Novel plasma cytokines identified and validated in children during lead exposure according to the new updated BLRV DOI Creative Commons
Xuezhong Zhang,

Lingling Sun,

Mark Lloyd Granaderos Dapar

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 5, 2024

Lead is a pervasive environmental contaminant with significant health risks, particularly to children. It known for its neurotoxic and immunotoxic effects, causing developmental, cognitive, behavioral impairments. Despite extensive research, the mechanisms of lead toxicity remain unclear. Cytokines, which are critical in immune response inflammation, have emerged as potential biomarkers toxicity. The recent Centers Disease Control Prevention (CDC) update blood reference value (BLRV) 3.5 µg/dL emphasizes need explore novel mechanisms. study involved 100 healthy children aged 1 5 years, divided into two groups based on BLRV: elevated (≥ µg/dL) low (< µg/dL). research consisted phases: discovery validation. Plasma samples were analyzed using RayBio® Human Cytokine Antibody Arrays Enzyme-linked immunosorbent assay (ELISA) cytokine levels. Ethical approval was obtained, statistical analyses included t-tests, chi-squared tests, pearson correlations, multivariate logistic regression. Protein-protein interaction (PPI), Gene Ontology (GO) enrichment, Kyoto Encyclopedia Genes Genomes (KEGG) pathway conducted roles differentially expressed proteins (DEPs). No differences age, gender, or BMI between groups, but BLRV levels significantly higher group compared group. In phase, changes expression identified, including increased IL-6, IL-8, IL-17, decreased BDNF, BMP-4, IGF-1, IL-7, IL-10, Leptin. These findings validated second phase ELISA. Significant positive correlations found IL-17. Negative observed Multivariate regression confirmed that affects these PPI networks revealed DEPs had strong interactions multiple proteins, indicating their central role GO KEGG highlighted pathways related neurotoxicity inflammatory responses, "negative regulation myotube differentiation," "neurotrophin signaling pathway," "alcoholism." This provides insights cytokines offers comprehensive analysis involved. underscore importance early detection intervention updated thresholds.

Language: Английский

Influence of lead-induced toxicity on the inflammatory cytokines DOI Creative Commons

P. Harshitha,

Kalpita Bose,

Herman Sunil Dsouza

et al.

Toxicology, Journal Year: 2024, Volume and Issue: 503, P. 153771 - 153771

Published: March 1, 2024

Lead (Pb2+) is a hazardous heavy metal that pervasive in the human environment as result of anthropogenic activity, and poses serious health risks, particularly children. Due to its innumerable unique physical chemical properties, it has various applications; therefore, become common environmental pollutant. may cause oxidative stress, accumulating evidence indicates stress influences pathophysiology lead poisoning, also called plumbism. The immune system continually exposed pathogens xenobiotics, including metals such lead, appears be one most vulnerable targets. After being cells are subjected reactive oxygen species (ROS) production. When generation consumption ROS out equilibrium, cell structures, phospholipids disrupted leading lipid peroxidation. Various inflammatory signalling pathways activated consequence, along with reduced disease resistance, inflammation, autoimmunity, sensitization disruption cell-mediated humoral systems. negatively affects metabolism cytokines, interleukins IL-2, IL-1b, IL-6, IL-4, IL-8, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN), well expression functioning enzymes cyclooxygenases. However, toxicity depends on kind dosage, route entry, exposure period, age, host genetic predisposition.

Language: Английский

Citations

21

Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway DOI Creative Commons
Yunting Li,

Anfei Liu,

Kaiju Chen

et al.

Environment International, Journal Year: 2024, Volume and Issue: 184, P. 108479 - 108479

Published: Feb. 1, 2024

Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, effects short-chain fatty acids on and its mechanisms have not yet explored. In this study, results open field tests Morris water maze demonstrated that chronic exposure caused learning memory deficits anxiety-like symptoms in mice. The serum butyric acid content lead-treated mice decreased a dose-dependent manner, oral administration butyrate significantly improved cognitive impairment anxiety lead-exposed Moreover, alleviated neuroinflammation by inhibiting STAT3 signaling microglia. Butyrate also promoted expression acetyl-CoA synthetase ACSS2 hippocampal neurons, thereby increasing restoring both histone H3K9ac downstream BDNF. We median concentration high-lead humans was remarkably lower than low-lead (45.16 μg/L vs. 60.92 μg/L, P < 0.01), mediated relationship Montreal assessment scores, contribution rate 27.57%. conclusion, our suggest supplementation possible therapeutic strategy for lead-induced neurotoxicity.

Language: Английский

Citations

14

Isochlorogenic acid B alleviates lead-induced anxiety, depression and neuroinflammation in mice by the BDNF pathway DOI

Jia-Xue Shi,

Chao Cheng,

Hai-Nan Ruan

et al.

NeuroToxicology, Journal Year: 2023, Volume and Issue: 98, P. 1 - 8

Published: June 28, 2023

Language: Английский

Citations

13

Emerging roles of epigenetics in lead-induced neurotoxicity DOI Creative Commons
Zongqin Mei, Guofen Liu, Bo Zhao

et al.

Environment International, Journal Year: 2023, Volume and Issue: 181, P. 108253 - 108253

Published: Oct. 13, 2023

Lead is a common environmental heavy metal contaminant. Humans are highly susceptible to lead accumulation in the body, which causes nervous system damage and leads variety of diseases, such as Alzheimer's disease, Parkinson's autism spectrum disorder. Recent research has focused on mechanisms lead-induced neurotoxicity at multiple levels, including DNA methylation, histone modifications, non-coding RNAs, involved various diseases. We reviewed latest articles summarised emerging roles modification, RNAs neurotoxicity. Our summary provides theoretical basis directions for future prevention, diagnosis, treatment neurological

Language: Английский

Citations

11

Lead exposure induced transgenerational developmental neurotoxicity by altering genome methylation in Drosophila melanogaster DOI Creative Commons

Chunyan Wu,

Jie Wang, Xiaoxiao Luo

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 271, P. 115991 - 115991

Published: Jan. 17, 2024

Heavy metal toxicity is a significant global health concern, with particular attention given to lead (Pb) exposure due its adverse effects on cognitive development, especially in children exposed low concentrations. While Pb neurotoxicity has been extensively studied, the analysis and molecular mechanisms underlying transgenerational of exposure-induced remain poorly understood. In this study, we utilized Drosophila, powerful developmental animal model, investigate phenomenon. Our findings demonstrated that during stage had profound effect neurodevelopment F0 fruit flies. Specifically, observed loss correlation between terminal motor area muscle fiber area, along an increased frequency β-lobe midline crossing phenotype mushroom bodies. Western blot indicated altered expression levels synaptic vesicle proteins, decrease Synapsin (SYN) increase Bruchpilot (BRP) expression, suggesting changes release sites. These were corroborated by electrophysiological data, showing amplitude evoked excitatory junctional potential (EJP) spontaneous (mEJP) following exposure. Importantly, our results further confirmed resulting from grandparental exhibited effect. The F3 offspring displayed neurodevelopmental defects, function abnormalities, repetitive behavior despite lacking direct MeDIP-seq revealed alterations DNA methylation several associated genes (eagle, happyhour, neuroglian, bazooka, spinophilin) Pb. suggest modifications may underlie inheritance acquired phenotypic traits environmental

Language: Английский

Citations

4

Selenium protects against Pb-induced renal oxidative injury in weaning rats and human renal tubular epithelial cells through activating NRF2 DOI

Chongmei Tian,

Yu Qiu,

Yaping Zhao

et al.

Journal of Trace Elements in Medicine and Biology, Journal Year: 2024, Volume and Issue: 83, P. 127420 - 127420

Published: Feb. 27, 2024

Language: Английский

Citations

4

Bisphenol analogues induced social defects and neural impairment in zebrafish DOI
Xiyan Mu,

Zaiteng Liu,

Xiaoyu Zhao

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 899, P. 166307 - 166307

Published: Aug. 15, 2023

Language: Английский

Citations

9

Cadmium Exposure Is Associated with Behavioral Deficits and Neuroimmune Dysfunction in BTBR T+ Itpr3tf/J Mice DOI Open Access
Mohammed M. Alanazi, Mushtaq Ahmad Ansari, Ahmed Nadeem

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6575 - 6575

Published: March 31, 2023

Autism spectrum disorders (ASD) are neurobehavioral disabilities characterized by impaired social interactions, poor communication skills, and restrictive/repetitive behaviors. Cadmium is a common heavy metal implicated in ASD. In this study, we investigated the effects of Cd exposure on BTBR T+ Itpr3tf/J (BTBR) mice, an ASD model. We looked for changes repetitive behaviors sociability through experiments. also explored molecular mechanisms underlying exposure, focusing proinflammatory cytokines pathways. Flow cytometry measured IL-17A-, IL-17F-, IL-21-, TNF-α-, STAT3-, RORγt-expressing CD4+ T cells from spleens experimental mice. then used RT-PCR to analyze IL-17A, IL-17F, IL-21, TNF-α, STAT3, RORγ mRNA expression brain. The results behavioral experiments showed that significantly increased self-grooming marble-burying mice while decreasing interactions. number CD4+IL-17A+, CD4+IL-17F+, CD4+IL-21+, CD4+TNF-α+, CD4+STAT3+, CD4+RORγt+ cells, upregulating six molecules Overall, our suggest oral aggravates immune abnormalities animal These findings have important implications etiology provide further evidence metals contributing neurodevelopmental effects.

Language: Английский

Citations

7

Effects of Lead: Neurological and Cellular Perspective DOI
Chanchal Singh,

Raghubir Singh,

Apoorva Shekhar

et al.

Environmental contamination remediation and management, Journal Year: 2024, Volume and Issue: unknown, P. 17 - 33

Published: Jan. 1, 2024

Language: Английский

Citations

2

3-hydroxy-3′,4′,5′-trimethoxyflavone protects rats against lead-induced neurotoxicity via chelation and modulating oxidative stress, inflammatory and monoaminergic systems DOI Creative Commons
Varinder Singh, Richa Shri,

Parul Sood

et al.

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 118, P. 106278 - 106278

Published: June 8, 2024

Language: Английский

Citations

2