Topical Collection "Heavy Metals Toxicology"

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A topical collection in Toxics (ISSN 2305-6304).

Editor

Collection Editor
Prof. Dr. Wayne Briner

Department of Psychology, Ashford University, 8620 Spectrum Center Blvd, San Diego, CA 92123 USA
Phone: 858-705-2294
Interests: neurotoxicology; heavy metals; teratology; behavioral teratology

Topical Collection Information

Dear Colleagues,

Heavy metals such as lead and mercury continue to effect human and environmental health. Heavy metals not only persist in the environment but continue to be produced and released by mining, manufacturing and environmental processes. Human exposure persists and even expands as humankind develops more manufacturing and mining processes, encroaches on more land area, and develops uses for a wider variety of heavy metals. Progress has been made in understanding the toxicology of metals, prevention has been improved and treatment refined over the years.  Despite these advances more research needs to be done.

We invite contributors to this collection of Toxics that will focus on heavy metal toxicology. We invite all papers addressing this problem.  Theoretical papers will also be considered. We especially encourage papers examining metal-metal interactions and pharmacologic treatment of heavy metal exposure.

Professor Dr. Wayne Briner
Collection Editor

Manuscript Submission Information

Manuscripts for the topical collection can be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on this website. The topical collection considers regular research articles, short communications and review articles. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page.

Please visit the Instructions for Authors page before submitting a manuscript. For the first few issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections. For further details see here.


Keywords

  • heavy metal
  • interactions
  • chelation
  • lead
  • mercury
  • treatment
  • molecular mechanisms
  • antagonist

Published Papers (10 papers)

2015

Jump to: 2014

Open AccessArticle The Role of the Component Metals in the Toxicity of Military-Grade Tungsten Alloy
Toxics 2015, 3(4), 499-514; doi:10.3390/toxics3040499
Received: 9 November 2015 / Revised: 1 December 2015 / Accepted: 2 December 2015 / Published: 8 December 2015
Cited by 1 | PDF Full-text (1420 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tungsten-based composites have been recommended as a suitable replacement for depleted uranium. Unfortunately, one of these mixtures composed of tungsten (W), nickel (Ni) and cobalt (Co) induced rhabdomyosarcomas when implanted into the leg muscle of laboratory rats and mice to simulate a [...] Read more.
Tungsten-based composites have been recommended as a suitable replacement for depleted uranium. Unfortunately, one of these mixtures composed of tungsten (W), nickel (Ni) and cobalt (Co) induced rhabdomyosarcomas when implanted into the leg muscle of laboratory rats and mice to simulate a shrapnel wound. The question arose as to whether the neoplastic effect of the mixture could be solely attributed to one or more of the metal components. To investigate this possibility, pellets with one or two of the component metals replaced with an identical amount of the biologically-inert metal tantalum (Ta) were manufactured and implanted into the quadriceps of B6C3F1 mice. The mice were followed for two years to assess potential adverse health effects. Implantation with WTa, CoTa or WNiTa resulted in decreased survival, but not to the level reported for WNiCo. Sarcomas in the implanted muscle were found in 20% of the CoTa-implanted mice and 5% of the WTa- and WCoTa-implanted rats and mice, far below the 80% reported for WNiCo-implanted mice. The data obtained from this study suggested that no single metal is solely responsible for the neoplastic effects of WNiCo and that a synergistic effect of the three metals in tumor development was likely. Full article
Open AccessReview Speciation in Metal Toxicity and Metal-Based Therapeutics
Toxics 2015, 3(2), 170-186; doi:10.3390/toxics3020170
Received: 16 March 2015 / Revised: 8 April 2015 / Accepted: 22 April 2015 / Published: 28 April 2015
PDF Full-text (792 KB) | HTML Full-text | XML Full-text
Abstract
Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual [...] Read more.
Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual elements, but detailed chemical structures are. As a broad generalization, the metallic form of an element is inert, and the ionic salts are the species that show more significant bioavailability. Yet the salts and other chelates of a metal ion can give rise to quite different toxicities, as exemplified by a range of carcinogenic potential for various nickel species. Another important distinction comes when a metallic element is organified, increasing its lipophilicity and hence its ability to penetrate the blood brain barrier, as is seen, for example, with organic mercury and tin species. Some metallic elements, such as gold and platinum, are themselves useful therapeutic agents in some forms, while other species of the same element can be toxic, thus focusing attention on species interconversions in evaluating metal-based drugs. The therapeutic use of metal-chelating agents introduces new species of the target metal in vivo, and this can affect not only its desired detoxification, but also introduce a potential for further mechanisms of toxicity. Examples of therapeutic iron chelator species are discussed in this context, as well as the more recent aspects of development of chelation therapy for uranium exposure. Full article
Open AccessReview Live and Let Die: Roles of Autophagy in Cadmium Nephrotoxicity
Toxics 2015, 3(2), 130-151; doi:10.3390/toxics3020130
Received: 15 March 2015 / Revised: 30 March 2015 / Accepted: 3 April 2015 / Published: 13 April 2015
Cited by 1 | PDF Full-text (1187 KB) | HTML Full-text | XML Full-text
Abstract
The transition metal ion cadmium (Cd2+) is a significant environmental contaminant. With a biological half-life of ~20 years, Cd2+ accumulates in the kidney cortex, where it particularly damages proximal tubule (PT) cells and can result in renal fibrosis, failure, [...] Read more.
The transition metal ion cadmium (Cd2+) is a significant environmental contaminant. With a biological half-life of ~20 years, Cd2+ accumulates in the kidney cortex, where it particularly damages proximal tubule (PT) cells and can result in renal fibrosis, failure, or cancer. Because death represents a powerful means by which cells avoid malignant transformation, it is crucial to clearly identify and understand the pathways that determine cell fate in chronic Cd2+ nephrotoxicity. When cells are subjected to stress, they make a decision to adapt and survive, or—depending on the magnitude and duration of stress—to die by several modes of death (programmed cell death), including autophagic cell death (ACD). Autophagy is part of a larger system of intracellular protein degradation and represents the channel by which organelles and long-lived proteins are delivered to the lysosome for degradation. Basal autophagy levels in all eukaryotic cells serve as a dynamic physiological recycling system, but they can also be induced by intra- or extracellular stress and pathological processes, such as endoplasmic reticulum (ER) stress. In a context-dependent manner, autophagy can either be protective and hence contribute to survival, or promote death by non-apoptotic or apoptotic pathways. So far, the role of autophagy in Cd2+-induced nephrotoxicity has remained unsettled due to contradictory results. In this review, we critically survey the current literature on autophagy in Cd2+-induced nephrotoxicity in light of our own ongoing studies. Data obtained in kidney cells illustrate a dual and complex function of autophagy in a stimulus- and time-dependent manner that possibly reflects distinct outcomes in vitro and in vivo. A better understanding of the context-specific regulation of cell fate by autophagy may ultimately contribute to the development of preventive and novel therapeutic strategies for acute and chronic Cd2+ nephrotoxicity. Full article
Open AccessReview Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms
Toxics 2015, 3(1), 20-62; doi:10.3390/toxics3010020
Received: 31 July 2014 / Revised: 4 September 2014 / Accepted: 14 January 2015 / Published: 26 January 2015
Cited by 5 | PDF Full-text (661 KB) | HTML Full-text | XML Full-text
Abstract
Mercury, cadmium, arsenic and lead are among priority metals for toxicological studies due to the frequent human exposure and to the significant burden of disease following acute and chronic intoxication. Among their common characteristics is chemical affinity to proteins and non-protein thiols [...] Read more.
Mercury, cadmium, arsenic and lead are among priority metals for toxicological studies due to the frequent human exposure and to the significant burden of disease following acute and chronic intoxication. Among their common characteristics is chemical affinity to proteins and non-protein thiols and their ability to generate cellular oxidative stress by the best-known Fenton mechanism. Their health effects are however diverse: kidney and liver damage, cancer at specific sites, irreversible neurological damages with metal-specific features. Mechanisms for the induction of oxidative stress by interaction with the cell thiolome will be presented, based on literature evidence and of experimental findings. Full article

2014

Jump to: 2015

Open AccessReview Cd, Pb and Hg Biomonitoring in Fish of the Mediterranean Region and Risk Estimations on Fish Consumption
Toxics 2014, 2(3), 417-442; doi:10.3390/toxics2030417
Received: 3 March 2014 / Revised: 21 July 2014 / Accepted: 6 August 2014 / Published: 18 August 2014
Cited by 2 | PDF Full-text (823 KB) | HTML Full-text | XML Full-text
Abstract
Cadmium (Cd), lead (Pb) and mercury (Hg) are toxic metals with increasing interest due to their tendency to bioaccumulate in fish tissue which may pose a threat to human health via fish consumption. This review of the recent literature on Cd, Pb, [...] Read more.
Cadmium (Cd), lead (Pb) and mercury (Hg) are toxic metals with increasing interest due to their tendency to bioaccumulate in fish tissue which may pose a threat to human health via fish consumption. This review of the recent literature on Cd, Pb, Hg levels summarizes data of fish biomonitoring studies in the Mediterranean Sea in order to determine potential risks due to dietary intake of metals. The analytical methods applied are described, with Atomic Absorption Spectroscopy and Inductively Coupled Plasma Mass Spectroscopy being the most popular. Most of the literature reviewed is focused on the Eastern Mediterranean. Results from the studies indicate that metals mostly accumulate in liver, followed by muscle. Although there are few studies reporting metal levels in fish exceeding the maximum residue levels (MRLs), the bulk of the studies cite levels below the MRLs. The hazard index (HI) of fish consumption, namely the ratio of estimated weekly intake to provisional tolerable weekly intake (EWI/PTWI) was estimated for adult consumers and no risk emerged. The EWI/PTWI ratios of lead and mercury for Italy (0.14 and 0.22 respectively) represent the highest HI levels estimated. In view of maximizing the benefits while minimizing the risks of fish consumption, a more detailed fish-specific database on intakes for consumers is required and extended bimonitoring in as many regions as possible. Full article
Open AccessReview An Update and Review of Unconventional Metals Testing and Treatment
Toxics 2014, 2(3), 403-416; doi:10.3390/toxics2030403
Received: 20 May 2014 / Revised: 29 July 2014 / Accepted: 30 July 2014 / Published: 11 August 2014
PDF Full-text (503 KB) | HTML Full-text | XML Full-text
Abstract
Most patients who receive unconventional testing for metals do not have any remarkable exposure history and typically lack symptoms or objective findings compatible with classic heavy metal intoxication. Unconventional tests results are usually promoted by alternative practitioners as the basis for recommending, [...] Read more.
Most patients who receive unconventional testing for metals do not have any remarkable exposure history and typically lack symptoms or objective findings compatible with classic heavy metal intoxication. Unconventional tests results are usually promoted by alternative practitioners as the basis for recommending, promoting, and selling to the patient questionable and often inappropriate therapies/interventions supposedly aimed at “detoxification”. Most of these patients will have no evidence of overexposure to metals on the basis of a thorough history and will have levels of metals on conventional tests performed at reliable laboratories that are undetectable, within population background ranges or above population background, but well below levels associated with toxicity. Full article
Open AccessReview The Alchemist’s Approach to Metal Poisoning: Transforming the Metal Burden
Toxics 2014, 2(3), 364-376; doi:10.3390/toxics2030364
Received: 21 February 2014 / Revised: 30 May 2014 / Accepted: 18 June 2014 / Published: 25 June 2014
Cited by 1 | PDF Full-text (485 KB) | HTML Full-text | XML Full-text
Abstract
Metal poisoning is a global problem with humans being exposed to a wide range of metals in varying doses and varying time frames. Traditionally, treatment involves removal of the toxic source or chelation therapy. An intermediate approach is needed. This review outlines [...] Read more.
Metal poisoning is a global problem with humans being exposed to a wide range of metals in varying doses and varying time frames. Traditionally, treatment involves removal of the toxic source or chelation therapy. An intermediate approach is needed. This review outlines the argument for the use of essential metal supplementation as a strategy to induce metallothionein expression and displace the toxic metal from important biological systems, improving the metal burden of the patient. Specific recommendations are given for supplementation with calcium, zinc and vitamin E as a broad strategy to improve the status of those exposed to toxic metals. Full article
Open AccessReview Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration
Toxics 2014, 2(2), 327-345; doi:10.3390/toxics2020327
Received: 6 May 2014 / Revised: 4 June 2014 / Accepted: 5 June 2014 / Published: 18 June 2014
Cited by 4 | PDF Full-text (975 KB) | HTML Full-text | XML Full-text
Abstract
As a cofactor of proteins and enzymes involved in critical molecular pathways in mammals and low eukaryotes, copper is a transition metal essential for life. The intra-cellular and extra-cellular metabolism of copper is under tight control, in order to maintain free copper [...] Read more.
As a cofactor of proteins and enzymes involved in critical molecular pathways in mammals and low eukaryotes, copper is a transition metal essential for life. The intra-cellular and extra-cellular metabolism of copper is under tight control, in order to maintain free copper concentrations at very low levels. Copper is a critical element for major neuronal functions, and the central nervous system is a major target of disorders of copper metabolism. Both the accumulation of copper and copper deficiency are associated with brain dysfunction. The redox capacities of free copper, its ability to trigger the production of reactive oxygen species and the close relationships with the regulation of iron and zinc are remarkable features. Major advances in our understanding of the relationships between copper, neuronal functions and neurodegeneration have occurred these last two decades. The metabolism of copper and the current knowledge on the consequences of copper dysregulation on brain disorders are reviewed, with a focus on neurodegenerative diseases, such as Wilson’s disease, Alzheimer’s disease and Parkinson’s disease. In vitro studies, in vivo experiments and evidence from clinical observations of the neurotoxic effects of copper provide the basis for future therapies targeting copper homeostasis. Full article
Open AccessArticle Effects of Lead and Cadmium on Brain Endothelial Cell Survival, Monolayer Permeability, and Crucial Oxidative Stress Markers in an in Vitro Model of the Blood-Brain Barrier
Toxics 2014, 2(2), 258-275; doi:10.3390/toxics2020258
Received: 2 April 2014 / Revised: 26 May 2014 / Accepted: 29 May 2014 / Published: 5 June 2014
Cited by 4 | PDF Full-text (706 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress, which is the loss of balance between antioxidant defense and oxidant production in the cells, is implicated in the molecular mechanism of heavy metal-induced neurotoxicity. Given the key role of lead (Pb) and cadmium (Cd) in inducing oxidative stress, we [...] Read more.
Oxidative stress, which is the loss of balance between antioxidant defense and oxidant production in the cells, is implicated in the molecular mechanism of heavy metal-induced neurotoxicity. Given the key role of lead (Pb) and cadmium (Cd) in inducing oxidative stress, we investigated their role in disrupting the integrity and function of immortalized human brain microvascular endothelial cells (hCMEC/D3). To study this, hCMEC/D3 cells were exposed to control media or to media containing different concentrations of Pb or Cd. Those exposed to Pb or Cd showed significantly higher oxidative stress than the untreated group, as indicated by cell viability, reactive oxygen species (ROS), glutathione (GSH) levels, and catalase enzyme activity. Pb also induced oxidative stress-related disruption of the hCMEC/D3 cell monolayer, as measured by trans-endothelial electrical resistance (TEER), the dextran permeability assay, and the level of tight junction protein, zona occluden protein (ZO-2). However, no significant disruption in the integrity of the endothelial monolayer was seen with cadmium at the concentrations used. Taken together, these results show that Pb and Cd induce cell death and dysfunction in hCMEC/D3 cells and, in the case of Pb, barrier disruption. This suggests blood brain barrier (BBB) dysfunction as a contributing mechanism in Pb and Cd neurotoxicities. Full article
Open AccessReview The Chemistry and Toxicology of Depleted Uranium
Toxics 2014, 2(1), 50-78; doi:10.3390/toxics2010050
Received: 14 January 2014 / Revised: 10 February 2014 / Accepted: 20 February 2014 / Published: 17 March 2014
Cited by 6 | PDF Full-text (877 KB) | HTML Full-text | XML Full-text
Abstract
Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU) is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ [...] Read more.
Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU) is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U) down to reactor grade uranium (~5% 235U), and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment. Full article

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