Toxics

2022

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12 pages, 1158 KiB

Open AccessArticle

Biochemical and Hematological Markers in Workers with Chronical Exposure to Lead and Cadmium in Colombia

by Fredy Vergara-Murillo, Katiana Martinez-Yanez, Alvaro Fortich-Revollo, Angel Paternina-Caicedo and Boris Johnson-Restrepo

Toxics 2022, 10(9), 524; https://doi.org/10.3390/toxics10090524 - 1 Sep 2022

Cited by 3 | Viewed by 2273

Abstract

The aim of the present study was to find if workers chronically exposed to lead (Pb) and cadmium (Cd) presented changes in their general health and in the clinical parameters of the population under study. We carried out a cross-sectional survey in a [...] Read more.

The aim of the present study was to find if workers chronically exposed to lead (Pb) and cadmium (Cd) presented changes in their general health and in the clinical parameters of the population under study. We carried out a cross-sectional survey in a sample of informal workers in Cartagena, Colombia. The population under study was composed of male informal workers (≥18 years of age), with experience in their job, selected from occupational settings with potential exposure to Pb and Cd (i.e., mechanics, battery and garbage recyclers, and welders). The median age was 45 years (interquartile range (IQR), 33–53). The median blood Pb level (BLL) was 2 μg/dL (IQR, 0.76–6.22), and the median of blood Cd level (BCL) was 1.22 μg/L (IQR, 0.33–2.01). The study found that 33% of high exposure jobs with BLL > 5 μg/dL (n = 57), whereas in ‘control’ workers, this was 15.3% (n = 9). The highest BLLs were found in battery recyclers (82.1%; n = 23), followed by mechanics (37.3%, n = 22). In the logistic regression model adjusted by age, time on the job, smoking and elevated BCL and BLL increased 3.2 times (95% CI, 1.1–9.7) in mechanics and 29.6 times (95% CI, 7.2–145.6) in battery recyclers. This study found negative changes in the health of workers with higher chronic exposure to lead in Cartagena, Colombia. Full article

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17 pages, 2585 KiB

Open AccessArticle

The Binding Ability of Mercury (Hg) to Photosystem I and II Explained the Difference in Its Toxicity on the Two Photosystems of Chlorella pyrenoidosa

by Shuzhi Wang, Jia Duo, Rehemanjiang Wufuer, Wenfeng Li and Xiangliang Pan

Toxics 2022, 10(8), 455; https://doi.org/10.3390/toxics10080455 - 6 Aug 2022

Cited by 7 | Viewed by 2285

Abstract

Mercury (Hg) poses high toxicity to organisms including algae. Studies showed that the growth and photosynthesis of green algae such as Chlorella are vulnerable to Hg stress. However, the differences between the activities and tolerance of photosystem I and II (PSI and PSII) [...] Read more.

Mercury (Hg) poses high toxicity to organisms including algae. Studies showed that the growth and photosynthesis of green algae such as Chlorella are vulnerable to Hg stress. However, the differences between the activities and tolerance of photosystem I and II (PSI and PSII) of green microalgae under Hg exposure are still little known. Responses of quantum yields and electron transport rates (ETRs) of PSI and PSII of Chlorella pyrenoidosa to 0.05–1 mg/L Hg²⁺ were simultaneously measured for the first time by using the Dual-PAM-100 system. The photosystems were isolated to analyze the characteristics of toxicity of Hg during the binding process. The inhibition of Hg²⁺ on growth and photosystems was found. PSII was more seriously affected by Hg²⁺ than PSI. After Hg²⁺ exposure, the photochemical quantum yield of PSII [Y(II)] decreased with the increase in non-photochemical fluorescence quenching [Y(NO) and Y(NPQ)]. The toxic effects of Hg on the photochemical quantum yield and ETR in PSI were lower than those of PSII. The stimulation of cyclic electron yield (CEF) was essential for the stability and protection of PSI under Hg stress and played an important role in the induction of non-photochemical quenching (NPQ). The results showed a strong combination ability of Hg ions and photosystem particles. The number of the binding sites (n) of Hg on PSII was more than that of PSI, which may explain the different toxicity of Hg on PSII and PSI. Full article

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17 pages, 2687 KiB

Open AccessArticle

Cadmium Caused Different Toxicity to Photosystem I and Photosystem II of Freshwater Unicellular Algae Chlorella pyrenoidosa (Chlorophyta)

by Shuzhi Wang, Rehemanjiang Wufuer, Jia Duo, Wenfeng Li and Xiangliang Pan

Toxics 2022, 10(7), 352; https://doi.org/10.3390/toxics10070352 - 28 Jun 2022

Cited by 13 | Viewed by 2399

Abstract

Heavy metals such as Cd pose environmental problems and threats to a variety of organisms. The effects of cadmium (Cd) on the growth and activities of photosystem I (PSI) and photosystem II (PSII) of Chlorella pyrenoidosa were studied. The growth rate of [...] Read more.

Heavy metals such as Cd pose environmental problems and threats to a variety of organisms. The effects of cadmium (Cd) on the growth and activities of photosystem I (PSI) and photosystem II (PSII) of Chlorella pyrenoidosa were studied. The growth rate of cells treated with 25 and 100 µM of Cd for longer than 48 h were significantly lower than the control, accompanying with the inhibition of photosynthesis. The result of quantum yields and electron transport rates (ETRs) in PSI and PSII showed that Cd had a more serious inhibition on PSII than on PSI. Cd decreased the efficiency of PSII to use the energy under high light with increasing Cd concentration. In contrast, the quantum yield of PSI did not show a significant difference among different Cd treatments. The activation of cyclic electron flow (CEF) and the inhibition of linear electron flow (LEF) due to Cd treatment were observed. The photochemical quantum yield of PSI and the tolerance of ETR of PSI to Cd treatments were due to the activation of CEF around PSI. The activation of CEF also played an important role in induction of non-photochemical quenching (NPQ). The binding features of Cd ions and photosystem particles showed that Cd was easier to combine with PSII than PSI, which may explain the different toxicity of Cd on PSII and PSI. Full article

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2018

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13 pages, 254 KiB

Open AccessReview

Diabetes and Exposure to Environmental Lead (Pb)

by Todd Leff, Paul Stemmer, Jannifer Tyrrell and Ruta Jog

Toxics 2018, 6(3), 54; https://doi.org/10.3390/toxics6030054 - 6 Sep 2018

Cited by 60 | Viewed by 6298

Abstract

Although the increased incidence of type 2 diabetes since the 1950s is thought to be primarily due to coincident alterations in lifestyle factors, another potential contributing factor in industrialized countries is exposure of the population to environmental pollutants and industrial chemicals. Exposure levels [...] Read more.

Although the increased incidence of type 2 diabetes since the 1950s is thought to be primarily due to coincident alterations in lifestyle factors, another potential contributing factor in industrialized countries is exposure of the population to environmental pollutants and industrial chemicals. Exposure levels of many environmental toxicants have risen in the same time-frame as the disease incidence. Of particular interest in this regard is the metal lead. Although overall lead exposure levels have diminished in recent decades, there is an under-recognized but persistent occurrence of lead exposure in poor underserved urban populations. Although the neural developmental pathologies induced by lead exposures have been well documented, very little is known about the effect of lead exposure on the incidence of chronic metabolic diseases such as type 2 diabetes. Although our understanding of the metabolic health effects of lead exposure is incomplete, there are studies in model systems and a small amount of epidemiological data that together suggest a deleterious effect of environmental lead exposure on metabolic health. This article reviews the human, animal and in vitro studies that have examined the effects of lead exposure on the development of diabetes and related metabolic conditions. Full article

10 pages, 390 KiB

Open AccessArticle

Lead Exposure and Oxidative Stress—A Life Course Approach in U.S. Adults

by Emmanuel Obeng-Gyasi

Toxics 2018, 6(3), 42; https://doi.org/10.3390/toxics6030042 - 1 Aug 2018

Cited by 45 | Viewed by 7029

Abstract

Lead exposure and a marker of oxidative stress (gamma-glutamyl transferase—GGT), and their effects on life course variables (age, country of birth, education levels, gender, ethnicity, income, and occupation) were explored in this cross-sectional study of United States (U.S.) adults’ ≥ 20 years of [...] Read more.

Lead exposure and a marker of oxidative stress (gamma-glutamyl transferase—GGT), and their effects on life course variables (age, country of birth, education levels, gender, ethnicity, income, and occupation) were explored in this cross-sectional study of United States (U.S.) adults’ ≥ 20 years of age via the National Health and Nutrition Examination Survey (NHANES) 2007–2010 datasets. Country of birth, education levels, gender, ethnicity, income, and occupation showed significant differences depending on the degree of lead exposure, with higher levels of exposure resulting in worse outcomes. Age and GGT were significantly associated with lead exposure. More must be done to mitigate sources of lead exposure, to prevent it from altering the life course of at-risk populations. Full article

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11 pages, 973 KiB

Open AccessArticle

Estimated Dietary Intake of Trace Metals from Swordfish Consumption: A Human Health Problem

by Grazia Barone, Angela Dambrosio, Arianna Storelli, Rita Garofalo, Vito Pietro Busco and Maria Maddalena Storelli

Toxics 2018, 6(2), 22; https://doi.org/10.3390/toxics6020022 - 3 Apr 2018

Cited by 38 | Viewed by 5419

Abstract

Trace element (Hg, Pb, Cd, Zn, Cu, Ni, and Cr) occurrence was determined in the muscle tissue of swordfish collected in the Mediterranean Sea to assess whether the intakes complied with the recommended levels for essential metals and permissible levels for toxic elements. [...] Read more.

Trace element (Hg, Pb, Cd, Zn, Cu, Ni, and Cr) occurrence was determined in the muscle tissue of swordfish collected in the Mediterranean Sea to assess whether the intakes complied with the recommended levels for essential metals and permissible levels for toxic elements. Metals were analyzed by an atomic absorption spectrophotometer (Shimadzu AA 7000). The methodology of Target Hazard Quotient (THQ) was also evaluated. The ranking order of toxic metal concentration was Hg > Cd > Pb, while for essential elements the distribution pattern followed the sequence Zn > Cu > Ni > Cr. The Estimated Weekly Intakes (EWI) as well as THQ for Cd and Pb indicated that swordfish consumption did not pose a risk to human health, whereas the major concern was for Hg. Fish size-related changes in Hg concentrations resulted in high EWI and THQ values relative to larger fish consumption, implying a potential risk to human health. For consumer protection, catches of swordfish approximately above 44 kg should be avoided as these fish have a higher risk of containing toxic levels of Hg. Full article

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2017

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1550 KiB

Open AccessArticle

The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological Monitoring Urinary Speciation Analysis

by Elizabeth Leese, Malcolm Clench, Jackie Morton, Philip H.E. Gardiner and Vikki A. Carolan

Toxics 2017, 5(2), 12; https://doi.org/10.3390/toxics5020012 - 20 May 2017

Cited by 8 | Viewed by 6676

Abstract

This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive’s Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As³⁺; arsenate, As⁵⁺; monomethylarsonic [...] Read more.

This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive’s Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As³⁺; arsenate, As⁵⁺; monomethylarsonic acid, MMA⁵⁺; and dimethylarsinic acid, DMA⁵⁺). Micro liquid chromatography coupled to inductively coupled plasma mass spectrometry (µLC-ICP-MS) and electrospray time of flight tandem mass spectrometry (ESI-QqTOF-MS/MS) were used to identify the two arsenic peaks by comparison to several characterized arsenicals: arsenocholine, AC; trimethyl arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE; thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio-dimethylarsenoethanol, thio-DMAE. The results from both the ICP-MS and ESI-QqTOF-MS/MS investigations indicate that the unexpected arsenic species termed peak 1 was thio-DMA. While the unexpected arsenic species termed peak 2 has yet to be identified, this investigation shows that it was not AC, TMAO, DMAA, DMAE, thio-DMA, thio-DMAA or thio-DMAE. This study demonstrates the incidence of unexpected arsenic species in both routine and non-routine urine samples from both workers and hospital patients. Full article

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2086 KiB

Open AccessArticle

Current Mercury Exposure from Artisanal and Small-Scale Gold Mining in Bombana, Southeast Sulawesi, Indonesia—Future Significant Health Risks

by Basri, Masayuki Sakakibara and Koichiro Sera

Toxics 2017, 5(1), 7; https://doi.org/10.3390/toxics5010007 - 8 Feb 2017

Cited by 30 | Viewed by 8499

Abstract

The rapid expansion of the artisanal and small-scale gold mining (ASGM) industry in developing countries has marginalized the local communities in poverty, and resulted in occupational exposure to mercury via the gold extraction process. We investigated the mercury exposure of the mining workers [...] Read more.

The rapid expansion of the artisanal and small-scale gold mining (ASGM) industry in developing countries has marginalized the local communities in poverty, and resulted in occupational exposure to mercury via the gold extraction process. We investigated the mercury exposure of the mining workers lived inside and outside the mining area. Based on the occupations of the contributors, the hair samples were divided into three subgroups: directly exposed, indirectly exposed, and a control. A total of 81 hair samples were analyzed by particle-induced X-ray emission spectrometry. The median mercury concentration was highest in the hair from the directly exposed group (12.82 μg/g hair) (control group median: 4.8 μg/g hair, p < 0.05), and the concentrations in hair from 45 respondents exceeded the Human Biomonitoring I (HBM I) threshold limit. Mercury concentrations were also elevated in the hair from the indirectly exposed group (median 7.64 μg/g hair, p < 0.05), and concentrations in hair from 24 respondents exceeded the HBM I threshold limits. Exposure to mercury during ASGM presents health risks and is harmful for the miners; mercury is also at hazardous levels for people who live in the mining area but who are not engaged in mercury-based gold extraction. Full article

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2015

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1420 KiB

Open AccessArticle

The Role of the Component Metals in the Toxicity of Military-Grade Tungsten Alloy

by Christy A. Emond, Vernieda B. Vergara, Eric D. Lombardini, Steven R. Mog and John F. Kalinich

Toxics 2015, 3(4), 499-514; https://doi.org/10.3390/toxics3040499 - 8 Dec 2015

Cited by 14 | Viewed by 5526

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 shrapnel [...] 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

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792 KiB

Open AccessReview

Speciation in Metal Toxicity and Metal-Based Therapeutics

by Douglas M. Templeton

Toxics 2015, 3(2), 170-186; https://doi.org/10.3390/toxics3020170 - 28 Apr 2015

Cited by 32 | Viewed by 8308

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 elements, [...] 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

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1187 KiB

Open AccessReview

Live and Let Die: Roles of Autophagy in Cadmium Nephrotoxicity

by Frank Thévenod and Wing-Kee Lee

Toxics 2015, 3(2), 130-151; https://doi.org/10.3390/toxics3020130 - 13 Apr 2015

Cited by 29 | Viewed by 12467

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, or [...] 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

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661 KiB

Open AccessReview

Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms

by Federico Maria Rubino

Toxics 2015, 3(1), 20-62; https://doi.org/10.3390/toxics3010020 - 26 Jan 2015

Cited by 121 | Viewed by 20562

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 and [...] 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

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2014

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823 KiB

Open AccessReview

Cd, Pb and Hg Biomonitoring in Fish of the Mediterranean Region and Risk Estimations on Fish Consumption

by Elisavet A. Renieri, Athanasios K. Alegakis, Michalis Kiriakakis, Marco Vinceti, Eren Ozcagli, Martin F. Wilks and Aristidis M. Tsatsakis

Toxics 2014, 2(3), 417-442; https://doi.org/10.3390/toxics2030417 - 18 Aug 2014

Cited by 60 | Viewed by 9974

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, Hg [...] 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

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503 KiB

Open AccessReview

An Update and Review of Unconventional Metals Testing and Treatment

by Diana J. Felton, Stefanos N. Kales and Rose H. Goldman

Toxics 2014, 2(3), 403-416; https://doi.org/10.3390/toxics2030403 - 11 Aug 2014

Cited by 6 | Viewed by 12622

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, promoting, [...] 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

485 KiB

Open AccessReview

The Alchemist’s Approach to Metal Poisoning: Transforming the Metal Burden

by Wayne Briner

Toxics 2014, 2(3), 364-376; https://doi.org/10.3390/toxics2030364 - 25 Jun 2014

Cited by 6 | Viewed by 4831

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 the [...] 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

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Open AccessReview

Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

by Mario Manto

Toxics 2014, 2(2), 327-345; https://doi.org/10.3390/toxics2020327 - 18 Jun 2014

Cited by 97 | Viewed by 16607

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 concentrations [...] 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

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706 KiB

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

by Shakila Tobwala, Hsiu-Jen Wang, Joshua Warren Carey, William A. Banks and Nuran Ercal

Toxics 2014, 2(2), 258-275; https://doi.org/10.3390/toxics2020258 - 5 Jun 2014

Cited by 48 | Viewed by 12094

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 investigated [...] 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

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Open AccessReview

The Chemistry and Toxicology of Depleted Uranium

by Sidney A. Katz

Toxics 2014, 2(1), 50-78; https://doi.org/10.3390/toxics2010050 - 17 Mar 2014

Cited by 44 | Viewed by 13666

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 million [...] 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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