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Heavy Metal Toxicity in Humans 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 20332

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Special Issue Editors

Dr. Narasimham L. Parinandi

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Guest Editor

College of Medicine, Ohio State University, Columbus, OH 43210, USA
Interests: lipid biochemistry and lipidomics; bioactive lipid signaling; vascular biology; heavy metal toxicology

Dr. Jack T. Rogers

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Guest Editor

Neurochemistry Laboratory, Department of Psychiatry-Neuroscience, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, Boston, MA 02129, USA
Interests: 5' untranslated regions; alzheimer's disease; amyloid precursor protein; brain iron homeostasis; cytokin dysregulation; ferritins; iron; neurochemistry; neuropsychiatric disorders; neurotoxicity; parkinson's disease

Special Issue Information

Dear Colleagues,

Exposure to toxic heavy metals is a significant human health issue throughout the world. Heavy metals are used widely in chemical, agricultural, and technological applications and, thus, areas of the environment are contaminated heavily. Humans are often exposed to these heavy metals via occupational and dietary routes. Frequently, this exposure leads to detrimental health effects in humans. This Special Issue focuses on the toxicity of various heavy metals in humans. We welcome submissions, including original papers and reviews, on this topic.

Dr. Narasimham L. Parinandi
Dr. Jack T. Rogers
Guest Editors

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Published Papers (6 papers)

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Research

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19 pages, 1950 KiB

Open AccessArticle

Reference Values on Children’s Hair for 28 Elements (Heavy Metals and Essential Elements) Based on a Pilot Study in a Representative Non-Contaminated Local Area

by Roberto Ruiz, Carmen Estevan, Jorge Estévez, Carolina Alcaide, Miguel A. Sogorb and Eugenio Vilanova

Int. J. Mol. Sci. 2023, 24(9), 8127; https://doi.org/10.3390/ijms24098127 - 1 May 2023

Cited by 2 | Viewed by 2491

Abstract

Studies have been published, and laboratories offer services of measuring elements in hair as biomarkers of environmental exposure and/or control of essential elements (trace or macro). These reported values can have only sense if compared with adopted reference values. In this work, we propose provisional reference values based on a pilot child population. The concentrations of 28 elements were measured in children’s hair samples. An observational, descriptive, cross-sectional study was conducted in a typical child population in the Mediterranean region void of excessive pollution problems to analyze 419 hair samples of children aged 3–12 years. Children were selected by a simple random method from eight primary education schools in different municipal districts, which included urban, rural and industrial areas. Samples of around 100 mg were washed and acid digested by an optimized procedure. All measures were performed using ICP-MS with Sc, Y and Re as internal standards. The statistical analysis was performed by two approaches: (a) considering all the data and (b) without outliers (second-order atypical data) to compare them with other published studies. The distribution curves in all the elements studied were asymmetric and did not fit the theoretical normality distributions. Therefore, the analysis based on percentiles was more appropriate. In most elements, only slight differences were observed with sex or age, which did not justify proposing separate reference ranges. From the results of this study, provisional reference values are proposed following two criteria: (a) simple application of the table of percentiles built by removing outlier values and (b) values after a detailed analysis case-by-case, considering other data as the distribution profile and other published data of each element. Although the pilot sample was from a limited area, it was carefully selected to be representative of a general non-contaminated population. With this limitation, the proposed reference values might be useful for researchers and physicians until a wider geographical study is available for a large number of elements. Full article

(This article belongs to the Special Issue Heavy Metal Toxicity in Humans 2.0)

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12 pages, 3231 KiB

Open AccessCommunication

CoNiCrMo Particles, but Not TiAlV Particles, Activate the NLRP3 Inflammasome in Periprosthetic Cells

by Fenna Brunken, Tristan Senft, Maria Herbster, Borna Relja, Jessica Bertrand and Christoph H. Lohmann

Int. J. Mol. Sci. 2023, 24(6), 5108; https://doi.org/10.3390/ijms24065108 - 7 Mar 2023

Cited by 3 | Viewed by 1418

Abstract

Aseptic loosening is the main reason for arthroplasty failure. The wear particles generated at the tribological bearings are thought to induce an inflammatory tissue response, leading to bone loss and the subsequent loosening of the implant. Different wear particles have been shown to activate the inflammasome, thereby contributing to an inflammatory milieu in the direct vicinity of the implant. The aim of this study was to investigate whether the NLRP3 inflammasome is activated by different metal particles in vitro and in vivo. Three different cell lines representing periprosthetic cell subsets (MM6, MG63 and Jurkat) were incubated with different amounts of TiAlV or CoNiCrMo particles. The activation of the NLRP3 inflammasome was determined through the detection of the caspase 1 cleavage product p20 in a Western blot. The formation of the inflammasome was also investigated in vivo using immunohistological staining for ASC in primary synovial tissues as well as tissues containing TiAlV and CoCrMo particles and in vitro after the stimulation of the cells. The results show that the CoCrMo particles induced ASC more markedly, as a readout for inflammasome formation in vivo, compared to TiAlV particular wear. The CoNiCrMo particles also induced ASC-speck formation in all the tested cell lines, which was not induced by the TiAlV particles. The Western blot shows that NRLP3 inflammasome activation, measured through caspase 1 cleavage, was increased only by the CoNiCrMo particles in the MG63 cells. We conclude from our data that the activation of the inflammasome is mainly driven by CoNiCrMo particles and less by TiAlV particles, indicating that different inflammatory pathways are activated by the different alloys. Full article

(This article belongs to the Special Issue Heavy Metal Toxicity in Humans 2.0)

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13 pages, 1103 KiB

Open AccessArticle

An Insight into the Impact of Serum Tellurium, Thallium, Osmium and Antimony on the Antioxidant/Redox Status of PCOS Patients: A Comprehensive Study

by Manal Abudawood, Lulu Alnuaim, Hajera Tabassum, Hazem K. Ghneim, Mohammad A. Alfhili, Samyah T. Alanazi, Naif D. Alenzi and Sarah Alsobaie

Int. J. Mol. Sci. 2023, 24(3), 2596; https://doi.org/10.3390/ijms24032596 - 30 Jan 2023

Cited by 3 | Viewed by 2131

Abstract

Humans exploit heavy metals for various industrial and economic reasons. Although some heavy metals are essential for normal physiology, others such as Tellurium (Te), Thallium (TI), antimony (Sb), and Osmium (Os) are highly toxic and can lead to Polycystic Ovarian Syndrome (PCOS), a common female factor of infertility. The current study was undertaken to determine levels of the heavy metals TI, Te, Sb and Os in serum of PCOS females (n = 50) compared to healthy non-PCOS controls (n = 56), and to relate such levels with Total Antioxidant Capacity (TAC), activity of key antioxidant enzymes, oxidative stress marker levels and redox status. PCOS serum samples demonstrated significantly higher levels of TI, Te, Sb and Os and diminished TAC compared to control (p < 0.001). Furthermore, there was significant inhibition of SOD, CAT and several glutathione-related enzyme activities in sera of PCOS patients with concurrent elevations in superoxide anions, hydrogen and lipid peroxides, and protein carbonyls, along with disrupted glutathione homeostasis compared to those of controls (p < 0.001 for all parameters). Additionally, a significant negative correlation was found between the elevated levels of heavy metals and TAC, indicative of the role of metal-induced oxidative stress as a prominent phenomenon associated with the pathophysiology of the underlying PCOS. Data obtained in the study suggest toxic metals as risk factors causing PCOS, and thus protective measures should be considered to minimize exposure to prevent such reproductive anomalies. Full article

(This article belongs to the Special Issue Heavy Metal Toxicity in Humans 2.0)

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15 pages, 5451 KiB

Open AccessArticle

Extracellular Vesicles as Mediators of Nickel-Induced Cancer Progression

by Shan Liu, Angelica Ortiz, Aikaterini Stavrou, Angela R. Talusan and Max Costa

Int. J. Mol. Sci. 2022, 23(24), 16111; https://doi.org/10.3390/ijms232416111 - 17 Dec 2022

Cited by 2 | Viewed by 2210

Abstract

Emerging evidence suggests that extracellular vesicles (EVs), which represent a crucial mode of intercellular communication, play important roles in cancer progression by transferring oncogenic materials. Nickel (Ni) has been identified as a human group I carcinogen; however, the underlying mechanisms governing Ni-induced carcinogenesis are still being elucidated. Here, we present data demonstrating that Ni exposure generates EVs that contribute to Ni-mediated carcinogenesis and cancer progression. Human bronchial epithelial (BEAS-2B) cells and human embryonic kidney-293 (HEK293) cells were chronically exposed to Ni to generate Ni-treated cells (Ni-6W), Ni-transformed BEAS-2B cells (Ni-3) and Ni-transformed HEK293 cells (HNi-4). The signatures of EVs isolated from Ni-6W, Ni-3, HNi-4, BEAS-2B, and HEK293 were analyzed. Compared to their respective untreated cells, Ni-6W, Ni-3, and HNi-4 released more EVs. This change in EV release coincided with increased transcription of the EV biogenesis markers CD82, CD63, and flotillin-1 (FLOT). Additionally, EVs from Ni-transformed cells had enriched protein and RNA, a phenotype also observed in other studies characterizing EVs from cancer cells. Interestingly, both epithelial cells and human umbilical vein endothelial (HUVEC) cells showed a preference for taking up Ni-altered EVs compared to EVs released from the untreated cells. Moreover, these Ni-altered EVs induced inflammatory responses in both epithelial and endothelial cells and increased the expression of coagulation markers in endothelial cells. Prolonged treatment of Ni-alerted EVs for two weeks induced the epithelial-to-mesenchymal transition (EMT) in BEAS-2B cells. This study is the first to characterize the effect of Ni on EVs and suggests the potential role of EVs in Ni-induced cancer progression. Full article

(This article belongs to the Special Issue Heavy Metal Toxicity in Humans 2.0)

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Review

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27 pages, 1802 KiB

Open AccessReview

Current Levels of Environmental Exposure to Cadmium in Industrialized Countries as a Risk Factor for Kidney Damage in the General Population: A Comprehensive Review of Available Data

by Nazar M. Smereczański and Małgorzata M. Brzóska

Int. J. Mol. Sci. 2023, 24(9), 8413; https://doi.org/10.3390/ijms24098413 - 8 May 2023

Cited by 19 | Viewed by 4526

Abstract

The growing number of reports indicating unfavorable outcomes for human health upon environmental exposure to cadmium (Cd) have focused attention on the threat to the general population posed by this heavy metal. The kidney is a target organ during chronic Cd intoxication. The aim of this article was to critically review the available literature on the impact of the current levels of environmental exposure to this xenobiotic in industrialized countries on the kidney, and to evaluate the associated risk of organ damage, including chronic kidney disease (CKD). Based on a comprehensive review of the available data, we recognized that the observed adverse effect levels (NOAELs) of Cd concentration in the blood and urine for clinically relevant kidney damage (glomerular dysfunction) are 0.18 μg/L and 0.27 μg/g creatinine, respectively, whereas the lowest observed adverse effect levels (LOAELs) are >0.18 μg/L and >0.27 μg/g creatinine, respectively, which are within the lower range of concentrations noted in inhabitants of industrialized countries. In conclusion, the current levels of environmental exposure to Cd may increase the risk of clinically relevant kidney damage, resulting in, or at least contributing to, the development of CKD. Full article

(This article belongs to the Special Issue Heavy Metal Toxicity in Humans 2.0)

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12 pages, 1941 KiB

Open AccessReview

Adverse Human Health Effects of Chromium by Exposure Route: A Comprehensive Review Based on Toxicogenomic Approach

by Dong Yeop Shin, Sang Min Lee, Yujin Jang, Jun Lee, Cheol Min Lee, Eun-Min Cho and Young Rok Seo

Int. J. Mol. Sci. 2023, 24(4), 3410; https://doi.org/10.3390/ijms24043410 - 8 Feb 2023

Cited by 30 | Viewed by 6559

Abstract

Heavy metals are defined as metals with relatively high density and atomic weight, and their various applications have raised serious concerns about the environmental impacts and potential human health effects. Chromium is an important heavy metal that is involved in biological metabolism, but Cr exposure can induce a severe impact on occupational workers or public health. In this study, we explore the toxic effects of Cr exposure through three exposure routes: dermal contact, inhalation, and ingestion. We propose the underlying toxicity mechanisms of Cr exposure based on transcriptomic data and various bioinformatic tools. Our study provides a comprehensive understanding of the toxicity mechanisms of different Cr exposure routes by diverse bioinformatics analyses. Full article

(This article belongs to the Special Issue Heavy Metal Toxicity in Humans 2.0)

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