Linking molecular targets of Cd in the bloodstream to organ-based adverse health effects

Hill, Alexander; Gailer, Jürgen

doi:10.1016/j.jinorgbio.2020.111279

Cited by 19 publications

(21 citation statements)

References 128 publications

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“…The results obtained are consistent with the literature data. In case of violation of physiological levels of metals in tissues and organs, competition for chemical active groups and catalytic centers in macromolecules with changes in their structure and functions is possible [36,37]. On the other hand, changes in the level of macro- and microelements can be considered as an adaptive reaction - the body’s response to the intake of cadmium ions.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Changes in Cadmium Levels in Environmental Objects and its Impact on the Bio-Elemental Composition of Living Organisms

Nechytailo

Danyliv

Kuras

et al. 2023

Preprint

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As a result of intensive anthropogenic impact in the biosphere there is a rapid process of accumulation of heavy metal salts. They have led to the aggravation of problems associated with the pollution of ecosystems and basic food products of plant and animal origin. Environmental pollution by these compounds is caused by their persistence in environmental objects, migration ability, accumulation by plants. This contributes to their accumulation in the human environment. A number of studies have shown that heavy metals have mutagenic, toxic effects and affect the intensity of biochemical processes. Therefore, the presence of heavy metals in the environment is extremely undesirable. Moreover, the ecological state of the environment is directly related to changes in the human internal environment. Deficiency or excess of certain bioelements in soils and drinking water or non-compliance with its stable chemical composition causes the development of dysmicroelementosis. The ecological situation of the Carpathian region is closely related to the state of soils and water resources. In this regard, it is advisable to study and control the level of cadmium compounds in the environment of the region. The study of the effect of cadmium intoxication on the macro- and microelement composition of the brain and myocardium of experimental animals is also worthwhile. Materials and methods: Soils and drinking water of the plain, foothill and mountainous zones of the region, as well as organs and tissues of experimental animals served as the object of research. Cadmium levels in drinking water and myocardial tissues and brain of experimental animals have been measured by atomic absorption spectroscopy. Results and discussion: The study of soils in the Prykarpattia region has revealed an increase in the toxic element cadmium. Its content is 1.1-1.5 times higher than background levels. The analysis of drinking water allowed to establish that a significant number of people living in the plain and foothill zone of the region consume water with a high content of cadmium. The main stages of cadmium intake and accumulation in plants have been analyzed. Significant disorders in the body of experimental animals under conditions of excessive intake of cadmium compounds have been revealed. It was accompanied by the accumulation of cadmium in the myocardium and brain, on the background of redistribution of vital macronutrients calcium and magnesium along with micronutrients copper and zinc. Thus, excessive intake of cadmium salts causes the development of dysmicroelementosis, which is accompanied by a violation of the homeostasis of a living organism. It is suggested to conduct continuous monitoring of the level of toxicants in the ecosystem as an integral component of environmental monitoring.

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Section: Discussionmentioning

confidence: 99%

Dynamics of Changes in Cadmium Levels in Environmental Objects and its Impact on the Bio-Elemental Composition of Living Organisms

Nechytailo

Danyliv

Kuras

et al. 2023

Preprint

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“…Given the dynamic flow of inorganic and toxic elements through mammalian organisms and owing to the paucity of information on the mechanistic basis of environmental metal exposure and pregnancy outcomes [ 59 ] gaining insight into the environment–bloodstream–organ system [ 112 ] is critical. To this end, events that unfold in the bloodstream are of focal interest as they play an important role in determining the onset of organ damage [ 68 , 134 ] and may also be implicated in human diseases of unknown etiology [ 35 , 135 ]. Besides, blood plasma is also a valuable matrix to analyze tissue-specific markers and probably can be useful in screening for both exposure and effect markers in the same compartment simultaneously with the use of appropriate instrumental analysis methods.…”

Section: Discussionmentioning

confidence: 99%

“…Although this hCys concentration was higher than what is observed in hyperhomocysteinemia patients, the fact that the results were obtained under near physiological conditions provide a rationale to more systematically investigate the role that this metabolite may play in the translocation of this and other toxic metal species to target organs. Accordingly, an important research avenue is to connect the bioinorganic chemistry of toxic metal species in the bloodstream with uptake mechanisms on the surface of target organ cells and the biomolecular mechanisms of organ damage [ 35 , 108 ]. This strategy will require not only to determine the structure of the actual metal species that is uptaken into an organ [ 109 ], but also to obtain knowledge about their uptake into various organ cell types.…”

Section: Dynamic Interactions Between Toxic Metal Species Plasma Proteins and Smw Thiolsmentioning

confidence: 99%

“…Last but not least, we will discuss the important role that dynamic interactions between plasma proteins and small molecular weight (SMW) metabolites play in the disposition of toxic metal species to target organs. Systems toxicology will be identified as a useful approach to obtain deeper insight into how the chronic exposure of human populations to toxic metals is potentially linked to disease processes [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Toxic Metal Species and ‘Endogenous’ Metalloproteins at the Blood–Organ Interface: Analytical and Bioinorganic Aspects

2021

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Globally, human exposure to environmental pollutants causes an estimated 9 million deaths per year and it could also be implicated in the etiology of diseases that do not appear to have a genetic origin. Accordingly, there is a need to gain information about the biomolecular mechanisms that causally link exposure to inorganic environmental pollutants with distinct adverse health effects. Although the analysis of blood plasma and red blood cell (RBC) cytosol can provide important biochemical information about these mechanisms, the inherent complexity of these biological matrices can make this a difficult task. In this perspective, we will examine the use of metalloentities that are present in plasma and RBC cytosol as potential exposure biomarkers to assess human exposure to inorganic pollutants. Our primary objective is to explore the principal bioinorganic processes that contribute to increased or decreased metalloprotein concentrations in plasma and/or RBC cytosol. Furthermore, we will also identify metabolites which can form in the bloodstream and contain essential as well as toxic metals for use as exposure biomarkers. While the latter metal species represent useful biomarkers for short-term exposure, endogenous plasma metalloproteins represent indicators to assess the long-term exposure of an individual to inorganic pollutants. Based on these considerations, the quantification of metalloentities in blood plasma and/or RBC cytosol is identified as a feasible research avenue to better understand the adverse health effects that are associated with chronic exposure of various human populations to inorganic pollutants. Exposure to these pollutants will likely increase as a consequence of technological advances, including the fast-growing applications of metal-based engineering nanomaterials.

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“…Дефіцит Fe виникає через конкуренцію Cd з Fe за всмоктування в кишечнику [10]. Однак, разом з анемією часто спостерігається збільшення вмісту Fe в організмі у випадках парентерального впливу Cd або хвороби Ітай-Ітай, що може бути обумовлено збільшенням рівня Fe внаслідок гемолізу, недостатнього еритропоезу та надмірного виробництва феритину в печінці, спричиненого Cd-залежним інтерлейкіном-6 [32]. Ниркова анемія спостерігається на останній стадії хронічної, важкої інтоксикації Cd, такої як хвороба Ітай-Ітай [3].…”

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Multiple Effects of Chronic Low-Dose Cadmium Exposure on the Liver, Osteogenesis, and Hematopoiesis in Animals and Humans

Zemlianyi¹,

Gerasymchuk²,

Zaitsev³

et al. 2021

Ukr. ž. med. bìol. sportu

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Cadmium salts are among the TOP-20 of the most dangerous compounds for animals in terms of toxicity. At the same time, today there is a paradigm shift in the studies of cadmium effects: in contrast to the acute effects of intoxication, more importance and practical relevance is attained by studying the continued chronic exposure to small cadmium doses (Chronic Low Cd Exposure) which can take place in real environmental conditions of industrially polluted regions and already impacts about 10% of the world population. While the early changes in kidneys and marker parameters of the urinary system under the action of cadmium are being studied quite actively, cadmium effects on other organs and systems in the body are insufficiently investigated. The purpose of the study was to analyse the multiple effects of cadmium on liver function, osteogenesis, haematopoiesis, and haemostasis in animals and humans. Protective mechanisms that reduce cadmium accumulation in hepatocytes compared to renal cells, in particular, the role of cellular transporters of biogenic metal ions (Fe2+, Zn2+, Mn2+, Cu2+), are systematized. Results and discussion. Cadmium mostly uses divalent metal transporter 1 and Zrt/Irt-like transporters, such as ZIP8 and ZIP14. Given the role of liver in the chelation and deposition of cadmium in the form of complexes with metallothioneins and glutathione, the significant potential of chelating and antioxidant hepatoprotectants to reduce negative effects is suggested. The role of exogenous chemical chelators and antioxidants in detoxifying cadmium is supported by the studies of other cadmium-binding molecules (glutathione, polyphenols, anthocyanins). Both direct effects of cadmium on the osteogenesis and calcium metabolism, and indirect effects on osteoblasts and osteoclasts are considered. In particular, current data on cadmium role in the development of endemic disease Itai-Itai in Japan is discussed. Notably, cadmium effect in children has a special hazards and long-term consequences. Data on cadmium role in interfering Ca2+ metabolism, particularly its effects on epithelial calcium channels (TRPV5) and Na-phosphate co-transporters (SLC34A1) are summarized. Conclusion. Current data suggest that chronic effects of cadmium in ultra-low concentrations upon the osteogenesis are even more evident than in renal system. A review of current data on cadmium effects upon the hematopoietic system in animal models is presented. The earliest studies found relation between cadmium and haemoglobin decrease, which could be mediated by interfering with intracellular Fe traffic, and effects on erythropoietin synthesis. Cadmium affected haemostasis and increased platelet aggregation. Animal studies suggest that chronic cadmium toxicity leads to hypercoagulation and increases the risks of thrombosis. Based on the summarized data, it is concluded that the investigating cadmium effects on hematopoiesis and hemostasis is a promising area for further studies of chronic low-dose cadmium exposure

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Linking molecular targets of Cd in the bloodstream to organ-based adverse health effects

Cited by 19 publications

References 128 publications

Dynamics of Changes in Cadmium Levels in Environmental Objects and its Impact on the Bio-Elemental Composition of Living Organisms

Dynamics of Changes in Cadmium Levels in Environmental Objects and its Impact on the Bio-Elemental Composition of Living Organisms

Toxic Metal Species and ‘Endogenous’ Metalloproteins at the Blood–Organ Interface: Analytical and Bioinorganic Aspects

Multiple Effects of Chronic Low-Dose Cadmium Exposure on the Liver, Osteogenesis, and Hematopoiesis in Animals and Humans

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