Metal chelation therapy in rheumathoid arthritis: a case report

Toxic metals are involved in the pathogenesis of some neurodegenerative and vascular diseases and are known to impair the immune system functions. We report here the case of a patient affected by heavy metal intoxication, who had developed an autoimmune disease. There was evidence of aluminium, cadmium and lead intoxication in a 63-year old Italian woman affected by rheumatoid arthritis (RA). We treated the patient with calcium disodium edetate (EDTA) once a week for a year in order to remove traces of heavy metal intoxication. Oxidative status profile was carried out at the beginning and after 6 months’ EDTA chelation. At the end of the treatment, the patient did not show any signs of metal intoxication, RA symptoms and oxidative status improved.     

Heavy Metals and Neurodegenerative Diseases: An Observational Study

In this study, we evaluated the levels of some of the most investigated metals (Cu, Se, Zn, Pb, and Hg) in the blood of patients affected by the most common chronic neurodegenerative diseases like Alzheimer’s disease (AD) and multiple sclerosis (MS), in order to better clarify their involvement. For the first time, we investigated a Sicilian population living in an area exposed to a potentially contaminated environment from dust and fumes of volcano Etna and consumer of a considerable quantity of fish in their diet, so that this represents a good cohort to demonstrate a possible link between metals levels and development of neurodegenerative disorders. More specifically, 15 patients affected by AD, 41 patients affected by MS, 23 healthy controls, and 10 healthy elderly controls were recruited and subjected to a venous blood sampling. Quantification of heavy metals was performed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). This technique has allowed us to establish that there is a concomitance of heavy metal unbalance associated with AD more than in other neurodegenerative pathologies, such as MS. Also, we can assess that the concentration of these elements is independent from the diet, especially from occasional or habitual consumption of fruits and vegetables, prevalence in the diet of meat or fish, possible exposure to contaminated environment due both to the occupation and place of residence.     

Determination by ICP-MS and multivariate data analysis of elemental urine excretion profile during the EDTA chelation therapy: A case study

BackgroundBased on the medical history and laboratory analytical tests, a patient presenting symptoms compatible with Chronic Fatigue Syndrome was suspected of metal intoxication; therefore, a chelating therapy was attempted. In parallel, the profile of elemental excretion in urine was determined.MethodsChelation therapy by CaNa₂EDTA was administered every two weeks and urine samples were routinely collected for 17 months. The samples were mineralized with HNO₃ 69 % and analyzed by Inductively-Coupled Plasma – Mass Spectrometry. Data were processed by multivariate statistical methods.ResultsMost of the toxic elements showed a peak of excretion in 12−24 h after EDTA administration, which returned to basal level by 24−36 h after the treatment. Yet, the excretion of some trace elements persisted in the urine collected 26 h after the treatment.ConclusionsThe analysis of excreted metals following the CaNa₂EDTA infusion allowed to monitor dynamically the chelation therapy. The chelation therapy was effective in mobilizing and eliminating the principal heavy metals present from the body. However, since such clearance almost vanished 24 h after the treatment, a protocol with more frequent and low-dose administrations is advisable to improve the metal excretion.     

PHYCOLOGY AND HEAVY-METAL POLLUTION

1. All heavy metals, including those that are essential micronutrients (e.g. copper, zinc, etc.), are toxic to algae at high concentrations. 2. One characteristic feature of heavy-metal toxicity is the poisoning and inactivation of enzyme systems. Many of the physiological and biochemical processes, viz., photosynthesis, respiration, protein synthesis and chlorophyll synthesis, etc., are severely affected at high metal concentrations. 3. Some algae inhabit waters chronically polluted with heavy-metal-laden wastes from mining and smelting operations; Nodularia sp., Oscillatoria sp., Cladophora sp., Hormidium sp., Fucus sp. and Laminaria sp., etc., occur in metal-rich waters. These algal forms are probably more capable of combating the toxic levels of heavy metals and this attribute is a result of physiological and/or genetic adaptations. The sensitivity or tolerance to heavy metals varies amongst different algae. The phenomena of multiple tolerance and co-tolerance may be exhibited by some algae. 4. Heavy-metal pollution causes reduction in species diversity leading to the dominance of a few tolerant algal forms. The primary productivity also decreases after metal supplementation. 5. The uptake and accumulation of heavy metals can be active (energy-dependent), passive (energy-independent), or both. 6. Heavy metals can be safely stored as intranuclear complexes by some algae. Notwithstanding this, some changes in the cell wall can enable the algae to tolerate heavy metals by checking the entry of the metals (exclusion mechanism). 7. The metal content of algae growing in a waterbody may yield valuable information for simulating heavy metal pollution: several species of Cladophora and Fucus have been extensively used for this purpose. 8. Several factors affect and determine toxicity of heavy metals to algae. At low pH, the availability of heavy metals to algae is greatly increased, as a consequence of which pronounced toxicity is evident. Hard waters decrease metal toxicity. Some ions, e.g., calcium, magnesium and phosphorus, can alleviate toxicity of metals. 9. The presence of other metals can influence toxicity of a heavy metal through simple additive effect or by synergistic and antagonistic interactions. Similarly, other pollutants can influence heavy-metal toxicity. 10. The toxicity of heavy metals depends upon their chemical speciation. Various ionic forms of a metal characterized by different valency states, may be differentially toxic to a test alga. 11. Amino acids, organic matter, humic acids, fulvic acid, EDTA, NTA, etc. can complex with heavy metals and render them unavailable. This may eventually lead to less toxicity. 12. Heavy-metal toxicity largely depends upon algal population density: the denser the population the more numerous the cellular sites available, leading to decreased toxicity.     

Enhanced phytoextraction: I. Effect of EDTA and citric acid on heavy metal mobility in a calcareous soil

Phytoextraction, the use of plants to extract heavy metals from contaminated soils, could be an interesting alternative to conventional remediation technologies. However, calcareous soils with relatively high total metal contents are difficult to phytoremediate due to low soluble metal concentrations. Soil amendments such as ethylene diaminetetraacetate (EDTA) have been suggested to increase heavy metal bioavailability and uptake in aboveground plant parts. Strong persistence of EDTA and risks of leaching of potentially toxic metals and essential nutrients have led to research on easily biodegradable soil amendments such as citric acid. In our research, EDTA is regarded as a scientific benchmark with which degradable alternatives are compared for enhanced phytoextraction purposes. The effects of increasing doses of EDTA (0.1,1,10 mmol kg(-1) dry soil) and citric acid (0.01, 0.05, 0.25, 0.442, 0.5 mol kg(-1) dry soil) on bioavailable fractions of Cu, Zn, Cd, and Pb were assessed in one part of our study and results are presented in this article. The evolution of labile soil fractions of heavy metals over time was evaluated using water paste saturation extraction (approximately soluble fraction), extraction with 1 M NH4OAc at pH 7 (approximately exchangeable fraction), and extraction with 0.5 M NH4OAc + 05 M HOAc + 0.02 M EDTA at pH 4.65 (approximately potentially bioavailable fraction). Both citric acid and EDTA produced a rapid initial increase in labile heavy metal fractions. Metal mobilization remained constant in time for soils treated with EDTA, but a strong exponential decrease of labile metal fractions was noted for soils treated with citric acid. The half life of heavy metal mobilization by citric acid varied between 1.5 and 5.7 d. In the following article, the effect of heavy metal mobilization on uptake by Helianthus annuus will be presented.     

Metalloproteomics and metal toxicology of α-synuclein

Significant evidence has been accumulated linking exposure to heavy metals and/or distortion of metal homeostasis with the development of various neurodegenerative diseases. α-Synuclein is known to be involved in pathogenesis of a subset of neurodegenerative diseases collectively known as synucleinopathies. Therefore the interplay between metals, α-synuclein and neurodegeneration has attracted significant attention of researchers. This review discusses some of the aspects of the α-synuclein metalloproteomics and represents the peculiarities and consequences of α-synuclein interaction with various metal ions. Both non-specific and specific binding of this protein to metals is considered together with the analysis of the effects of such interactions on α-synuclein structure and aggregation propensity.     

解磷微生物修复土壤重金属污染研究进展

土壤重金属污染问题日益严重,具有普遍性、隐蔽性、表聚性、不可逆性等特点,已经成为环境污染治理中的热点、难点问题。解磷微生物能够依靠自身的代谢产物或通过与其他生物的协同作用,将土壤中的难溶性磷转化为可供植物吸收利用的磷,具有多重植物促生长功能和重金属解毒能力,可在重金属毒害水平下,促进植物生长、提高植物抗病能力、克服重金属对植物生长的不利影响,从而增强重金属修复植物的生存竞争力。从解磷微生物的研究现状入手,介绍了解磷微生物对土壤重金属污染的修复能力,综述了解磷微生物对土壤重金属污染修复的作用机制,分析了目前解磷微生物在重金属修复过程中存在的问题,并提出了今后研究的方向,为重金属污染土壤的修复提供了新思路。     

Biochemical changes and adaptive strategies of plants under heavy metal stress

Heavy metal contamination of soil, aqueous waste stream and ground water causes major environmental and human health problems. Heavy metals are major environmental pollutants when they are present in high concentration in soil and show potential toxic effects on growth and development in plants. Due to unabated, indiscriminate and uncontrolled discharge of hazardous chemicals including heavy metals into the environment, plant continuously have to face various environmental constraints. In plants, seed germination is the first exchange interface with the surrounding medium and has been considered as highly sensitive to environmental changes. One of the crucial events during seed germination entails mobilization of seed reserves which is indispensable for the growth of embryonic axis. But, metabolic alterations by heavy metal exposure are known to depress the mobilization and utilization of reserve food by affecting the activity of hydrolytic enzymes. Some plants possess a range of potential mechanisms that may be involved in the detoxification of heavy metals by which they manage to survive under metal stress. High tolerance to heavy metal toxicity could rely either on reduced uptake or increase planned internal sequestration which is manifested by an interaction between a genotype and its environment. Such mechanism involves the binding of heavy metals to cell wall, immobilization, exclusion of the plasma membrane, efflux of these toxic metal ions, reduction of heavy metal transport, compartmentalization and metal chelation by tonoplast located transporters and expression of more general stress response mechanisms such as stress proteins. It is important to understand the toxicity response of plant to heavy metals so that we can utilize appropriate plant species in the rehabilitation of contaminated areas. Therefore, in the present review attempts have been made to evaluate the effects of increasing level of heavy metal in soils on the key behavior of hydrolytic and nitrogen assimilation enzymes. Additionally, it also provides a broad overview of the strategies adopted by plants against heavy metal stress.     

EDTA-Enhanced Phytoremediation of Heavy Metals: A Review

The increase in heavy metal terrestrial ecosystems’ contamination through anthropogenic activities is a widespread and serious global problem due to their various environmental and human implications. For these reasons, several techniques, including phytoremediation of heavy metals, have been extensively studied. In spite of significant recent advancement, ethylene diamine tetraacetic acid (EDTA)-enhanced heavy metal phytoextraction as well as related ecological risks are still topical and remain an important area of research. In fact, EDTA favors the solubilization of metals and metalloids in soils, and was therefore extensively studied during the last two decades in order to improve phytoextraction efficiency and reduce treatment duration. This review highlights the recent findings (2010–2012) and mechanisms behind EDTA-enhanced (1) solubilization of heavy metals in soil, (2) mobilization/transport of soluble metals towards plant root zone, and (3) metal absorption by plant roots and translocation towards aerial parts. The review also presents potential risks associated with EDTA-enhanced phytoextraction: (1) environmental persistence of EDTA and/or metal-EDTA complex; (2) potential toxicity of EDTA and/or metal-EDTA complex to plants; and (3) leaching and contamination of groundwater. Moreover, field-scale cost of EDTA-enhanced remediation and the role of EDTA in time required for heavy metal remediation is discussed.     

植物重金属转运蛋白研究进展

土壤中的有毒重金属不仅对植物有害,也可通过食物链危害人类和动物的健康.重金属转运蛋白在植物吸收、抵抗重金属的复杂机制中起着关键作用.植物重金属转运蛋白分为吸收蛋白和排出蛋白,其中,吸收蛋白转运必需重金属进入细胞,同时也会因为必需重金属的缺乏或离子之间的竞争而运载有毒重金属;排出蛋白是一类解毒蛋白,可将过量的或有毒的重金属逆向转运出细胞,或区室化于液泡中.目前,细胞内多种重金属转运蛋白基因的转录水平与重金属离子积累之间的联系已被揭示,并分离克隆出诸多相关蛋白家族成员.本文综述了近年来发现并鉴定的主要重金属转运蛋白的金属亲和性、器官表达特异性及细胞内定位等的研究进展.     

The neurotoxicity of iron,copper and cobalt in Parkinson’s disease through ROS-mediated mechanisms

Parkinson’s disease (PD) is the second most common neurodegenerative disease with gradual loss of dopaminergic neurons. Despite extensive research in the past decades, the etiology of PD remains elusive. Nevertheless, multiple lines of evidence suggest that oxidative stress is one of the common causes in the pathogenesis of PD. It has also been suggested that heavy metal-associated oxidative stress may be implicated in the etiology and pathogenesis of PD. Here we review the roles of redox metals, including iron, copper and cobalt, in PD. Iron is a highly reactive element and deregulation of iron homeostasis is accompanied by concomitant oxidation processes in PD. Copper is a key metal in cell division process, and it has been shown to have an important role in neurodegenerative diseases such as PD. Cobalt induces the generation of reactive oxygen species (ROS) and DNA damage in brain tissues.     

Performance of rose scented geranium (Pelargonium graveolens) in heavy metal polluted soil vis-à-vis phytoaccumulation of metals

An investigation was carried out to evaluate the effect of heavy metal toxicity on growth, herb, oil yield and quality and metal accumulation in rose scented geranium (Pelargonium graveolens) grown in heavy metal enriched soils. Four heavy metals (Cd, Ni, Cr, and Pb) each at two levels (10 and 20 mg kg–1 soil) were tested on geranium. Results indicated that Cr concentration in soil at 20 mg kg–1 reduced leaves, stem and root yield by 70, 83, and 45%, respectively, over control. Root growth was significantly affected in Cr stressed soil. Nickel, Cr, and Cd concentration and accumulation in plant increased with higher application of these metals. Chromium, nickel and cadmium uptake was observed to be higher in leaves than in stem and roots. Essential oil constituents were generally not significantly affected by heavy metals except Pb at 10 and 20 ppm, which significantly increased the content of citronellol and Ni at 20 ppm increased the content of geraniol. Looking in to the higher accumulation of toxic metals by geranium and the minimal impact of heavy metals on quality of essential oil, geranium can be commercially cultivated in heavy metal polluted soil for production of high value essential oil.     

Enhanced phytoextraction: II. Effect of EDTA and citric acid on heavy metal uptake by Helianthus annuus from a calcareous soil

High biomass producing plant species, such as Helianthus annuus, have potential for removing large amounts of trace metals by harvesting the aboveground biomass if sufficient metal concentrations in their biomass can be achieved However, the low bioavailability of heavy metals in soils and the limited translocation of heavy metals to the shoots by most high biomass producing plant species limit the efficiency of the phytoextraction process. Amendment of a contaminated soil with ethylene diamine tetraacetic acid (EDTA) or citric acid increases soluble heavy metal concentrations, potentially rendering them more available for plant uptake. This article discusses the effects of EDTA and citric acid on the uptake of heavy metals and translocation to aboveground harvestable plant parts in Helianthus annuus. EDTA was included in the research for comparison purposes in our quest for less persistent alternatives, suitable for enhanced phytoextraction. Plants were grown in a calcareous soil moderately contaminated with Cu, Pb, Zn, and Cd and treated with increasing concentrations of EDTA (0.1, 1, 3, 5, 7, and 10 mmol kg(-1) soil) or citric acid (0.01, 0.05, 0.25, 0.442, and 0.5 mol kg(-1) soil). Heavy metal concentrations in harvested shoots increased with EDTA concentration but the actual amount of phytoextracted heavy metals decreased at high EDTA concentrations, due to severe growth depression. Helianthus annuus suffered heavy metal stress due to the significantly increased bioavailable metal fraction in the soil. The rapid mineralization of citric acid and the high buffering capacity of the soil made citric acid inefficient in increasing the phytoextracted amounts of heavy metals. Treatments that did not exceed the buffering capacity of the soil (< 0.442 mol kg(-1) soil) did not result in any significant increase in shoot heavy metal concentrations. Treatments with high concentrations resulted in a dissolution of the carbonates and compaction of the soil. These physicochemical changes caused growth depression of Helianthus annuus. EDTA and citric acid added before sowing of Helianthus annuus did not appear to be efficient amendments when phytoextraction of heavy metals from calcareous soils is considered.     

Heavy metals toxicity in plants: An overview on the role of glutathione and phytochelatins in heavy metal stress tolerance of plants

Plants experience oxidative stress upon exposure to heavy metals that leads to cellular damage. In addition, plants accumulate metal ions that disturb cellular ionic homeostasis. To minimize the detrimental effects of heavy metal exposure and their accumulation, plants have evolved detoxification mechanisms. Such mechanisms are mainly based on chelation and subcellular compartmentalization. Chelation of heavy metals is a ubiquitous detoxification strategy described in wide variety of plants. A principal class of heavy metal chelator known in plants is phytochelatins (PCs), a family of Cys-rich peptides. PCs are synthesized non-translationally from reduced glutathione (GSH) in a transpeptidation reaction catalyzed by the enzyme phytochelatin synthase (PCS). Therefore, availability of glutathione is very essential for PCs synthesis in plants at least during their exposure to heavy metals. Here, I reviewed on effect of heavy metals exposure to plants and role of GSH and PCs in heavy metal stress tolerance. Further, genetic manipulations of GSH and PCs levels that help plants to ameliorate toxic effects of heavy metals have been presented.     

Personal experiences of the psoriasis and its relation to the stressful life events

Psoriasis is a disease with a profound impact on the psychological and social aspects of the patient, particularly because of its visibility. Quality of life is impaired and different mental health disorders like depression, anxiety, alcoholism, posttraumatic stress disorder (PTSD) are found among persons suffering from psoriasis. Studies have shown the influence of stressful life events on onset, exacerbation and relapse of psoriasis. Rare studies explored prevalence of psoriasis during war times and relations between psoriasis and war provoked PTSD. Psoriasis is a disease with multiple possible causes and additional caution is necessary among medical professional to recognize all contributing factors. This report describes a case of a person whose first episode of psoriasis appeared six months after engaging in combat activities. He is diagnosed with psoriasis vulgaris, psoriatic arthritis and permanent personality changes after the traumatic experiences caused by war participation. His occupational history is burdened with additional causational factors; work with heavy metals and metal dusts. Cumulative effects of different aetiological factors can contribute to psoriasis with intensive trauma induced stressors serving as a trigger. His medical history indicates cognitive difficulties typical for early dementia which makes this case even more interesting. Research results suggesting common aetiology of psoriasis, autoimmune diseases and neurodegenerative diseases, indicate a need, as in the case of our patient, for multidisciplinary approach to studying aetiology of psoriasis.     

Effect of EDTA and Tannic Acid on the Removal of Cd,Ni, Pb and Cu from Artificially Contaminated Soil by Althaea rosea Cavan

In this study an ornamental plant of Althaea rosea Cavan was investigated for its potential use in the removal of Cd, Ni, Pb and Cu from an artificially contaminated soil. Effect of two different chelating agents on the removal has also been studied by using EDTA (ethylenediaminetetracetic acid) and TA (tannic acid). Both EDTA and TA have led to higher heavy metal concentration in shoots and leaves compared to control plants. However EDTA is generally known as an effective agent in metal solubilisation of soil, in this study, TA was found more effective to induce metal accumulation in Althaea rosea Cavan under the studied conditions. In addition to this, EDTA is toxic to some species and restraining the growth of the plants. The higher BCF (Bio Concentration Factor) and TF (Translocation Factor) values obtained from stems and leaves by the effects of the chemical enhancers (EDTA and TA) show that Althaea rosea Cavan is a hyper accumulator for the studied metals and may be cultivated to clean the contaminated soils.     

The role of trace elements on hepatitis virus infections: a review

The significance of the nutritional roles of trace metals (includes some heavy metals) is widely recognized, since these elements are as constituent components of many metal proteins and metalloenzymes serum trace metals levels, and their ratios are frequently reported to be good marker for diagnosing various diseases. Trace metals play an important role in liver disease particularly liver degeneration. Influence of trace elements has been studied in a large number of viruses belonging to different groups. This review reported the role of some trace elements iron (Fe), copper (Cu), cobalt (Co), manganese (Mn) and zinc (Zn) as well as toxic elements Pb on hepatitis virus infections.     

Recent developments in the application of proteomics to the analysis of plant responses to heavy metals

Pollution of soils by heavy metals is an ever‐growing problem throughout the world, and is the result of human activities as well as geochemical weathering of rocks and other environmental causes such as volcanic eruptions, acid rain and continental dusts. Plants everywhere are continuously exposed to metal‐contaminated soils. The uptake of heavy metals not only constrains crop yields, but can also be a major hazard to the health of humans and to the entire ecosystem. Although analysis of gene expression at the mRNA level has enhanced our understanding of the response of plants to heavy metals, many questions regarding the functional translated portions of plant genomes under metal stress remain unanswered. Proteomics offers a new platform for studying complex biological functions involving large numbers and networks of proteins, and can serve as a key tool for revealing the molecular mechanisms that are involved in interactions between toxic metals and plant species. This review focuses on recent developments in the applications of proteomics to the analysis of the responses of plants to heavy metals; such studies provide a deeper understanding of protein responses and the interactions among the possible pathways that are involved in detoxification of toxic metals in plant cells. In addition, the challenges faced by proteomics in understanding the responses of plants to toxic metal are discussed, and some possible future strategies for meeting these challenges are proposed.     

Twenty years of metallo-neurobiology: where to now?

The redox active transition metals Cu²⁺ and Fe³⁺ have been proposed as important factors in the neuropathology of Alzheimer’s disease (AD) and other neurodegenerative diseases. The field that has been called metallo-neurobiology has expanded greatly in the last 20 years. Although there is much experimental evidence on various aspects of the interaction between these metals and the molecular and supramolecular components of the neuropil and the structural biology of metal binding, we are far from fully understanding the part this interaction plays in the normal CNS and in neurodegeneration. This understanding is needed if we are to move beyond the promising, but semi-empirical, approaches to therapies of these diseases based on metal attenuation. Australian Society for Biophysics Special Issue: Metals and Membranes in Neurosciences.