Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects

Letelier, María Eugenia; Sánchez-Jofré, Sebastián; Peredo-Silva, Liliana; Cortés-Troncoso, Juan; Aracena-Parks, Paula

doi:10.1016/j.cbi.2010.06.013

Cited by 140 publications

(95 citation statements)

References 30 publications

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“…Cu induced ROS generation initiate apoptotic/necrotic processes or other pathologies like cancer, neurological diseases, and aging (14). It was found that, multiple sclerosis (MS) subjects had increased levels of Cu in their fluids or brain cells (15). The results of the present study showed that serum AST and ALT levels among workers were significantly higher than the office employees.…”

Section: Discussionsupporting

confidence: 53%

Hematological and hepatic alterations among copper mine workers and office employees in a copper mine in the west of Iran, 2015

Lotfi

Rezazadeh

Ebrahimpour

2018

JOHE

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Article InfoBackground: Workers in different occupational positions experience significant Cu exposures, however, Cu toxicity has not been fully studied as compared to other heavy metals. In the present study, hematological and hepatic alterations have been investigated among copper mine workers. Materials and Methods: This descriptive study was conducted in a copper mine in west of Iran, on 402 copper mine workers (study group) and 52 office employees (control group) during winter 2015. 5ml blood samples were provided from each subject and hematological and hepatic parameters including white blood cell (WBC), platelet (PLT), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCH), lymphocytes, neutrophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum Cu levels have been determined using their commercial kits. The results were analyzed in the SPSS software using t-test and regression method. Results: ALT, AST, HGB, MCV, MCH and plasma Cu levels among the workers were significantly higher than the office employees (p<0.050). WBC and RBC counts among the workers were significantly lower than the control group (p= 0.049 and 0.024, respectively). Serum Cu levels of 215 of the workers were higher than its normal recommended range (120 µg/dl). For the subjects with serum Cu levels above 150 µg/dl, increases in AST and ALT were in compliance with serum Cu levels increase. Conclusions: Significant hepatic and hematological alteration were observed among copper miners compared to control group. Employment of workers with background hematological and hepatic disorders in copper industries must be accompanied with great caution.

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Section: Discussionsupporting

confidence: 53%

Hematological and hepatic alterations among copper mine workers and office employees in a copper mine in the west of Iran, 2015

Lotfi

Rezazadeh

Ebrahimpour

2018

JOHE

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“…The use of antioxidants to supplement the treatment of patients suffering different pathologies that are associated to iron and/or copper overload and oxidative stress, such as Parkinson's and Alzheimer's diseases, is widely accepted. However, our data highlights the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders [40,41]. In view of our results, we believe, thiolbased antioxidants rather than polyphenol-based antioxidants could fulfill both the requirements.…”

Section: Resultsmentioning

confidence: 60%

Pro-oxidant DNA Breakage Induced by the Interaction of L-DOPA with Cu(II): A Putative Mechanism of Neurotoxicity

Perveen

Khan

Hadi

et al. 2014

Advances in Experimental Medicine and Biology

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There are reports in scientific literature that the concentration of copper ions in Parkinsonian brain is at a level that could promote oxidative DNA damage. The possibility of copper chelation by antioxidants excited us to explore the generation of reactive oxygen species (ROS) and DNA damage by the interaction of L-DOPA with Cu(II) ions. In the present manuscript, L-DOPA was tested for its ability to bind with Cu(II) and reduce it to Cu(I). The generation of ROS, such as superoxide anion (O(2)(-)) and hydroxyl radical (OH(•)), was also ascertained. As a result of L-DOPA and Cu(II) interaction, the generation of O(2)(-) was found to be increased in a time-dependent manner. Moreover, the formation of OH(•) was also found to be enhanced with increasing concentrations of L-DOPA. Furthermore, Comet assay results clearly showed significantly higher cellular DNA breakage in lymphocytes treated with L-DOPA and Cu(II) as compared to those that were treated with L-DOPA alone. However, such DNA degradation was inhibited to a significant extent by scavengers of ROS and neocuproine, a membrane permeable Cu(I)-specific sequestering agent. These findings demonstrate that L-DOPA exhibits a pro-oxidant activity in the presence of copper ions.

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“…Primary protein-oxidative effect of copper can be a consequence of protein-binding properties (Kato et al 2001). It has been shown that copper ions localize on the protein surface, primarily on cysteine residues, where prooxidant action of copper leads to oxidation of amino acid residues in protein molecule (Letelier et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Serum lipoprotein profile and oxidative stress biomarkers in Wistar rats fed drinking water containing iron and copper

Tinkov¹,

Nikonorov²

2013

Biologia

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The aim of the research was to estimate the effect of different doses and combinations of iron and copper consumption with drinking water on lipid profile and oxidative stress biomarkers in albino Wistar rats serum. Rats were given drinking water containing 3 mg L −1 and 6 mg L −1 iron; copper 4.88 and 9.76 mg L −1 ; a mixture of 3 mg L −1 iron and 4.88 mg L −1 copper. Control group obtained pure drinking water. Total cholesterol, lipoprotein spectrum and markers of lipid and protein oxidation were analyzed. It has been seen that administration of iron in concentration of 6 mg L −1 induces lipid peroxidation and protein oxidation, while copper given in the maximal doses leads only to protein oxidation. Free radical oxidation in rats obtaining combination of iron and copper with drinking water was more expressed than in case of administration of single metals in the same doses. Consumption of maximal doses of isolated metals leads to more expressed atherogenic changes, while combination of both metals in lower doses did not affect serum lipoprotein significantly. The data obtained show that chemical interaction of iron and copper in the organism has an additive effect on some vital parameters in comparison to isolated metal administration.

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Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects

Cited by 140 publications

References 30 publications

Hematological and hepatic alterations among copper mine workers and office employees in a copper mine in the west of Iran, 2015

Hematological and hepatic alterations among copper mine workers and office employees in a copper mine in the west of Iran, 2015

Pro-oxidant DNA Breakage Induced by the Interaction of L-DOPA with Cu(II): A Putative Mechanism of Neurotoxicity

Serum lipoprotein profile and oxidative stress biomarkers in Wistar rats fed drinking water containing iron and copper

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