International Journal of Environmental Research and Public Health
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2021
·Vol. 18
·期 22
·12051
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IF 3.39
Yifei Duan,Hua Shi,Yongmei Jiang
In order to understand current blood lead levels (BLLs), we investigated the BLLs of children in Sichuan Province from 2011 to 2020. We then monitored the treatment effects of calcium in children with high BLLs to assess their treatment status. Finally, we explored the effects of lead on Ca2+through in-situ experiments. Whole blood samples were used for BLL tests. The BLLs of 76,362 children aged 0–7 years were measured using atomic absorption spectrometry. The median BLL was 35 μg/L (interquartile range: 28–47). The BLLs were significantly higher in boys than in girls (p< 0.001). The BLLs generally decreased annually and increased with age. The overall prevalence of BLLs ≥ 100 μg/L was 1.20%. The children with high BLLs received subsequent check-ups, and the median time required for effective treatment was 18 months. We observed that lead exposure led to a gradual and persistent loss of Ca2+levels in neurons of mice brain slices, and the effect did not subside immediately even after the lead was removed. China has made rapid progress in pediatric healthcare, but the treatment status remains unsatisfactory. Because lead causes an irreversible loss of Ca2+, there is an urgent need to develop new standardized treatments to reduce the treatment duration.Keywords:blood lead levels;treatment status;calcium supplement;Ca2+imaging
研究领域:
公共卫生
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神经生物学
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儿科医学
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
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IF 9.8
Qian Liu,Cheng Xu,Jing Jin,Wenxiang Li,Jingjia Liang,Shijie Zhou,Zhenkun Weng,Yong Zhou,Xudong Liao,Aihua Gu
Lead (Pb) is widely used in industrial and daily-use consumer products. Early-life exposure may increase the risk of lead-related heart problems in childhood. However, the effects of early-life lead exposure on fetal heart development and long-term cardiac outcomes are unknown. In this study, pregnant ICR mice were exposed to lead acetate trihydrate (50 mg/kg/d) via oral gavage from gestation day 1.5 until offspring weaning. Thereafter, the second hit model was established, two groups of offspring (4 weeks old) were either administered sterile saline or Angiotensin II (Ang II) for 4 weeks until euthanasia. We investigated lead-induced offspring heart damage from embryonic period to adulthood by echocardiographic analysis, pathological H&E staining, and ultrastructural examination, as well as mitochondrial function detection. The results showed early-life lead exposure predisposed offspring mice to decreased ejection fraction, increased left ventricular volume, accompanied by hypertrophy and dilation, cardiomyocyte sarcomere dysplasia, abnormal mitochondrial structure, mitochondrial dysfunction, and decreased expression of key sarcomeric and mitochondrial genes, rendering them more susceptible to cardiac hypertrophy, vascular wall thickening, cardiac fibrosis, apoptosis, and heart failure induced by Ang II infusion. This study elucidates early-life low dose lead exposure compromises cardiac development and exacerbates second hit-induced cardiac pathological responses in adulthood, which furnishes crucial scientific evidence pertaining to the cardiac toxicity and risk evaluation associated with early-life exposure to lead.
研究领域:
毒理学
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心血管医学
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发育生物学
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DOI
PubMed
高影响因子
Jove-Journal of Visualized Experiments
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2021
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IF 1.355
Jie Ding,Rui Yan,Luna Wang,Qianlei Yang,Xiaoyun Zhang,Nan Jing,Yuanjie Wei,Hengdong Zhang,Yan An
Chemically induced bone loss due to lead (Pb) exposure could trigger an array of adverse impacts on both human and animal skeletal systems. However, the specific effects and mechanisms in zebrafish remain unclear. Alizarin red has a high affinity for calcium ions and can help visualize the bone and illustrate skeletal mineral mass. In this study, we aimed to detect lead acetate (PbAc)-induced bone loss in zebrafish larvae by using alizarin red staining. Zebrafish embryos were treated with a series of PbAc concentrations (0, 5, 10, 20 mg/L) between 2 and 120 h post fertilization. Whole-mount skeletal staining was conducted on larvae at 9 days post fertilization, and the total stained area was quantified using ImageJ software. The results indicated that the mineralized tissues were stained in red, and the stained area decreased significantly in the PbAc-exposure group, with a dose-dependent change in bone mineralization. This paper presents a staining protocol for investigating skeletal changes in PbAc-induced bone defects. The method can also be used in zebrafish larvae for the detection of bone loss induced by other chemicals.
研究领域:
毒理学
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发育生物学
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环境科学
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DOI
高影响因子
AQUACULTURE RESEARCH
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2022
·Vol. 53
·期 18
·6733-6744
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IF 2.184
Yudong Du,Haisu Liu,Biao Han,Yang Lei,Kun Qian,Anli Wang,Shengli Fu
Heavy metal lead (Pb) is a primary pollutant that pollutes aquatic environments and can be enriched in aquatic animals. Here, the effects of waterborne Pb on grass carp ( Ctenopharyngodon idella ) within 96 h of exposure were detected, and the association between microbiota alterations in the intestines and water was analysed. Results revealed that the intestinal barrier was damaged, including the intestinal morphology change, the structure-related genes ( villin-1 and Claudin-7 ) expression down-regulation, the antioxidant ( GST and GSH-Px ) and immune-related genes ( TNF-α and IL-8 ) expression up-regulation. The MiSeq sequencing data revealed a decrease in diversity and an increase in microbiota richness in the intestines and water after Pb exposure. Linear discriminant analysis (LDA) results revealed an increase in the dominant bacteria (P _proteobacteria and C _Gammaproteobacteria ) in the water, which enriched bacteria in the intestines. Canonical correlation analysis (CCA) found that there were correlations between intestinal microbiota and water microbiota, intestinal structure morphology and immune factors. Based on these results, we speculated that the effects of Pb on the grass carp intestinal barrier may be related to changes in the intestinal structure of grass carp and the water microbial community. These findings improve our understanding of the effects of heavy metals on the fish–microbe relationships after polluting aquatic habitats.
研究领域:
环境科学
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水生毒理学
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微生物学
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DOI
高影响因子
Toxicology Research
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2021
·Vol. 10
·期 4
·667-676
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IF 3.524
Liu Rundong,Wang Yawei,Bai Lin,Wang Ruike,Wu Yingying,Liu Mengchen,Li Qiong,Ba Yue,Zhang Huizhen,Zhou Guoyu,Cheng Xuemin,Huang Hui
Sirtuin 1 (SIRT1), the NAD-dependent histone deacetylase, has been extensively investigated due to its cognitive protective effect. Studies suggest microRNAs (miRNAs) and histone modifications are key epigenetic regulators of gene expression and play important role in brain development. We previously showed that cognitive impairment by lead (Pb) was associated with downregulation of SIRT1, but the epigenetic role of this is unclear. Thus, we exposed 4-week-old male mice to 0.2% lead acetate solution for three months, and subsequently extracted brain homogenate from mice cortex and hippocampus at the age of 1, 4, and 16 months, respectively. In this study, we found that the protein level of SIRT1 was inhibited in the hippocampus and cortex of 16-month-old aged mice exposed to Pb. Moreover, changes in the levels of miR-138-5p and miR-141-3p, which were considered to the mechanistic target of SIRT1 by bioinformatic analysis, were negative correlations SIRT1 protein expression. We also found miR-34c-3p expression was increased in the cortex of mice at the age of 16 months. Collectively, our results showed the expression of neural SIRT1 and three selected microRNAs at different age nodes of mice for the first time of following Pb exposure. Our results suggest that additional efforts should focus on the consequences of early Pb exposure from an epigenetic perspective.
研究领域:
神经科学
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分子生物学
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毒理学
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表观遗传学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2023
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IF 5.2
Haisu Liu,Hang Zhang,Qianxun Yu,Sanshan Zhang,Xiao Tu,Fenghong Zhuang,Shengli Fu
Lead (Pb) is a hazardous pollutant in water environments that can cause significant damage to aquatic animals and humans. In this study, crucian carp ( Carassius auratus ) were exposed to waterborne Pb for 96 h; then, histopathological analysis, quantitative qPCR analysis, and 16S high-throughput sequencing were performed to explore the effects of Pb on intestinal bioaccumulation, structural damage, oxidative stress, immune response, and microbiota imbalance of C. auratus . After Pb exposure, the intestinal morphology was obviously damaged, including significantly increasing the thickness of the intestinal wall and the number of goblet cells and reducing the depth of intestinal crypts. Pb exposure reduced the mRNA expressions of Claudin-7 and villin-1 while significantly elevated the level of GST, GSH, CAT, IL-8, IL-10, IL-1 , and TNF- α. Furthermore, 16S rRNA analysis showed that the Shannon and Simpson indices decreased at 48 h after Pb exposure, and the abundance of pathogenic bacteria (Erysipelotrichaceae, Weeksellaceae, and Vibrionaceae) increased after Pb exposure. In addition, the correlation network analysis found that Proteobacteria were negatively correlated with Firmicutes and positively correlated with Bacteroidetes . Functional prediction analysis of bacteria speculated that the change in intestinal microbiota led to the PPAR signaling pathway and peroxisome function of the intestine of crucian carp was increased, while the immune system and membrane transport function were decreased. Finally, canonical correlation analysis (CCA) found that there were correlations between the intestinal microbiota, morphology, antioxidant factors, and immune factors of crucian carp after Pb exposure. Taken together, our results demonstrated that intestinal flora dysbiosis, morphological disruption, oxidative stress, and immune injury are involved in the toxic damage of Pb exposure to the intestinal structure and function of crucian carp. Meanwhile, Pb exposure rapidly increased the abundance of pathogenic bacteria, leading to intestinal disorders, further aggravating the damage of Pb to intestinal structure and function. These findings provide us a basis for the link between gut microbiome changes and heavy metal toxicity, and gut microbiota can be used as biomarkers for the evaluation of heavy metal pollution in future.
研究领域:
环境科学
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水产养殖学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2022
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IF 4.52
Haisu Liu,Kun Qian,Sanshan Zhang,Qianxun Yu,Yudong Du,Shengli Fu
Lead (Pb) is one of the most common trace metals in water, and its high concentration in the environment can cause harm to aquatic animals and humans. In the present study, the effects of Pb exposure (3.84 mg/kg) on the morphology, digestive enzyme activity, immune function and microbiota structure of silver carp ( Hypophthalmichthys molitrix ) intestines within 96 h were detected. Moreover, the correlation between them was analyzed. The results showed that Pb exposure on the one hand severely impaired the intestinal morphology, including significantly shortening the intestinal villi's length, increasing the goblet cells' number, causing the intestinal leukocyte infiltration , and thickening the intestinal wall abnormally, on the other hand, increasing the activity of intestinal digestive enzyme (trypsin and lipase). In addition, the mRNA expressions of structure-related genes ( Claudin-7 and villin-1 ) were down-regulated, and the immune factors genes ( IL-8 , IL-10 and TNF-α ) were up-regulated after Pb exposure. Furthermore, data of the MiSeq sequencing showed that the abundance of membrane transport , immune system function and digestive system of silver carp intestinal microbiota all decreased, while cellular antigens increased. Finally, the canonical correlation analysis (CCA) showed that there were correlations between silver carp's intestinal microbiota and intestinal morphology and immune factors. In conclusion, it is speculated that the entry of Pb into the intestine leads the microbiota dysbiosis , affects the intestinal immunity and digestive function , and further damages the intestinal barrier of silver carp.
研究领域:
环境科学
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水生毒理学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
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2020
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IF 3.171
Jian-Zhu Bo,Ling Xue,Shuang Li,Jing-Wen Yin,Zheng-Yao Li,Xi Wang,Jun-Feng Wang,Yan-Shu Zhang
Although exogenous D-serine has been applied as a neural regulatory intervention in many studies, the role played by D-serine in hippocampal injuries caused by lead exposure remains poorly understood. Rat models of chronic lead exposure were established through the administration of 0.05% lead acetate for 8 weeks. Simultaneously, rats were administered 30 or 60 mg/kg D-serine, intraperitoneally, twice a day. Our results showed that D-serine treatment shortened the escape latency from the Morris water maze, increased the number of times that mice crossed the original platform location, and alleviated the pathological damage experienced by hippocampal neurons in response to lead exposure. Although D-serine administration did not increase the expression levels of the N-methyl-D-aspartate receptor subtype 2B (NR2B) in the hippocampi of lead-exposed rats, 60 mg/kg D-serine treatment restored the expression levels of NR2A, which are reduced by lead exposure. These findings suggested that D-serine can alleviate learning and memory impairments induced by lead exposure and that the underlying mechanism is associated with the increased expression of NR2A in the hippocampus. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China (approval No. LX2018155) on December 21, 2018.
研究领域:
神经科学
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毒理学
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药理学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
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IF 7.6
Jun Li,Meixin Hu,Yingying Liu,Rongrong Lu,Weijun Feng
Heavy metals, such as Lead (Pb), are ubiquitous environmental pollutants that is a considerable problem worldwide. Increasing evidences suggest that Pb exposure negatively impact central nervous system. However, the exact toxic mechanism of Pb on early human brain development remain unclear due to the limitations of animal models and 2D cell models. In this study, we used human cortical organoids to reveal that Pb had specific early neurodevelopmental toxicity during the neural differentiation stage. We observed that short-term Pb exposure (10 days) is sufficient to induce premature neuronal differentiation. Mechanistically, Pb exposure downregulates the Wnt signaling in cortical organoids, and the activation of Wnt signaling reverses the neurodevelopmental phenotype. In support, Pb exposure during pregnancy lead to premature neuronal differentiation and reduced neurogenesis in mice. In conclusion, our study reveals the neuropathogenesis of Pb exposure and uncovers the potential intervention role of Wnt activation.
研究领域:
毒理学
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神经科学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Anfei Liu,Yunting Li,Lifan Li,Kaiju Chen,Meitao Tan,Fei Zou,Xingmei Zhang,Xiaojing Meng
Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.
研究领域:
神经科学
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毒理学
·
微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Lin Zhang,Yin Lin,An-Xin Lu,Jun-Xia Liu,Jing Li,Chong-Huai Yan
Today's women of childbearing age with a history of high lead (Pb) exposure in childhood have large Pb body burdens, which increases Pb release during pregnancy by promoting bone Pb mobilisation. The purpose of this study was to investigate the metabolic mechanisms underlying bone Pb mobilisation and explore the bone metabolism-related pathways during pregnancy. Drinking water containing 0.05% sodium acetate or Pb acetate was provided to weaned female rats for 4 weeks followed by a 4-week washout period, and then rats were co-caged with healthy males of the same age until pregnancy. Blood and bone tissues of the female rats were collected at gestational day (GD) 3 (early pregnancy), GD 10 (middle pregnancy), and GD 17 (late pregnancy), respectively. Pb and calcium concentrations, biomarkers for bone turnover, bone microstructure, serum metabolomics, and metabolic indicators were intensively analyzed. The results demonstrated that pre-pregnancy Pb exposure elevated blood lead levels (BLLs) at GD17, accompanied by a negative correlation between BLLs and trabecular bone Pb levels. Meanwhile, Pb-exposed rats had low bone mass and aberrant bone architecture with a larger number of mature osteoclasts (OCs) compared to the control group. Moreover, the metabolomics uncovered that Pb exposure caused mitochondrial dysfunction, such as enhanced oxidative stress and inflammatory response, and suppressed energy metabolism. Additionally, the levels of ROS , MDA, IL-1β, and IL-18 involved in redox and inflammatory pathways of bone tissues were significantly increased in the Pb-exposed group, while antioxidant SOD and energy metabolism-related indicators including ATP levels, Na + -K + -ATPase, and Ca 2+ -Mg 2+ -ATPase activities were significantly decreased. In conclusion, pre-pregnancy Pb exposure promotes bone Pb mobilisation and affects bone microstructure in the third trimester of pregnancy, which may be attributed to OC activation and mitochondrial dysfunction.
研究领域:
毒理学
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生殖生物学
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代谢组学
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骨生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
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2020
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IF 3.292
Zuntao Wu,Lin Bai,Runqi Tu,Lijie Zhang,Yue Ba,Huizhen Zhang,Xing Li,Xuemin Cheng,Wenjie Li,Hui Huang
Lead (Pb) is recognized as a potent inducer of synaptic toxicity generally associated with reduced synaptic transmission and increased neuronal fiber excitability, becoming an environmental risk for neurodegenerative processes. Despite numerous toxicological studies on Pb have been directed to the developing brain, attention concerning long-term consequences of pubertal chronic Pb exposure on neuronal activity is still lacking. Thus, we exposed 4-week-old male mice to 0.2 % lead acetate solution for one month, then, conducted behavioral tests or extracted brain homogenate from mice prefrontal cortex (PFC) and hippocampus at the age of 4, 13 and 16-month-old respectively. Our results showed that treated mice exhibited an evident increase in latency to reach platform following pubertal Pb exposure and aging. The increase of 8-OHdG revealed evident neural DNA oxidative damage across time upon pubertal Pb exposure. In the hippocampus of lead exposed mice at three age nodes, the expression of brain-derived neurotrophic factor precursor (proBDNF) increased, while that of mature BDNF (mBDNF), cAMP-response element binding protein (CREB) and phosphorylated CREB (pCREB) decreased compared with the control group. Furthermore, the expression of BACE1 protein and tau phosphorylation level in PFC and hippocampus increased, APP mRNAs in PFC and prolonged induction of BACE1 in hippocampus. Our results show that chronic Pb exposure from pubertal stage onward can either initiate divergent synaptic-related gene expression patterns in adulthood or trigger time-course of neurodegenerative profile within the PFC or hippocampus, which can contribute consistent deficits of cognition across subsequent age-nodes.
研究领域:
神经毒理学
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神经科学
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分子生物学
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行为科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）