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      The Effects of Cadmium Toxicity

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          Abstract

          Cadmium (Cd) is a toxic non-essential transition metal that poses a health risk for both humans and animals. It is naturally occurring in the environment as a pollutant that is derived from agricultural and industrial sources. Exposure to cadmium primarily occurs through the ingestion of contaminated food and water and, to a significant extent, through inhalation and cigarette smoking. Cadmium accumulates in plants and animals with a long half-life of about 25–30 years. Epidemiological data suggest that occupational and environmental cadmium exposure may be related to various types of cancer, including breast, lung, prostate, nasopharynx, pancreas, and kidney cancers. It has been also demonstrated that environmental cadmium may be a risk factor for osteoporosis. The liver and kidneys are extremely sensitive to cadmium’s toxic effects. This may be due to the ability of these tissues to synthesize metallothioneins (MT), which are Cd-inducible proteins that protect the cell by tightly binding the toxic cadmium ions. The oxidative stress induced by this xenobiotic may be one of the mechanisms responsible for several liver and kidney diseases. Mitochondria damage is highly plausible given that these organelles play a crucial role in the formation of ROS (reactive oxygen species) and are known to be among the key intracellular targets for cadmium. When mitochondria become dysfunctional after exposure to Cd, they produce less energy (ATP) and more ROS. Recent studies show that cadmium induces various epigenetic changes in mammalian cells, both in vivo and in vitro, causing pathogenic risks and the development of various types of cancers. The epigenetics present themselves as chemical modifications of DNA and histones that alter the chromatin without changing the sequence of the DNA nucleotide. DNA methyltransferase, histone acetyltransferase, histone deacetylase and histone methyltransferase, and micro RNA are involved in the epigenetic changes. Recently, investigations of the capability of sunflower ( Helianthus annuus L.), Indian mustard ( Brassica juncea), and river red gum ( Eucalyptus camaldulensis) to remove cadmium from polluted soil and water have been carried out. Moreover, nanoparticles of TiO 2 and Al 2O 3 have been used to efficiently remove cadmium from wastewater and soil. Finally, microbial fermentation has been studied as a promising method for removing cadmium from food. This review provides an update on the effects of Cd exposure on human health, focusing on the cellular and molecular alterations involved.

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          Current status of cadmium as an environmental health problem.

          Cadmium is a toxic metal occurring in the environment naturally and as a pollutant emanating from industrial and agricultural sources. Food is the main source of cadmium intake in the non-smoking population. The bioavailability, retention and toxicity are affected by several factors including nutritional status such as low iron status. Cadmium is efficiently retained in the kidney (half-time 10-30 years) and the concentration is proportional to that in urine (U-Cd). Cadmium is nephrotoxic, initially causing kidney tubular damage. Cadmium can also cause bone damage, either via a direct effect on bone tissue or indirectly as a result of renal dysfunction. After prolonged and/or high exposure the tubular injury may progress to glomerular damage with decreased glomerular filtration rate, and eventually to renal failure. Furthermore, recent data also suggest increased cancer risks and increased mortality in environmentally exposed populations. Dose-response assessment using a variety of early markers of kidney damage has identified U-Cd points of departure for early kidney effects between 0.5 and 3 microg Cd/g creatinine, similar to the points of departure for effects on bone. It can be anticipated that a considerable proportion of the non-smoking adult population has urinary cadmium concentrations of 0.5 microg/g creatinine or higher in non-exposed areas. For smokers this proportion is considerably higher. This implies no margin of safety between the point of departure and the exposure levels in the general population. Therefore, measures should be put in place to reduce exposure to a minimum, and the tolerably daily intake should be set in accordance with recent findings.
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            Cadmium stress: an oxidative challenge.

            At the cellular level, cadmium (Cd) induces both damaging and repair processes in which the cellular redox status plays a crucial role. Being not redox-active, Cd is unable to generate reactive oxygen species (ROS) directly, but Cd-induced oxidative stress is a common phenomenon observed in multiple studies. The current review gives an overview on Cd-induced ROS production and anti-oxidative defense in organisms under different Cd regimes. Moreover, the Cd-induced oxidative challenge is discussed with a focus on damage and signaling as downstream responses. Gathering these data, it was clear that oxidative stress related responses are affected during Cd stress, but the apparent discrepancies observed in between the different studies points towards the necessity to increase our knowledge on the spatial and temporal ROS signature under Cd stress. This information is essential in order to reveal the exact role of Cd-induced oxidative stress in the modulation of downstream responses under a diverse array of conditions.
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              Nickel: Human Health and Environmental Toxicology

              Nickel is a transition element extensively distributed in the environment, air, water, and soil. It may derive from natural sources and anthropogenic activity. Although nickel is ubiquitous in the environment, its functional role as a trace element for animals and human beings has not been yet recognized. Environmental pollution from nickel may be due to industry, the use of liquid and solid fuels, as well as municipal and industrial waste. Nickel contact can cause a variety of side effects on human health, such as allergy, cardiovascular and kidney diseases, lung fibrosis, lung and nasal cancer. Although the molecular mechanisms of nickel-induced toxicity are not yet clear, mitochondrial dysfunctions and oxidative stress are thought to have a primary and crucial role in the toxicity of this metal. Recently, researchers, trying to characterize the capability of nickel to induce cancer, have found out that epigenetic alterations induced by nickel exposure can perturb the genome. The purpose of this review is to describe the chemical features of nickel in human beings and the mechanisms of its toxicity. Furthermore, the attention is focused on strategies to remove nickel from the environment, such as phytoremediation and phytomining.
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                Author and article information

                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                26 May 2020
                June 2020
                : 17
                : 11
                : 3782
                Affiliations
                [1 ]Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria, 87036 Arcavacata di Rende (Cosenza), Italy; giuseppe.genchi@ 123456unical.it (G.G.); glauria@ 123456unical.it (G.L.)
                [2 ]Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “A. Moro”, 70125 Bari, Italy; alessia.catalano@ 123456uniba.it
                Author notes
                [* ]Correspondence: s.sinicropi@ 123456unical.it (M.S.S.); alessia.carocci@ 123456uniba.it (A.C.); Tel.: +39-0984493200 (M.S.S.); +39-0805442731 (A.C.)
                Author information
                https://orcid.org/0000-0003-0538-4907
                https://orcid.org/0000-0003-2435-8931
                https://orcid.org/0000-0003-2248-9292
                https://orcid.org/0000-0002-7420-4706
                Article
                ijerph-17-03782
                10.3390/ijerph17113782
                7312803
                32466586
                e0767459-e11d-4323-a7a7-fac337ea8ba4
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 May 2020
                : 23 May 2020
                Categories
                Review

                Public health
                antioxidant,apoptosis,cadmium,cancer,chelators,metallothioneins,phytoremediation,damage of mitochondria

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