Arsenic intoxication: general aspects and chelating agents

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Abstract

Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator–metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents.

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Arsenic toxicity and potential mechanisms of action.

Michael Hughes (2002)

Exposure to the metalloid arsenic is a daily occurrence because of its environmental pervasiveness. Arsenic, which is found in several different chemical forms and oxidation states, causes acute and chronic adverse health effects, including cancer. The metabolism of arsenic has an important role in its toxicity. The metabolism involves reduction to a trivalent state and oxidative methylation to a pentavalent state. The trivalent arsenicals, including those methylated, have more potent toxic properties than the pentavalent arsenicals. The exact mechanism of the action of arsenic is not known, but several hypotheses have been proposed. At a biochemical level, inorganic arsenic in the pentavalent state may replace phosphate in several reactions. In the trivalent state, inorganic and organic (methylated) arsenic may react with critical thiols in proteins and inhibit their activity. Regarding cancer, potential mechanisms include genotoxicity, altered DNA methylation, oxidative stress, altered cell proliferation, co-carcinogenesis, and tumor promotion. A better understanding of the mechanism(s) of action of arsenic will make a more confident determination of the risks associated with exposure to this chemical.

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Arsenic round the world: a review.

Badal Kumar Mandal, Kazuo Suzuki (2002)

This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research studies are needed for improving arsenic risk assessment at low exposure levels urgently among all the arsenic research groups.

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Arsenic: toxicity, oxidative stress and human disease.

Z Jenisova, D Hudecova, K Jomova … (2011)

Arsenic (As) is a toxic metalloid element that is present in air, water and soil. Inorganic arsenic tends to be more toxic than organic arsenic. Examples of methylated organic arsenicals include monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. Reactive oxygen species (ROS)-mediated oxidative damage is a common denominator in arsenic pathogenesis. In addition, arsenic induces morphological changes in the integrity of mitochondria. Cascade mechanisms of free radical formation derived from the superoxide radical, combined with glutathione-depleting agents, increase the sensitivity of cells to arsenic toxicity. When both humans and animals are exposed to arsenic, they experience an increased formation of ROS/RNS, including peroxyl radicals (ROO•), the superoxide radical, singlet oxygen, hydroxyl radical (OH•) via the Fenton reaction, hydrogen peroxide, the dimethylarsenic radical, the dimethylarsenic peroxyl radical and/or oxidant-induced DNA damage. Arsenic induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. This review discusses aspects of chronic and acute exposures of arsenic in the etiology of cancer, cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease and renal disease, reproductive health effects, dermal changes and other health disorders. The role of antioxidant defence systems against arsenic toxicity is also discussed. Consideration is given to the role of vitamin C (ascorbic acid), vitamin E (α-tocopherol), curcumin, glutathione and antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in their protective roles against arsenic-induced oxidative stress. Copyright © 2011 John Wiley & Sons, Ltd.

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Author and article information

Contributors

Geir Bjørklund: bjorklund@conem.org

Massimiliano Peana: peana@uniss.it

Journal

Journal ID (nlm-ta): Arch Toxicol

Journal ID (iso-abbrev): Arch. Toxicol

Title: Archives of Toxicology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0340-5761

ISSN (Electronic): 1432-0738

Publication date (Electronic): 9 May 2020

Pages: 1-19

Affiliations

[1 ]Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610 Mo i Rana, Norway

[2 ]GRID grid.411517.7, ISNI 0000 0004 0563 0685, Danylo Halytsky Lviv National Medical University, ; Lviv, Ukraine

[3 ]GRID grid.411517.7, ISNI 0000 0004 0563 0685, CONEM Ukraine Life Science Research Group, , Danylo Halytsky Lviv National Medical University, ; Lviv, Ukraine

[4 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Graduate School of Environmental Science, , Hokkaido University, ; Sapporo, Japan

[5 ]GRID grid.77054.31, ISNI 0000 0001 1245 4606, Ivan Franko National University of Lviv, ; Lviv, Ukraine

[6 ]GRID grid.445562.4, ISNI 0000 0004 0478 8296, National University of Pharmacy, ; Kharkiv, Ukraine

[7 ]GRID grid.445562.4, ISNI 0000 0004 0478 8296, CONEM Ukraine Pharmacognosy and Natural Product Chemistry Research Group, , National University of Pharmacy, ; Kharkiv, Ukraine

[8 ]GRID grid.11450.31, ISNI 0000 0001 2097 9138, Department of Chemistry and Pharmacy, , University of Sassari, ; Via Vienna 2, 07100 Sassari, Italy

Article

Publisher ID: 2739

DOI: 10.1007/s00204-020-02739-w

PMC ID: 7210463

PubMed ID: 32388818

SO-VID: 4c71b329-95ba-408d-83c2-7529aab958ba

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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Arsenic intoxication: general aspects and chelating agents

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Research from Ukraine

Most cited references 167

Arsenic toxicity and potential mechanisms of action.

Arsenic round the world: a review.

Arsenic: toxicity, oxidative stress and human disease.

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