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      Cell viability after simultaneous interactions of chromium(III) and iron(III)

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          Abstract

          Abstract. Background: Chromium(III) and iron(III) are essential elements playing a vital role in many cellular processes. The aim of the study was to investigate the effect of chromium chloride and iron chloride, used alone and in combination, on fibroblasts. Materials and methods: The BALB/3T3 cells were incubated with chromium chloride or iron chloride at concentrations of 50 – 800 µM. Moreover, chromium(III) and iron(III) were used in two combinations: 50 µM of chromium chloride plus 500 µM of iron chloride, and in the other case 500 µM of chromium chloride plus 50 µM of iron chloride. Cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction, Lactate dehydrogenase (LDH) release, and neutral red uptake (NRU) tests. Results: A dose-response decrease in cell viability was observed after incubating the BALB/3T3 cells with chromium chloride and iron chloride. It can be seen that mitochondria may be the first part of the cell to be affected by chromium(III). The disintegration of cell membrane and lysosomes follows mitochondria damage. Moreover, it can be concluded that cell membrane may be the first part of the cell to be affected by iron(III) toxicity. The disintegration of mitochondria and next lysosomes follows cell membrane damage. Moreover, the results suggest that chromium(III) at the concentration of 50 μM protects against iron(III) toxicity. The disintegration of mitochondria and next lysosomes follows cell membrane impairment. Moreover, the results suggest that chromium(III) at the concentration of 50 µM protects against iron(III) toxicity. Conclusion: Chromium(III) and iron(III) decrease cell viability. Chromium(III) at the concentration of 50 µM protects against iron(III) toxicity.


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          Most cited references16

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          The roles of iron in health and disease

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            Cytotoxicity and oxidative mechanisms of different forms of chromium.

            D Bagchi (2002)
            Chromium exists mostly in two valence states in nature: hexavalent chromium [chromium(VI)] and trivalent chromium [chromium(III)]. Chromium(VI) is commonly used in industrial chrome plating, welding, painting, metal finishes, steel manufacturing, alloy, cast iron and wood treatment, and is a proven toxin, mutagen and carcinogen. The mechanistic cytotoxicity of chromium(VI) is not completely understood, however, a large number of studies demonstrated that chromium(VI) induces oxidative stress, DNA damage, apoptotic cell death and altered gene expression. Conversely, chromium(III) is essential for proper insulin function and is required for normal protein, fat and carbohydrate metabolism, and is acknowledged as a dietary supplement. In this paper, comparative concentration- and time-dependent effects of chromium(VI) and chromium(III) were demonstrated on increased production of reactive oxygen species (ROS) and lipid peroxidation, enhanced excretion of urinary lipid metabolites, DNA fragmentation and apoptotic cell death in both in vitro and in vivo models. Chromium(VI) demonstrated significantly higher toxicity as compared with chromium(III). To evaluate the role of p53 gene, the dose-dependent effects of chromium(VI) were assessed in female C57BL/6Ntac and p53-deficient C57BL/6TSG p53 mice on enhanced production of ROS, lipid peroxidation and DNA fragmentation in hepatic and brain tissues. Chromium(VI) induced more pronounced oxidative damage in multiple target organs in p53 deficient mice. Comparative studies of chromium(III) picolinate and niacin-bound chromium(III), two popular dietary supplements, reveal that chromium(III) picolinate produces significantly more oxidative stress and DNA damage. Studies have implicated the toxicity of chromium picolinate in renal impairment, skin blisters and pustules, anemia, hemolysis, tissue edema, liver dysfunction; neuronal cell injury, impaired cognitive, perceptual and motor activity; enhanced production of hydroxyl radicals, chromosomal aberration, depletion of antioxidant enzymes, and DNA damage. Recently, chromium picolinate has been shown to be mutagenic and picolinic acid moiety appears to be responsible as studies show that picolinic acid alone is clastogenic. Niacin-bound chromium(III) has been demonstrated to be more bioavailable and efficacious and no toxicity has been reported. In summary, these studies demonstrate that a cascade of cellular events including oxidative stress, genomic DNA damage and modulation of apoptotic regulatory gene p53 are involved in chromium(VI)-induced toxicity and carcinogenesis. The safety of chromium(III) is largely dependent on the ligand, and adequate clinical studies are warranted to demonstrate the safety and efficacy of chromium(III) for human consumption.
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              Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms.

              Certain hexavalent chromium (Cr(VI))-containing compounds are recognized occupational human lung carcinogens and may pose an environmental health risk. The carcinogenicity of Cr(VI) is targeted to particulate forms of moderate to low solubility. Soluble Cr(VI) oxyanions in the immediate cellular microenvironment traverse the cell membrane by non-specific anionic transporters. Cr(VI) is reductively metabolized within cells by agents including ascorbic acid (Asc), glutathione (GSH) and cysteine (Cys). During Cr(VI) reduction, a diverse range of genetic lesions are generated including Cr-DNA binary (mono) adducts, Cr-DNA ternary adducts, DNA protein crosslinks (DPCs), bi-functional (DNA interstrand crosslinks (ICLs)) adducts, single-strand breaks (SSBs) and oxidized bases. Some forms of Cr damage, such as ICLs, present physical barriers to DNA replication/transcription and, thus, likely promote a terminal cell fate such as apoptosis or terminal growth arrest. Other lesions, such as ternary DNA adducts, are potentially pre-mutagenic. Cr(VI) exposure elicits a classical DNA damage response within cells including activation of the p53 signaling pathway and cell cycle arrest or apoptosis. Moreover, Cr(VI) also induces the ATM-dependent DNA damage response pathway which is paradoxically required for both apoptosis and survival after Cr(VI) insult. In yeast, moderately cytotoxic concentrations of Cr(VI) result in an initial G1 arrest and delayed S phase progression, whereas less toxic levels of Cr(VI) induce G2 arrest, which requires homologous recombination for exit and survival. The past several years has witnessed many important advances in our understanding of the genetic/cellular damage produced by exposure to Cr(VI). Further information is needed regarding the potential involvement of oxygen radicals in Cr genotoxicity, the specific DNA repair pathways activated by Cr and the complex signaling mechanisms involved in the cellular response to Cr(VI). These pertinent issues must be considered in relation to the potential role that each plays in the induction of human respiratory tract cancer by particulate Cr(VI) compounds.
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                Author and article information

                Journal
                Trace Elements and Electrolytes
                TE
                Dustri-Verlag Dr. Karl Feistle
                0946-2104
                May 24 2018
                Article
                10.5414/TEX01533
                0d70378d-20f1-43d3-b9b0-2ba9be559275
                © 2018
                History

                Endocrinology & Diabetes,General medicine,Medicine,Gastroenterology & Hepatology,Nutrition & Dietetics
                iron(III),chromium(III),cell viability

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