Adaptive epigenetic response of glutathione (GSH)-related genes against lead (Pb)-induced toxicity, in individuals chronically exposed to the metal

Devóz, Paula Pícoli; Reis, Mariana Bisarro dos; Gomes, Willian Robert; Maraslis, Flora Troina; Ribeiro, Diego Luís; Antunes, Lusânia Maria Greggi; Batista, Bruno Lemos; Grotto, Denise; Reis, Rui Manuel; Barbosa, Fernando; Barcelos, Gustavo Rafael Mazzaron

doi:10.1016/j.chemosphere.2020.128758

Cited by 19 publications

(7 citation statements)

References 51 publications

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“…Although to our knowledge, this study is the first that investigated possible interactive associations of GST genes ( GSTP1 , GSTM1 , and GSTT1 ) and ASD status in relation to BPbCs, our findings suggest associations of certain GST genotypes with significantly lower BPbCs in children with ASD than in TD controls that are in line with the literature, indicating a possible role of GST genes in detoxification of Pb [ 10 , 27 , 29 , 63 , 64 , 65 ] and/or their associations with ASD status [ 14 , 16 ]. For example, our findings show significant associations between the presence of at least one Val allele for the GSTP1 Ile105Val polymorphism and lower BPbCs in children with ASD than in TD controls, suggesting a possible role for the Val allele in detoxification of Pb.…”

Section: Discussionsupporting

confidence: 89%

Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder

Rahbar

Samms‐Vaughan

Kim

et al. 2022

Genes

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Glutathione S-transferases (GST) are involved in the detoxification of exogenous chemicals including lead (Pb). Using data from 344 pairs of autism spectrum disorder (ASD) cases and age- and sex-matched typically developing (TD) controls (2–8 years old) from Jamaica, we investigated the interaction between three GST genes and ASD status as determinants of blood Pb concentrations (BPbCs). We found that ASD cases had lower geometric mean BPbCs than TD children (1.74 vs. 2.27 µg/dL, p < 0.01). Using a co-dominant genetic model, ASD cases with the Ile/Val genotype for the GSTP1 Ile105Val polymorphism had lower GM BPbCs than TD controls, after adjusting for a known interaction between GSTP1 and GSTT1, child’s parish, socioeconomic status, consumption of lettuce, fried plantains, and canned fish (Ile/Val: 1.78 vs. 2.13 µg/dL, p = 0.03). Similarly, among carriers of the I/I or I/D (I*) genotype for GSTT1 and GSTM1, ASD cases had lower adjusted GM BPbCs than TD controls (GSTT1 I*: 1.61 vs. 1.91 µg/dL, p = 0.01; GSTM1 I*: 1.71 vs. 2.04 µg/dL, p = 0.01). Our findings suggest that genetic polymorphisms in GST genes may influence detoxification of Pb by the enzymes they encode in Jamaican children with and without ASD.

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Section: Discussionsupporting

confidence: 89%

Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder

Rahbar

Samms‐Vaughan

Kim

et al. 2022

Genes

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“…Through pathway analysis, 57 significant gene ontology enrichment terms were identified, including glutathione derivative biosynthetic process and nervous system development; thereby potentially bringing mechanistic insight into the toxic effects of lead exposure. The most recent study of lead exposure upon the epigenome is that of Devóz et al ( 75 ), who examined promoter methylation of four genes related to glutathione activity: Glutamate-Cysteine Ligase Catalytic Subunit ( GCLC) ; Glutathione Peroxidase 1 ( GPX1) ; Glutathione-Disulfide Reductase ( GSR); and GSTP1 . In workers exposed to lead, high blood lead levels were associated with reduced GCLC and GSTP1 methylation, potentially supporting the findings of Zhang et al and indicating that this pathway may be crucial to understanding biological response to lead exposure.…”

Section: Resultsmentioning

confidence: 99%

Toxicomethylomics revisited: A state-of-the-science review about DNA methylation modifications in blood cells from workers exposed to toxic agents

Jiménez-Garza

Ghosh

Barrow

et al. 2023

Front. Public Health

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IntroductionEpigenetic marks have been proposed as early changes, at the subcellular level, in disease development. To find more specific biomarkers of effect in occupational exposures to toxicants, DNA methylation studies in peripheral blood cells have been performed. The goal of this review is to summarize and contrast findings about DNA methylation in blood cells from workers exposed to toxicants.MethodsA literature search was performed using PubMed and Web of Science. After first screening, we discarded all studies performed in vitro and in experimental animals, as well as those performed in other cell types other than peripheral blood cells. Results: 116 original research papers met the established criteria, published from 2007 to 2022. The most frequent investigated exposures/labor group were for benzene (18.9%) polycyclic aromatic hydrocarbons (15.5%), particulate matter (10.3%), lead (8.6%), pesticides (7.7%), radiation (4.3%), volatile organic compound mixtures (4.3%), welding fumes (3.4%) chromium (2.5%), toluene (2.5%), firefighters (2.5%), coal (1.7%), hairdressers (1.7%), nanoparticles (1.7%), vinyl chloride (1.7%), and others. Few longitudinal studies have been performed, as well as few of them have explored mitochondrial DNA methylation. Methylation platforms have evolved from analysis in repetitive elements (global methylation), gene-specific promoter methylation, to epigenome-wide studies. The most reported observations were global hypomethylation as well as promoter hypermethylation in exposed groups compared to controls, while methylation at DNA repair/oncogenes genes were the most studied; studies from genome-wide studies detect differentially methylated regions, which could be either hypo or hypermethylated.DiscussionSome evidence from longitudinal studies suggest that modifications observed in cross-sectional designs may be transitory; then, we cannot say that DNA methylation changes are predictive of disease development due to those exposures.ConclusionDue to the heterogeneity in the genes studied, and scarcity of longitudinal studies, we are far away from considering DNA methylation changes as biomarkers of effect in occupational exposures, and nor can we establish a clear functional or pathological correlate for those epigenetic modifications associated with the studied exposures.

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“…We further assessed the levels of antioxidant enzymes in the lung tissue. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) serve as robust markers for evaluating the extent of oxidative stress-induced damage. , A significant decrease in enzyme activity of SOD and GSH-Px was noted, following the administration of CsPbBr 3 nanoparticles (Figure G,H). Similarly, treatment with the Pb(Ac) 2 group exhibited comparable alterations.…”

Section: Resultsmentioning

confidence: 99%

Lung Toxicity and Molecular Mechanisms of Lead-Based Perovskite Nanoparticles in the Respiratory System

Ding,

He,

Zhang

et al. 2023

ACS Appl. Mater. Interfaces

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Lead-based perovskite nanoparticles (Pb-PNPs) have found extensive applications across diverse fields. However, because of poor stability and relatively strong water solubility, the potential toxicity of Pb-PNPs released into the environment during their manufacture, usage, and disposal has attracted significant attention. Inhalation is a primary route through which human exposure to Pb-PNPs occurs. Herein, the toxic effects and underlying molecular mechanisms of Pb-PNPs in the respiratory system are investigated. The in vitro cytotoxicity of CsPbBr3 nanoparticles in BEAS-2B cells is studied using multiple bioassays and electron microscopy. CsPbBr3 nanoparticles of different concentrations induce excessive oxidative stress and cell apoptosis. Furthermore, CsPbBr3 nanoparticles specifically recruit the TGF-β1, which subsequently induces epithelial–mesenchymal transition. In addition, the biodistribution and lung toxicity of representative CsPbBr3 nanoparticles in ICR mice are investigated following intranasal administration. These findings indicate that CsPbBr3 nanoparticles significantly induce pulmonary inflammation and epithelial–mesenchymal transition and can even lead to pulmonary fibrosis in mouse models. Above findings expose the adverse effects and molecular mechanisms of Pb-PNPs in the lung, which broadens the safety data of Pb-PNPs.

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Adaptive epigenetic response of glutathione (GSH)-related genes against lead (Pb)-induced toxicity, in individuals chronically exposed to the metal

Cited by 19 publications

References 51 publications

Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder

Detoxification Role of Metabolic Glutathione S-Transferase (GST) Genes in Blood Lead Concentrations of Jamaican Children with and without Autism Spectrum Disorder

Toxicomethylomics revisited: A state-of-the-science review about DNA methylation modifications in blood cells from workers exposed to toxic agents

Lung Toxicity and Molecular Mechanisms of Lead-Based Perovskite Nanoparticles in the Respiratory System

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