Multi-biological defects caused by lead exposure exhibit transferable properties from exposed parents to their progeny in Caenorhabditis elegans

Whether the multi-biological toxicity from lead exposure could be transferred to progeny has not been clarified. In the present study, we explored the Caenorhabditis elegans to analyze the multiple toxicities from lead exposure and their possibly transferable properties. The lead exposure could cause series of severe multi-biological defects with a concentration-dependent manner by affecting the endpoints of life span, development, reproduction and locomotion behaviors in nematodes. Moreover, most of these toxicities could be transferred to progeny from lead exposed animals and some of the defects in progeny appeared even more severe than in their parents, such as the body sizes and mean life spans. We summarized the defects caused by lead exposure into three groups according to their transferable properties or rescue patterns. That is, the defects caused by lead exposure could be largely, or partially, or became even more severe in progeny animals. Therefore, our results suggest that lead exposure can cause severely multi-biological defects, and most of these multiple toxicities can be considered as transferable for exposed animals in C. elegans.

Developmental Lead Exposure Alters the Distribution of Protein Kinase C Activity in the Rat Hippocampus

Chronic low-level lead (Pb) exposure in children is known to cause a deficit in learning and memory. In vitro studies have demonstrated that Pb altered protein kinase C (PKC) activityt Especially, hippocampal PKC has been correlated with performance in several learning tasks. The effects of Pb exposure on hippocampal PKC were investigated during development at various postnatal ages: postnatal day (PN) 7, 14, 28, and 56. Two-tenth % Pb acetate was administered to pregnant and lactating dams and then administered to weanling rats in drinking water. PKC activity was measured in both membrane and cytosolic fractions from the hippocampi of the controls and Pb-exposed animals. Pb-induced increase in PKC activity in the cytosolic fraction was obsereved in the PN56 rats. In contrast, PKC activity was decreased by Pb at PN7 in the membrane fraction. Furthermore, a significant decrease in the ratio of membrane to cytosolic PKC activity which is representative of PKC distribution was observed in the PN28 and PN56 Pb-exposed rats relative to the same-age controls. This study indicates that chronic Pb exposure during development influences hippocampal PKC activity and distribution. These changes may be involved in the subclinical neurotoxicity of chronic Pb exposure in young children.

Beta-amyloid precursor protein cleavage enzyme-1 expression in adult rat retinal neurons in the early period after lead exposure

Previous studies have reported that non-human primates and rodents exposed to lead during brain development may become dependent on the deposition of pre-determined β-amyloid protein （Aβ）,and exhibit upregulation of β-site amyloid precursor protein expression in old age.However,further evidence is required to elucidate the precise relationship and molecular mechanisms underlying the effects of early lead exposure on excessive Aβ production in adult mammals.The present study investigated the effects of lead exposure on expression of β-amyloid precursor protein cleavage enzyme-1 （BACE-1） in the rat retina and the production of Aβ in early development,using the retina as a window for studying Alzheimer＇s disease.Adult rats were intraocularly injected with different doses of lead acetate （10μmol/L,100μmol/L,1 mmol/L,10 mmol/L and 100 mmol/L）.The results revealed that retinal lead concentration,BACE-1 and its cleavage products β-C-terminal fragment and retina Aβ1-40 were all significantly increased in almost all of the lead exposure groups 48 hours later in a dose-dependent manner.The only exception was the 10μmol/L group.The distribution of BACE-1 in the retina did not exhibit obvious changes,and no distinctive increase in the activation of retinal microglia was apparent.Similarly,retinal synaptophysin expression did not exhibit any clear changes.These data suggest that lead exposure can result in the upregulation of retinal neuron BACE-1 expression in the early period of development and further increase the overproduction of Aβ1-40 in the retina.Our results provided novel insight into the molecular mechanisms underlying environmentally-induced Alzheimer＇s disease.

Potential Association of Lead Exposure During Early Development of Mice With Alteration of Hippocampus Nitric Oxide Levels and Learning Memory

Objective Chronic lead （Pb） exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains. Methods Sixty Balb/c mice aged l0 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05% 0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, （1） the weight of 0.075% group was significantly reduced （P〈0.05）; （2） The number of times in mice attaining the required standards in T-water maze test was lower in 0.075% group （P〈0.01）. No significant difference was found between experimental and control groups in open field test （P〉0.05）; （3） NO level of mouse hippocampus tissue was decreased in 0.075% group （P〈0.01）. Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

Lead Exposure and Oxidative Stress in Coal Miners

We aimed to investigate the short-term correlation between blood lead levels and oxidative stress generation in coal miners. The study involved 94 male coal miners from the Velenje Coal mine, arranged into four groups： three groups according to the number of consecutive working days, and a fourth control group. Miners who worked for three consecutive days had higher blood levels of lead and 8-isoprostane than the control group（P 〈 0.001）. Correlation between lead and 8-isoprostane was of medium strength（r = 0.512, P 〈 0.001）. Short-term lead environmental exposure can potentially harmful and should be considered when formulating improvements in working processes.

Maternal Lead Exposure Induces Down-regulation of Hippocampal Insulin-degrading Enzyme and Nerve Growth Factor Expression in Mouse Pups

Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease （AD）. Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life.

Assessment of Lead Exposures during Abrasive Blasting and Vacuuming in Ventilated Field Containments: A Case Study

Painting contractors have struggled with implementation and assessment of lead exposure controls leading to persistently elevated blood lead levels in this high-risk group of workers. The objective of this study was to assess the intensity of lead exposures based on commonly used air velocities inside field containment structures during abrasive blasting and vacuuming. Exposures were assessed over 14 days from April to July 2021 at a tainter gate and bridge lead paint removal project. Personal air samples, skin wipes, air velocity readings, and blood lead samples were collected. The geometric mean (GM) lead exposure for abrasive blasters and vacuumers was ≥4 × the OSHA Lead Permissible Exposure Limit (PEL) of 50 μg/m3. There was high variability in the personal lead exposures (Geometric standard deviation (GSD) 4.0 - 5.0). The GM hand wipe exposures exceeded a Dermal PEL of 500 μg/wipe (abrasive blaster 564 μg/wipe and vacuumer 754 μg/wipe). Residual lead was measured on workers’ hands in 67% of the post hand washing samples. Air velocities measured inside of the field containments ranged from 107 feet per minute to 229 feet per minute. The effect of air velocity on the concentration of lead on workers’ hands after work (F = 0.58, p = 0.35) and airborne lead concentration was not significant (F = 0.36, p = 0.48). Six of the eight workers’ blood lead levels increased after exposure to lead. There was a non-statistically significant relationship between lead remaining on workers’ hands after handwashing and an increase in blood lead level. This is the first study that assessed both ventilation flow rates used in the industrial painting industry and measurements of airborne and dermal (hands) lead exposures. For the projects evaluated, the collected exposure data indicate that air velocities frequently used in the industrial painting industry to ventilate field containment structures did not tend to prevent an increase in worker blood lead and were ineffective for adequately controlling elevated concentrations of airborne lead and preventing contact with workers’ hands.

Effect of occupational lead exposure on the blood pressure of lead-exposed workers

Objective To investigate the effect of occupational lead exposure on blood pressure and provide supportive evidence of health protection on lead-exposed workers.Methods 612 workers(452 lead-exposed workers,160workers as control)were recruited in the battery factory.The blood lead concentration and blood pressure were detected by occupational health examination and

Surveillance of Childhood Blood Lead Levels in 14 Cities of China in 2004-2006

Objective To investigate the blood lead level in children aged 0-6 years in urban areas of China. Methods Fourteen cities were selected as sites under surveillance. A total of 44 045 peripheral blood specimens were collected from 2004 to 2006, during which 15 727, 14 737, and 13 584 specimens were tested in 2004, 2005, and 2006, respectively. Tungsten atomizer absorption spectrophotometer was employed to determine blood lead level. Results The geometric mean blood lead level in the tested children was 47.10 μg/L with 10.10% ≥100 μg/L, 46.17 μg/L with 7.78% ≥100 μg/L, and 47.03 μg/L with 7.30% ≥ 100μg/L in 2004, 2005, and 2006, respectively. The blood lead levels seemed to tend to rise in parallel with the increase of age of the children and were higher in boys （48.84 μg/L, 47.56μg/L, and 47.78 μg/L in the 3 respective years） than in girls （45.00 μg/L, 44.53μg/L, and 46.13 μg/L）. Conclusion The blood lead levels in children in cities of China are lower than those in previous national studies, but higher than those in developed countries. Childhood lead poisoning remains a public health problem in China.

Increased hippocampal Disrupted-In-Schizophrenia 1 expression in mice exposed prenatally to lead

Disrupted-in-Schizophrenia 1 is a susceptibility gene for schizophrenia and other psychiatric disorders. Developmental lead exposure can cause neurological disorders similar to hyperactivity disorder, dyslexia and schizophrenia. In the present study, we examined the impact of developmental lead exposure, administered in vitro and in vivo, on hippocampal Disrupted-In- Schizophrenia 1 expression. Our results show that in cultured hippocampal neurons, in vitro exposure to 0.1-10 pM lead, inhibited neurite growth and increased Disrupted-In-Schizophrenia 1 mRNA and protein expression dose-dependently. In addition, blood lead levels in mice were increased with increasing mouse maternal lead （0.01-1 mM） exposure. Hippocampal neurons from these mice showed a concomitant increase in Disrupted-in-Schizophrenia 1 mRNA and protein expression. Overall our findings suggest that in vivo and in vitro lead exposure increases Disrupted-In-Schizophrenia 1 expression in hippocampal neurons dose-dependently, and consequently may influence synapse formation in newborn neurons.

Lead acetate in drinking water is toxic to hippocampal tissue Measuring relative protein changes using tissue array detection

BACKGROUND： Lead can cause structural changes in the hippocampus, followed by damage to learning and memory functions, but its specific mechanisms are not yet clear. OBJECTIVE： To observe long-term toxicity of high-dose lead in drinking water on hippocampal tissue in rats, and analyze the potential association of oxidative damage, cell apoptosis, and pathology. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Center for Medical Experiment, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from May 2007 to October 2008. MATERIALS; Rabbit anti Bcl-2, Bax, and inducible nitric oxide synthase （iNOS） polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA. An streptavidin-peroxidase immunohistochemistry kit and concentrated DAB kit were purchased from Beijing Zhongshan Biotechnology Company Limited, China. Crystal violet was purchased from Sigma, USA. METHODS： A total of 72 Wistar rats, aged 3 months, were randomly divided into control, low-, middle-, and high-dose lead groups, with 18 rats per group. Animal models were established through free drinking water contaminated by Pb2＋ for 1, 3, and 6 months, respectively. MAIN OUTCOME MEASURES： The general toxicity of lead was dynamically observed; the levels of Pb2＋ in the blood and brain tissue homogenete were detected using atomic absorption method; pathological changes were observed using hematoxylin-eosin staining and tigroid body staining; the protein expression levels of Bcl-2, Bax, and iNOS were dynamically observed using streptavidin-peroxidase immunohistochemistry of the hippocampus. RESULTS： Lead exposure reduced autonomic activities, produced a slumped appearance, slow responses, and lusterless fur, especially in the high-dose group. The amount of ingestion and hydroposia showed a decreasing trend, especially in middle- and high-dose groups. Lead levels in whole blood and brain homogenate were higher than controls （P 〈 0.01）. Lead caused degeneration of hippocampal neurons and pyknosis, with fewer tigroid bodies, especially in high-dose lead group. Bcl-2 expression decreased with increasing lead dose （P 〈 0.01）, whereas lead dose-dependently increased Bax levels （P 〈 0.01） and iNOS levels （P 〈 0.05）. CONCLUSION： High levels of Pb^2＋ may disrupt hippocampal structure by passing through the blood brain barrier. Oxidative damage and apoptosis may be a toxicity mechanism of Pb^2＋ on the hippocampus.

N-methyl-D-aspartate receptor subunit expression in memory-related brain areas of lead-exposed rats

Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced differences in NMDA subunit expression, and the correlation of lead poisoning with learning and memory, remain poorly understood. The present study measured differences in expression of NMDA receptor subunits NR1, NR2A, and NR2B in memory-related brain regions of rats who underwent different doses of lead exposure. Results demonstrated decreased NR1, NR2A, and NR2B subunit expressions in some memory-related brain areas. The inhibitory effect of 4.8 mmol/L lead exposure on hippocampal NR2B was most significant, although NR2A expression also significantly decreased following 14.4 mmol/L lead exposure. There was no difference in NR1 expression following exposure to 〈 4.8 mmol/L lead, although the inhibitory effect of 19.6 mmol/L lead exposure was strongest for NR1 expression in the hippocampus. Inhibitory avoidance test results revealed that greater concentrations of lead exposure resulted in decreased learning and memory. Therefore, lead toxicity was dependent on NMDA receptor subunit composition, and NR1, NR2A, and NR2B expressions were associated with time and concentration of lead exposure.

Higher rates of autism and attention deficit/hyperactivity disorder in American children:Are food quality issues impacting epigenetic inheritance?

In the United States,schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals.Pediatricians may play a key role in helping children access special education services.The number of children ages 6-21 in the United States receiving special education services increased 10.4%from 2006 to 2021.Children receiving special education services under the autism category increased 242%during the same period.The demand for special education services for children under the developmental delay and other health impaired categories increased by 184%and 83%respectively.Although student enrollment in American schools has remained stable since 2006,the percentage distribution of children receiving special education services nearly tripled for the autism category and quadrupled for the developmental delay category by 2021.Allowable heavy metal residues remain persistent in the American food supply due to food ingredient manufacturing processes.Numerous clinical trial data indicate heavy metal exposures and poor diet are the primary epigenetic factors responsible for the autism and attention deficit hyperactivity disorder epidemics.Dietary heavy metal exposures,especially inorganic mercury and lead may impact gene behavior across generations.In 2021,the United States Congress found heavy metal residues problematic in the American food supply but took no legislative action.Mandatory health warning labels on select foods may be the only way to reduce dietary heavy metal exposures and improve child learning across generations.

Health implication among occupational exposed workers in a chromium alloy factory, Thailand

This study was conducted to assess the occupational exposure and its health impact on the chromium alloy workers. Environmental and biological monitoring, noise and audiometry measurements were done to evaluate the exposure levels in the factory. A total of 112 non-smoking workers were monitored from July 2001 to August 2002 The results showed that most of the chromium and lead exposures in the factory were below the ACGIH-TWA of 50 μg/m 3 for chromium(Ⅵ) and OSHA-PEL of 50 μg/m 3 for lead. The highest chromium(7 25±0 16 μg/m 3) and lead(14 50±0 29 μg/m 3) concentrations were measured in the vibro room. The results indicated that elevated concentrations of chromium and lead were found in both blood and urine samples especially in those areas which were characterized by poor ventilation. The metal contents in blood and urine samples were significantly correlated with airborne metal concentrations in the factory. The result demonstrated that blood and urinary levels among workers were associated with increasing age and duration of exposure. The background noise level of the factory ranged from 67 6 to 89 2 dBA and was frequently higher than the threshold limit value for noise(90 dBA). According to the audiometric test, the exposed workers showed signs of noise-induced hearing loss. Noise at work continued to be an important factor to hearing loss among exposed workers. In our statistical analysis, a significant hearing loss was established on age effect and year of exposure among the workforce.

Inhibition of ROS elevation and damage to mitochondrial function prevents lead-induced neurotoxic effects on structures and functions of AFD neurons in Caenorhabditis elegans

Here we investigated the possible roles of oxidative stress in the formation of decreased thermotaxis to cultivation temperature in lead （Pb）-exposed nematodes Caenorhabditis elagans. Exposure to Pb at the examined concentrations decreased thermotaxis behaviors, and induced severe deficits in the structural properties of AFD sensory neurons. Meanwhile, Pb exposure caused the induction of severe oxidative damage, reactive oxygen species （ROS） production, and mitochondrial dysfunction in young adults. Moreover, pre-treatment with the antioxidants dimethyl sulfoxide （DMSO）, ascorbate and N-acetyl-L-cysteine （NAC）, used to inhibit both the ROS elevation and the mitochondrial dysfunction caused by Pb exposure, at the L2-1arval stage prevented the induction of oxidative damage and the formation of severe deficits in thermotaxis and structural properties of AFD sensory neurons in Pb-exposed young adults. Therefore, the formation of oxidative stress caused by Pb exposure may be due to both the induction of ROS elevation and damage to mitochondrial function, and oxidative stress may play a key role in inducing the neurotoxic effects on the structures and function of AFD sensory neurons in Pb-exposed nematodes.

Towards prenatal biomonitoring in Nanjing, China： lead and cadmium levels in the duration of pregnancy

Background Prenatal lead and cadmium exposure will not only influence the mother＇s organ systems,but also will provide an environment that may influence the fetus and neonate in a harmful way.In the present study,we detected the blood lead levels （BLLS） and cadmium levels for the duration of pregnancy and 6-12 weeks after delivery and to analyze the influencing factors of BLLs in healthy pregnant women.Methods A cohort study survey was carried out.We recruited 174 healthy pregnant women without pregnancy or obstetric complications or abnormal pregnancy outcomes as the gravida group,and 120 healthy non-pregnant women as the control group.Results The lead concentrations in the three pregnancy trimesters and in the postpartum period were：（5.98±2.43）,（5.54±2.01）,（5.59±1.97）,and （6.76±1.74） μg/dl; and （6.75±2.13） μg/dl in the control group.The cadmium concentrations in the three pregnancy trimesters and postpartum period were 1.61±0.45,1.63±0.46,1.64±0.49,and 1.67±0.57.We found that the BLLs in the gravida group were lower than in the control group during all three trimesters.Occupations,supplement nutritional elements （dietary supplements and nutritional （food） elements）,and the time of house painting could affect BLLs in pregnant women.Lead-related occupations,using cosmetics,and living in a house painted more recently than one year previously are risk factors of high BLLs among pregnant women,while calcium,iron,zinc,and milk supplements are protective factors.Conclusions These findings may help people,especially pregnant women,to reduce lead exposure via supplements of calcium,iron,zinc,and milk or avoiding contacting risk factors.