted in greater damage to lymphocytes (63 %). Also, treatment with higher dose of lead produced a higher percentage of hemolyzed erythrocytes (19.20 %) in comparison to lower dose (9.90 %). CONCLUSION: The toxicity of heavy metals leads to reduced maturation of the blast, which causes the appearance of immature cells in peripheral circulation and severe destruction of blood cell membranes. Erythrocyte hemolysis can lead to anemia, while lymphocyte damage can lead to lymphocytopenia.

Variability in the Clearance of Lead Oxide Nanoparticles Is Associated with Alteration of Specific Membrane Transporters.

Lead oxide nanoparticles (PbONPs), upon their entry into the lungs via inhalation, induce structural changes in primary and secondary target organs. The fate and ultrastructural localization of PbONPs in organs is known to be dependent on the specific organ. Here, we focused on the differences in the ability to clear the inhaled PbONPs from secondary target organs and on molecular and cellular mechanisms contributing to nanoparticle removal. Mice were exposed to PbONPs in whole-body inhalation chambers. Clearance of ionic lead and PbONPs (Pb/PbONPs) from the lungs and liver was very effective, with the lead being almost completely eliminated from the lungs and the physiological state of the lung tissue conspicuously restored. Kidneys exposed to nanoparticles did not exhibit serious signs of damage; however, LA-ICP-MS uncovered a certain amount of lead located preferentially in the kidney cortex even after a clearance period. The concentration of lead in femurs, as representatives of the axial skeleton, was the highest among studied organs at all designated time points after PbONP exposure, and the clearance ability of lead from the femurs was very low in contrast to other organs. The organ-specific increase of ABC transporters expression (ABCG2 in lungs and ABCC3 in the liver) was observed in exposed animals, suggesting their involvement in removing Pb/PbONPs from tissues. Moreover, the expression of caveolins and clathrin displayed a tissue-specific response to lead exposure. Our results uncovered high variability among the organs in their ability to clear Pb/PbONPs and in the transporters involved in this process.

Bioaccessibility of antimony and other trace elements from lead shot pellets in a simulated avian gizzard environment.

Many studies have used grit (in the form of lead (Pb) pellets) presence in avian gizzards as an indicator of Pb shot exposure. However, due to nearly complete pellet absorption in gizzards or rapid passage of pellets, the absence of Pb shot presence in a gizzard does not confirm lack of Pb shot exposure. This study provides the basis for an additional technique to identify if elevated tissue Pb concentration is due to Pb shot exposure. Bioaccessibility of Pb and trace elements (Sb, As, and Sn) present in Pb shot were quantified to determine if any of these elements would be useful as a secondary marker of Pb shot exposure. An avian physiologically based extraction test (PBET) was used to determine pellet dissolution rate and bioaccessible concentrations of Pb, Sb, As, and Sn in a simulated gizzard environment. Of the three trace elements, only Sb concentrations (44-302 µg/mL) extracted into the gizzard solution were greater than environmental background levels (US soil average 0.48 µg/g); thus, no natural source likely provides this amount of Sb. Therefore, there is evidence that Sb can be extracted from Pb shot in bird gizzards at detectable concentrations (above natural background). While further studies are needed to delineate the mechanisms of absorption and distribution, this study lends credence to the hypothesis that Sb may be a useful marker of Pb shot exposure in biological tissues, particularly when Pb pellets are not present nor observed in avian tissues.

Immune status of Oreochromis niloticus subjected to long-term lead nitrate exposure and a Arthrospira platensis treatment trial.

In this study, the impacts of lead toxicity on Oreochromisniloticus were investigated. Additionally, the potential ameliorative effects of the Spirulina algae Arthrospira platensis were evaluated. The median lethal concentration (LC50) of PbNO3 was determined to be 143.3 mg/l for O. niloticus weighing 42 ± 2.5 g. O. niloticus were exposed to 10 % of the estimated PbNO3 LC50 for 12 weeks. The cumulative mortality rate (CMR) increased with exposure time. The results of assays for red blood cells (RBCs), haemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC) indicated that the exposed O. niloticus suffered from anaemia. The levels of liver enzymes, namely, aspartate transaminase (AST) and alanine transaminase (ALT), as well as metallothionein)MT(revealed deterioration of hepatic tissue. The activity of the antioxidant enzymes glutathione peroxidase (GPx) as well as catalase (CAT) was stimulated in the hepatic tissue of O. niloticus exposed to PbNO3 and in those treated with A. platensis. Based on the results of serum bactericidal activity (SBA) and oxidative burst activity (OBA) assays as well as challenge tests with Aeromonas hydrophila, it was clear that supplementation with 5 or 10 g/kg A. platensis significantly enhanced the fish immune status and decreased the mortality rate (MR). However, these effects were reduced by PbNO3 exposure with no differences in MR percentage. Therefore, it was clear that O. niloticus reared in lead nitrate-polluted water were immunosuppressed, while diet supplementation with A. platensis could ameliorate such impacts.