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      Cytotoxicity of Titanate-Calcium Complexes to MC3T3 Osteoblast-Like Cells

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          Abstract

          Monosodium titanates (MST) are a relatively novel form of particulate titanium dioxide that have been proposed for biological use as metal sorbents or delivery agents, most recently calcium (II). In these roles, the toxicity of the titanate or its metal complex is crucial to its biological utility. The aim of this study was to determine the cytotoxicity of MST and MST-calcium complexes with MC3T3 osteoblast-like cells; MST-Ca(II) complexes could be useful to promote bone formation in various hard tissue applications. MC3T3 cells were exposed to native MST or MST-Ca(II) complexes for 24–72 h. A CellTiter-Blue® assay was employed to assess the metabolic activity of the cells. The results showed that MST and MST-Ca(II) suppressed MC3T3 metabolic activity significantly in a dose-, time-, and cell-density-dependent fashion. MST-Ca(II) suppressed MC3T3 metabolism in a statistically identical manner as native MST at all concentrations. We concluded that MST and MST-Ca(II) are significantly cytotoxic to MC3T3 cells through a mechanism yet unknown; this is a potential problem to the biological utility of these complexes.

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          Most cited references28

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          New trends for metal complexes with anticancer activity.

          Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in 'metals in medicine'.
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            Developing new metal-based therapeutics: challenges and opportunities.

            Unexpected side effects and problems experienced in clinical trials have created a difficult environment for those developing new pharmaceuticals and, as a consequence, the number of new chemical entities being registered has fallen to a historic low. Those developing metal-based therapeutics will face the same difficulties, but this environment also provides many opportunities for creative solutions to be applied to overcoming the problems and concerns. In this perspective, these challenges and opportunities are considered in the context of examples of a number of classes of metal-based therapeutics.
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              Clinical pharmacology of gold.

              Since the dawn of civilization, elemental gold and gold compounds have been revered and utilized by Shamen and medical practitioners alike for many varied pathological problems. In the 20(th) century following the observations of Jacques Forestier, injectable gold compounds were successfully used for the treatment of rheumatoid arthritis. Of the many compounds developed, gold sodium thiomalate has been the most extensively studied by basic scientists and by clinicians. In the1980s, the oral gold compound auranofin showed promise as a therapeutic contender to injectable gold, but the clinical side effect profile and fear of long term effects of immune suppression by auranofin, resulted in gold sodium thiomalate continuing as the preferred gold compound for rheumatoid treatment. However, the increased use and demonstration of effectiveness of low dose Methotrexate (MTX) in rheumatoid treatment over the last 20 years has resulted in a significant decline in the use of injectable gold sodium thiomalate, this despite the claims and evidence that it remains a useful agent in the management of rheumatoid arthritis. Several authors still contend that the injectable gold compounds can still play a valuable role, and indeed may be the correct first choice in the management of rheumatoid arthritis.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2016
                1 December 2016
                : 2016
                : 7895182
                Affiliations
                1Department of Restorative Dentistry, University of Washington School of Dentistry, Seattle, WA 98195-7456, USA
                2Savannah River National Laboratory, Aiken, SC 29808, USA
                Author notes
                *Yen-Wei Chen: ywchen@ 123456uw.edu

                Academic Editor: Wei-Jen Chang

                Author information
                http://orcid.org/0000-0003-1209-1168
                http://orcid.org/0000-0003-1287-0233
                http://orcid.org/0000-0003-3195-2197
                Article
                10.1155/2016/7895182
                5156824
                ecbe4a6b-299f-47e6-8613-f06e5bfb22e0
                Copyright © 2016 Yen-Wei Chen et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 October 2016
                : 6 November 2016
                : 9 November 2016
                Funding
                Funded by: Department of Restorative Dentistry at the University of Washington
                Funded by: United States Department of Energy
                Award ID: AC71713O
                Categories
                Research Article

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